A bigel is, at its core, a marriage of two gels that normally want nothing to do with each other. One phase is a hydrogel, a network of plant-derived polymers such as proteins or polysaccharides swollen with water. The other is an oleogel, an oil continuous phase trapped inside a solid-like scaffold built from gelators such as waxes, ethylcellulose, or plant sterols. Because both phases are immobilized in their own networks, the resulting material behaves like a solid or semi-solid yet contains substantial water and oil simultaneously. That combination lets formulators replace solid fats in products like spreads, sausages, and bakery items while also using the two compartments as chemically distinct cargo holds: hydrophilic bioactives dissolve into the hydrogel, lipophilic ones dissolve into the oleogel, and neither needs a synthetic solvent to stay put.

The review’s central claim is that this biphasic architecture functions as a release-mechanism regulator rather than a passive container. Three canonical morphologies dominate the literature: oleogel-in-hydrogel, in which oil droplets gelled internally are dispersed through a polymer matrix; hydrogel-in-oleogel, the inverse arrangement; and bicontinuous systems in which both networks interpenetrate. Each geometry favors a distinct digestive trajectory. An oleogel-in-hydrogel design tends to shield the lipid phase behind a swelling polymer wall, delaying contact between dietary lipases and the oil until the bolus reaches the small intestine. A hydrogel-in-oleogel configuration instead embeds the water-based payload inside a fat continuous phase, which can protect water-soluble compounds from the acidic, protease-rich environment of the stomach. Bicontinuous morphologies, meanwhile, offer intermediate pathways whose release kinetics can be steered by tuning the connectivity of each network.

Underlying these broad patterns are specific physical mechanisms that operate during gastrointestinal transit. The review emphasizes that parameters such as the hydrogel-to-oleogel ratio, the density of the oleogel network, and the design of the interface between the two phases modulate how accessible pancreatic lipase and bile salts are to the lipid fraction. When lipase and bile salts reach the oil phase easily, lipolysis proceeds quickly and any lipophilic cargo is liberated early. When the oil is locked inside a dense crystal network or behind a robust interfacial film, lipolysis slows, and release shifts toward the intestinal phase where absorption is most effective. On the aqueous side, the swelling and erosion behavior of the hydrogel network governs how quickly hydrophilic compounds diffuse out, with crosslink density and polymer composition acting as the primary dials.

Across the studies the authors compared, two design rules emerged with unusual consistency. Denser oleogel networks and better-stabilized interfaces reliably slow lipolysis and push release into the intestinal stage, meaning bioaccessibility can be engineered rather than left to chance. Phase architecture, in turn, dictates which payload enjoys protection: the phase that surrounds the other determines whether a hydrophilic or a lipophilic compound is the one shielded from premature exposure. This reframing matters because traditional single-phase delivery systems force formulators to choose one protection strategy for all cargo. In a bigel, a single spoonful of a functional spread could, in principle, carry vitamin D in its oil phase and vitamin C in its water phase, each released on an independently controllable schedule.

Interfacial engineering adds a third, largely independent design dimension. The review highlights three strategies: Pickering stabilization, in which solid particles such as protein or cellulose nanocrystals adsorb at the oil-water boundary and form a physical barrier; amphiphilic gelators that self-assemble into interfacial films; and polysaccharide-layer modification, in which charged biopolymers are deposited onto droplet surfaces to thicken or strengthen the boundary. Because these interfacial layers control how fast lipase, bile salts, and co-solutes can penetrate, they let formulators decouple the release rate from the bulk gelator selection. A wax chosen for its melting profile or clean label status no longer locks in a single release behavior; the interface can be tuned separately to slow or accelerate lipolysis as the application demands.

These structural choices translate into measurable digestive performance. Reported applications show improved encapsulation efficiencies for both hydrophilic and lipophilic bioactives, reduced gastric pre-release of compounds that would otherwise degrade or be absorbed prematurely, and antioxidant synergism when co-encapsulated compounds regenerate or protect one another. The dual-network architecture also acts as a physical barrier against oxidation, since each gelled phase limits oxygen diffusion into the compartment holding its oxidation-sensitive payload. For plant-based food developers, the appeal is twofold: the same material that replaces saturated fat also serves as a delivery vehicle, collapsing two formulation problems into one ingredient.

The review is candid about the obstacles standing between laboratory prototypes and commercial deployment. The most significant is the absence of unified quantitative frameworks that predict release behavior from compositional inputs. Formulators currently cannot feed a bigel recipe into a model and obtain a reliable release curve; instead, each system must be characterized empirically. Compounding this, the field relies heavily on static in vitro digestion models that mimic the mouth, stomach, and intestine in sequential beakers but lack the mechanical shear, enzymatic renewal, and absorption dynamics of a living gut. Without in vivo validation, the review warns, reported bioaccessibility figures may not survive contact with real digestive physiology.

Standardization of characterization methods is a related concern the authors raise implicitly through their cross-study comparisons. Because different laboratories measure network density, interfacial coverage, and release kinetics with different protocols, pooling results across the plant-based literature is difficult, and design principles risk remaining qualitative. The review’s contribution is to organize the existing evidence into a structure-digestion framework, connecting specific formulation levers to specific digestive outcomes so that future studies can test hypotheses rather than rediscover patterns. Whether the community adopts shared benchmarks will determine how quickly the field can move from descriptive case studies to predictive design.

If those constraints are addressed, the authors argue, plant-based bigels could be systematically positioned for commercial deployment in functional foods, nutraceuticals, and pharmaceutical applications within the next decade. The vision is a new generation of plant-based products in which texture, nutrition, and delivery timing are designed together: a vegan cheese that releases vitamin B12 only in the intestine, a spread that protects polyphenols through the stomach, or a nutraceutical matrix that co-delivers fat-soluble and water-soluble actives on independent schedules. For a field long dominated by single-phase emulsions and hydrogels, the bigel’s two-network logic offers something rare in food science, a structural attribute that doubles as a control system, letting designers write the digestive itinerary of a nutrient before the food ever leaves the factory.

Subject of Research: Structural design and digestive behavior of plant-based bigels for controlled nutrient delivery

Article Title: Designing plant-based bigels for controlled nutrient delivery: structural and digestive perspectives

Article References: Shetty, P., Paulin Patricia, P., Sushmithasri, R., & Rawson, A. (2026). Designing plant-based bigels for controlled nutrient delivery: structural and digestive perspectives. Frontiers in Soft Matter, 6, Article 1888400. https://doi.org/10.3389/frsfm.2026.1888400

Image Credits: AI Generated

DOI: 10.3389/frsfm.2026.1888400

Keywords: food science, bigels, controlled release, nutrient delivery, soft matter, plant-based, gastrointestinal digestion, oleogel, hydrogel, functional foods, Designing, controlled

The central idea behind ultrasound-responsive drug delivery is elegantly simple. Microbubbles are gas-filled, shell-stabilized particles a few micrometers in diameter, originally developed as contrast agents for diagnostic imaging. When exposed to ultrasound waves, the encapsulated gas oscillates and eventually collapses through a phenomenon known as acoustic cavitation. If drug molecules are loaded into or onto the bubble shell, that collapse can eject or liberate the payload locally, creating a sharp temporal and spatial switch for drug release. In principle, a clinician could focus the ultrasound beam on a tumor and release the drug only within that volume, leaving healthy tissue—including the heart—largely unexposed to free cytotoxic agent.

What has often undermined this concept in practice is the way such formulations are developed. Traditional formulation work tends to proceed by trial and error, adjusting one variable at a time and hoping to stumble upon an acceptable product. The research team, led by Sonal Solanki and Nikunj Solanki together with collaborators across multiple Indian institutions, instead applied Quality by Design, or QbD, a systematic paradigm borrowed from pharmaceutical manufacturing science. QbD begins by defining a Quality Target Product Profile—the attributes the final product must possess—and then identifies critical quality attributes and the process and formulation parameters that control them. The result is a mathematical map relating input variables to product performance, allowing the formulator to operate deliberately within a proven design space rather than relying on luck.

Three formulation variables were selected as the critical factors to study: the concentration of chitosan, a biocompatible polysaccharide that forms the bubble shell; the concentration of palmitic acid, a fatty acid that likely stiffens and stabilizes the shell; and the concentration of Pluronic F68, a triblock copolymer surfactant widely used to modulate surface properties and stabilize emulsions. To explore how these three inputs interact, the team employed a Box–Behnken design, a response surface methodology that efficiently samples the experimental landscape with a manageable number of runs while allowing estimation of both main effects and quadratic interactions. The responses being optimized were microbubble size, doxorubicin encapsulation efficiency, and the burst release behavior triggered by ultrasound exposure.

The optimized formulation that emerged from the design space is notable for how tightly it threads the competing requirements. The microbubbles measure approximately 3.2 micrometers in diameter, small enough to behave well in vascular contexts yet large enough to respond vigorously to acoustic fields. Encapsulation efficiency reached approximately 70 to 75 percent, meaning that a substantial fraction of the expensive and toxic drug was successfully sequestered rather than floating free. Most importantly, when ultrasound was applied, more than 80 percent of the encapsulated doxorubicin was released within 40 seconds, while passive release under non-sonicated conditions remained low. That contrast between triggered and untriggered release is the pharmacological heart of the system: it means the drug is effectively caged until the operator decides otherwise.

The biological consequences of that gating were assessed in two cell lines chosen to represent the therapeutic target and the principal off-target risk. In MCF-7 breast cancer cells, the sonicated microbubble formulation—designated DOX-MB plus ultrasound—produced markedly greater cytotoxicity and apoptosis than either free doxorubicin or the microbubbles without ultrasound exposure. The numbers are striking. The apparent IC50, the concentration required to halve cell viability, was 0.0013 micrograms per milliliter for the sonicated formulation, compared with 0.62 micrograms per milliliter for free doxorubicin and 5.44 micrograms per milliliter for the loaded microbubbles left unsonicated. In other words, acoustic activation transformed a relatively weak cytotoxic preparation into one hundreds of times more potent than the free drug against the cancer cells.

A crucial experimental control strengthened the interpretation of those results. The researchers included a Blank MB plus ultrasound condition—microbubbles lacking doxorubicin that were subjected to the same acoustic exposure. This control produced only moderate bioeffects, confirming that cavitation alone does not account for the dramatic killing observed. The enhanced cytotoxicity of the complete system therefore reflects the synergy of two mechanisms working together: mechanical sensitization of the cells by oscillating and collapsing bubbles, and focal delivery of a high local dose of doxorubicin at the moment of collapse. Disentangling these contributions with appropriate controls is precisely the kind of rigor that empirical formulation studies often omit, and it lends credibility to the central claim that the system works as designed.

Just as important as what the bubbles do to cancer cells is what they fail to do to cardiac cells. In H9c2 cardiomyoblast cells, a widely used in vitro model of cardiac toxicity, the microbubble formulation without ultrasound showed reduced baseline toxicity compared with free doxorubicin, with an apparent IC50 of 8.72 micrograms per milliliter versus 5.14 micrograms per milliliter for the free drug. This shift indicates that sequestering doxorubicin within the bubble shell diminishes the drug’s availability to heart cells under normal, non-sonicated conditions—the very scenario that mirrors unintended exposure of cardiac tissue in a patient. The authors are appropriately careful here, describing their selectivity analysis as comparative in vitro indices and noting that the high selectivity value they calculated should be read as a trigger-dependent therapeutic window estimate rather than a conventional matched-condition selectivity index. That caveat reflects a genuine subtlety: the therapeutic window of this system depends on where and when the ultrasound is applied, not merely on intrinsic chemical selectivity.

The technical achievement of the QbD approach deserves particular emphasis. By quantifying how chitosan, palmitic acid, and Pluronic F68 concentrations jointly determine size, loading, and release kinetics, the study converts what is often a craft into a controllable engineering process. A formulator facing regulatory scrutiny can point to a defined design space within which product quality is assured, rather than defending a single recipe arrived at through opaque iteration. This matters especially for ultrasound-responsive systems, where subtle changes in shell composition can profoundly alter acoustic behavior, cavitation thresholds, and therefore both efficacy and safety. The constrained design space identified by the Box–Behnken model balances these competing demands explicitly, holding bubble size near the optimum for acoustic responsiveness while maximizing loading and triggered burst release.

The authors are candid that this work remains an in vitro proof of concept, and the path to the clinic is long. They specify that further acoustic calibration, testing in three-dimensional tumor models, hemocompatibility assessment, pharmacokinetic evaluation, biodistribution analysis, and in vivo tumor-localized ultrasound studies are all required before translational conclusions can be drawn. These are not trivial hurdles. Microbubble behavior in the bloodstream differs substantially from behavior in a culture dish, where bubbles and cells sit in immediate proximity. Blood flow, immune opsonization, bubble aggregation, and the physics of focusing ultrasound through tissue at depth all present real challenges. Hemocompatibility is a particular concern for any particulate system intended for intravascular use, and the interplay between acoustic parameters and tissue heating must be characterized to ensure that the ultrasound itself causes no harm.

Even so, the study offers a compelling demonstration of what rational formulation engineering can accomplish. Doxorubicin that is impotent until switched on by sound, and that spares heart cells when inert, addresses the two central failures of anthracycline chemotherapy in a single design. If subsequent in vivo work confirms that the sharp in vitro potency advantage and the attenuated cardiac exposure translate to living tumors, ultrasound-responsive microbubbles developed through QbD could move from an intriguing laboratory concept toward a genuinely controllable form of chemotherapy—one in which the clinician, not the drug, decides where and when the poison is released.

Subject of Research: Ultrasound-responsive doxorubicin-loaded chitosan microbubbles developed by Quality by Design for targeted breast cancer chemotherapy with reduced cardiac toxicity

Article Title: Ultrasound-responsive doxorubicin microbubbles engineered by QbD: enhanced in vitro anti-breast-cancer efficacy with attenuated cardiac cell toxicity

Article References: Solanki, S., Thota, S., Posa, M. K., Aphale, S., Kaul-Ghanekar, R., Pandey, S., Nagam, S. P., Kamble, S., Kulthe, A., Lalwani, K., Tailor, N. K., Sharma, R., & Solanki, N. (2026). Ultrasound-responsive doxorubicin microbubbles engineered by QbD: enhanced in vitro anti-breast-cancer efficacy with attenuated cardiac cell toxicity. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-026-01229-6

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01229-6

Keywords: doxorubicin, microbubbles, ultrasound-triggered drug delivery, Quality by Design, Box–Behnken design, breast cancer, cardiotoxicity, chitosan, MCF-7 cells, H9c2 cells, controlled release, nanomedicine

The work, led by Sanju Sarkar of BCDA College of Pharmacy & Technology in Kolkata and Bishal Sarkar of Mata Gujri College of Pharmacy in Bihar, addresses a persistent challenge in topical drug delivery. Conventional creams and gels containing metronidazole, a widely used nitroimidazole antimicrobial, often suffer from limited residence time at the application site, uncontrolled drug release, and the need for frequent reapplication. Nanogels offer a compelling alternative because their three-dimensional hydrated polymer networks can entrap drug molecules, control diffusion, and sustain release over extended periods, potentially improving therapeutic outcomes while minimizing systemic side effects.

Metronidazole itself is a well-characterized drug. Classified as a BCS Class I compound with a molecular weight of 171.15 grams per mole and a pKa of approximately 2.6, it is freely soluble in water and exhibits broad activity against obligate anaerobic bacteria and protozoa. Its mechanism of action relies on the intracellular reduction of its nitro group under anaerobic conditions, which generates reactive intermediates that damage microbial DNA and halt nucleic acid synthesis. This makes it a mainstay for treating dermatological, periodontal, gastrointestinal, and gynecological infections caused by anaerobic organisms, but its conventional topical formulations have not always delivered the sustained local concentrations clinicians would prefer.

Carbopol 940, a cross-linked poly(acrylic acid) polymer, was chosen as the nanogel scaffold because of its exceptional swelling capacity, bioadhesivity, biocompatibility, and gelling ability. When hydrated, it forms a three-dimensional network that absorbs water, modulates drug diffusion, and provides rheological properties well suited to topical application. The researchers hypothesized that varying the concentration of this polymer would alter the internal architecture of the gel matrix, and with it, the physicochemical characteristics, swelling behavior, particle size distribution, release kinetics, antimicrobial activity, and stability of the resulting nanogels.

To test this hypothesis, the team prepared three formulations, F1 through F3, using a homogenization-assisted polymer dispersion technique. Each contained 0.02 grams of metronidazole dissolved in propylene glycol, along with glycerol as a humectant and sodium benzoate as a preservative. The key variable was the amount of Carbopol 940: 0.01 grams in F1, 0.015 grams in F2, and 0.02 grams in F3. After dispersing the polymer in distilled water under magnetic stirring and allowing full hydration, the drug solution was added gradually, and the mixture was subjected to high-speed homogenization at 8000 revolutions per minute for one hour. Triethanolamine was then added dropwise to neutralize the formulation to the desired pH, and the nanogels were left overnight at room temperature to reach equilibrium.

Fourier transform infrared spectroscopy confirmed that metronidazole remained chemically compatible with Carbopol 940 throughout the formulation process. The spectra of the loaded nanogels retained the characteristic absorption peaks of both the drug and the polymer without any significant shifts, losses, or new peaks that would indicate chemical interaction or degradation. Peaks corresponding to aromatic C-H rocking vibrations, C-O stretching from the polyacrylic acid structure, and O-H stretching from the hydrated network all appeared as expected, providing strong evidence that the drug was successfully incorporated into the polymer matrix without structural compromise.

All three formulations emerged as homogeneous, smooth, pale yellow gels free of visible lumps, phase separation, and coarse particles. Their pH values ranged from 5.30 to 5.50, comfortably within the physiological range of approximately 4.5 to 6.5 for topical products, minimizing the risk of skin irritation. Drug content uniformity ranged from 94.70 percent in F1 to 99.94 percent in F3, with the higher polymer concentrations apparently enabling better drug entrapment within the hydrated network. Swelling indices followed a similar pattern, with F3 achieving the highest value at 33.00 percent, reflecting favorable interplay between polymer concentration and hydration of the cross-linked matrix.

Rheological testing revealed that all formulations exhibited pseudoplastic, shear-thinning behavior, meaning their viscosity decreased as shear force increased. This property is highly desirable for topical semisolids because it allows the product to flow easily during application yet maintain structural consistency at rest. At low rotational speeds, F1 and F3 showed viscosities of approximately 73,600 and 72,000 centipoise respectively, indicating robust polymer network formation. Dynamic light scattering measurements confirmed that F3 possessed the smallest average particle size at 143.4 nanometers, compared with 484.3 nanometers for F1 and 323.5 nanometers for F2, along with a zeta potential of −12.3 millivolts that suggested moderate electrostatic stability.

In vitro release studies conducted over eight hours using a diffusion cell with phosphate buffer at pH 7.4 revealed a biphasic profile for all three formulations. An initial burst release, attributed to drug molecules adsorbed on or near the surface of the hydrated matrix, was followed by a sustained release phase driven by diffusion through the swollen polymer network. F3 achieved the highest cumulative release of 97.03 percent at the eight-hour mark, outperforming F1 at 95.57 percent and F2 at 92.54 percent. Kinetic modeling showed that the zero-order model best described the release behavior, with F3 yielding the highest coefficient of determination at 0.997, indicating concentration-independent, controlled release. The Korsmeyer-Peppas model suggested anomalous, non-Fickian diffusion involving polymer chain relaxation and swelling effects.

Antimicrobial evaluation using the paper disc diffusion assay against Staphylococcus aureus and Escherichia coli produced strikingly asymmetric results. F3 generated significantly larger and more consistent zones of inhibition against S. aureus than the other formulations, while F1 produced no detectable zones at all under the experimental conditions. No formulation showed significant activity against E. coli, a result consistent with metronidazole’s known spectrum of activity against obligate anaerobes and the natural resistance of aerobic Gram-negative bacteria, whose outer membranes rich in lipopolysaccharides impede drug penetration. The researchers attribute F3’s superior performance against S. aureus to the synergistic effect of its small particle size, high swelling index, and sustained drug release, which together maintained prolonged local metronidazole concentrations near bacterial colonies during the agar diffusion test.

Subject of Research: Development and evaluation of metronidazole-loaded Carbopol 940 nanogels for topical antimicrobial drug delivery

Article Title: Carbopol 940-based metronidazole nanogels: formulation, physicochemical characterization, in vitro drug release, and antimicrobial evaluation

Article References: Sarkar, S., & Sarkar, B. (2026). Carbopol 940-based metronidazole nanogels: formulation, physicochemical characterization, in vitro drug release, and antimicrobial evaluation. Frontiers in Soft Matter, 6, Article 1912568. https://doi.org/10.3389/frsfm.2026.1912568

Image Credits: AI Generated

DOI: 10.3389/frsfm.2026.1912568

Keywords: metronidazole, Carbopol 940, nanogel, topical drug delivery, controlled release, antimicrobial activity, drug release kinetics, Staphylococcus aureus, polymeric network, pharmaceutical formulation, stability study, rheology

The scale of interest in plant natural products is striking. According to the review, PubMed listings for the phrase natural products have climbed to nearly 5,000 publications, up from 452 in the year 2000, and roughly a quarter of all medicines on the market trace their origins directly or indirectly to plant chemicals. Landmark examples include aspirin, derived from salicin found in willow species; quinine and artemisinin, isolated from Cinchona officinalis and Artemisia annua respectively; digoxin from Digitalis lanata; and the opium alkaloids morphine and codeine. Despite this rich history, delivering modern plant bioactives intact remains difficult because many secondary metabolites are highly sensitive to heat, light, oxygen, and pH swings, and compounds such as polyphenols often dissolve poorly in water, limiting absorption in the gut.

Encapsulation addresses these weaknesses by surrounding an active molecule with a thin protective coating of polymers, lipids, or biopolymers, in particles ranging from one to 1,000 micrometers for microsystems and one to 1,000 nanometers for nanostructures. The technique isolates the core material from environmental stress, can mask unpleasant flavors and colors, and permits release profiles that are delayed, sustained, or triggered by external cues. Nano-sized carriers add distinct advantages: their large surface area improves interaction with cells and biomolecules, and their small dimensions enhance cellular uptake and permit targeted delivery to diseased tissue. The review notes that recent clinical research has shown nano- and microencapsulation improving the pharmacokinetic and pharmacodynamic performance of curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, and berberine, with enhanced outcomes in vitro and in vivo models of cancer, neurodegenerative, cardiovascular, metabolic, and inflammatory disorders.

The authors catalog a broad toolkit of manufacturing techniques. Spray drying, in which a liquid feed is atomized into hot gas to yield dry powder particles, is widely used but exposes thermolabile compounds to temperatures between 170 and 220 degrees Celsius. Freeze-drying is gentler, and complex coacervation exploits electrostatic attraction between oppositely charged biopolymers, typically proteins and polysaccharides, to deposit a coating around droplets. Emulsification creates oil-in-water or water-in-oil dispersions stabilized by surfactant layers, and electrospinning and electrospraying use high-voltage electrostatic forces to stretch or break polymer solutions into nanofibers and nanoparticles under relatively mild conditions. The choice of wall material, whether lipids, natural polymers such as chitosan, zein, alginate, and whey protein, or synthetic polymers such as poly(lactic-co-glycolic acid), ultimately determines encapsulation efficiency, stability, and release behavior.

Among lipid-based systems, the review distinguishes solid lipid nanoparticles, which consist of a solid lipid core surrounded by a phospholipid monolayer, from the newer nanostructured lipid carriers, whose cores blend solid and liquid lipids to form a less organized crystalline matrix with higher loading capacity and reduced drug expulsion during storage. Liposomes, spherical vesicles built from phospholipid bilayers, can carry both hydrophilic and hydrophobic cargo and have already reached the most advanced stage of clinical translation, alongside polymer-based nanoparticles, with cancer therapy as the leading application. Resveratrol encapsulated in liposomes combined with a quorum-sensing molecule reduced tumor development in murine models by approximately 70 percent, and liposomal anthocyanins were protected against degradation by light, pH shifts, enzymes, and ascorbic acid.

Polymeric nanoparticles offer another versatile platform. Curcumin encapsulated in PLGA nanoparticles halted the formation of diabetic cataracts in an animal model, while a PLGA-based silymarin nanocapsule demonstrated sustained release, increased bioavailability, and selective toxicity against prostate cancer cells. Mucoadhesive coatings such as chitosan, which binds to negatively charged mucosal surfaces in the gastrointestinal tract, can substantially improve oral absorption of otherwise poorly bioavailable compounds. Nanoscale solid dispersions also dramatically change dissolution behavior: dispersing compounds in an amorphous form inside carrier matrices boosted the dissolution rate of naringin by 20 to 55 percent and of quercetin by as much as 100 times, and pectin-whey protein nanocomplexes achieved encapsulation efficiencies of 83 to 98.5 percent for D-limonene.

The review also highlights electrospraying as a particularly gentle technique for sensitive molecules. Free beta-carotene degraded completely within 180 minutes of ultraviolet exposure, whereas encapsulated beta-carotene lost only about 20 percent under the same conditions. Because electrodynamic processes operate without the high temperatures of conventional spray drying and accommodate both hydrophilic and hydrophobic compounds across a wide range of wall materials, the authors consider them inexpensive, adaptable, and promising candidates for scaled-up industrial production of nanomaterials.

Safety and regulatory questions loom large over the field. Nanotoxicity depends on particle size, shape, surface charge, composition, and dose, and nanoparticles can cross biological barriers and accumulate in the liver, spleen, kidneys, lungs, and brain, potentially provoking oxidative stress, inflammation, and cellular damage. Niosomes, vesicles formed from nonionic surfactants with typical encapsulation efficiencies between 10 and 40 percent and as high as 75 to 90 percent in optimized systems, are one alternative with high biocompatibility and low toxicity, and proniosomes, dry free-flowing precursors that form vesicles on hydration, were developed to counter aggregation and leakage. Despite encouraging clinical results with established nanoformulations such as Doxil, Abraxane, and Onivyde, the review stresses that no plant-derived phytochemical nanoformulation has yet received approval from regulatory bodies for commercial use, partly because standardized guidelines for characterization, toxicological evaluation, and environmental risk assessment remain incomplete.

Looking forward, the authors anticipate personalized delivery systems tailored to individual physiological conditions, disease states, and genetic profiles, alongside growth in stimuli-responsive and targeted nanocarriers capable of releasing payloads at specific sites. They call for comparative, standardized studies to identify the most efficient and scalable encapsulation methods, more in vivo and clinical trials to establish long-term safety and bioavailability, and cost-effective, environmentally sustainable manufacturing to ease the bottlenecks of process reproducibility, formulation stability, and batch-to-batch consistency that currently slow industrial translation. If those hurdles can be cleared, encapsulated plant bioactives could move from laboratory curiosity to value-added products with longer shelf life, greater efficacy, and controlled delivery, transforming how food, pharmaceutical, and nutraceutical industries harness the healing chemistry of plants.

Subject of Research: Micro- and nanoencapsulation of plant-based bioactive compounds to enhance their stability, bioavailability, and therapeutic activities

Article Title: Trends in micro and nanoencapsulation of various plant-based bioactive compounds for enhanced biological activities: a review

Article References: Gill, A. R., Sharma, P., Siwach, P., Garg, V. K., Bhosale, M. S., & Choudhary, R. K. (2026). Trends in micro and nanoencapsulation of various plant-based bioactive compounds for enhanced biological activities: a review. Frontiers in Nanotechnology, 8, Article 1839002. https://doi.org/10.3389/fnano.2026.1839002

Image Credits: AI Generated

DOI: 10.3389/fnano.2026.1839002

Keywords: nanoencapsulation, microencapsulation, phytochemicals, bioactive compounds, nanoparticles, lipid nanoparticles, liposomes, niosomes, controlled release, bioavailability, drug delivery, Frontiers in Nanotechnology

The review’s central argument is that multi-epitope vaccines are chemical products as much as immunological constructs. Once short antigenic peptide segments are stitched together with linkers, adjuvant sequences and carrier domains, the resulting molecule must survive formulation, storage, administration and biological transport. Peptide constructs frequently display unfavorable charge distribution, low aqueous solubility, excessive hydrophobicity, non-specific aggregation or susceptibility to proteases. Linkers intended to improve antigen processing can instead create new junctions, bury epitopes or introduce instability. A sequence that ranks highly in an MHC-binding predictor may therefore fail long before it reaches any immunological endpoint, and the authors insist that these chemical liabilities are part of the vaccine hypothesis itself, not a downstream inconvenience to be fixed later.

Nanocarriers enter the picture as chemically tunable systems that can partially rescue these liabilities. Polymeric nanoparticles built from poly(lactic-co-glycolic acid), chitosan or alginate offer biodegradable matrices and charge-based interactions, though they bring acidic degradation microenvironments, burst release and batch variability. Lipid-based systems, including the lipid nanoparticles that made messenger RNA vaccines possible, can encapsulate peptides and adjuvants while controlling membrane composition and PEG density, but cationic or ionizable formulations may raise reactogenicity and complement activation. Virus-like particles provide multivalent, repetitive antigen display, yet inserted epitopes can disrupt capsid assembly or reduce yield. Extracellular vesicles, a biologically derived platform, can display membrane-associated antigens and carry peptide or mRNA cargo, but they suffer from source-cell heterogeneity, variable cargo copy number and difficult purification. The review stresses that no carrier class is universally superior; performance emerges from the specific peptide-carrier-method combination.

Three primary studies cited in the review illustrate the prediction-to-formulation gap with unusual clarity. In the MS2 virus-like particle system, insertion of HIV-derived peptides into the wild-type coat protein disrupted capsid assembly entirely, and manufacturability was restored only through a single-chain dimer scaffold. In hepatitis B core virus-like particles carrying Toxoplasma gondii epitopes, four epitope combinations assembled and were immunogenic, but only one construct, HBcΔH82, improved both mouse survival and brain cyst burden, showing that display geometry rather than immunogenicity scores controlled protection. Conversely, the bioinformatically selected peptide rOmp22, a candidate against Acinetobacter baumannii, required chitosan-coated PLGA encapsulation to achieve roughly 55 percent encapsulation, sustained release and stronger protection than the free peptide. Together these cases span assembly failure, context-dependent translation and formulation rescue at distinct points of the same pipeline.

On the computational side, the authors assess the current generation of epitope predictors with measured skepticism. Tools such as NetMHCpan-4.1 and NetMHCIIpan-4.0 use neural-network ensembles trained jointly on binding-affinity and eluted-ligand data, offering broad allele coverage but weaker support for rare alleles and no direct model of T-cell receptor recognition. MHCflurry 2.0 separates affinity, antigen processing and presentation, improving mechanistic attribution for class I predictions, while BepiPred-2.0 provides scalable but conformationally limited B-cell epitope screening. Protein language models and structure-prediction systems such as AlphaFold add transferable sequence and structural representations, yet their embeddings are not calibrated vaccine endpoints and can propagate biases from training data skewed toward well-studied pathogens and common HLA alleles. Train-test leakage from homologous sequences can further inflate reported performance metrics.

The review proposes that epitope prediction be treated strictly as an upstream prioritization step, filtered through a two-stage developability gate. Candidates should first be ranked immunologically, then screened against intrinsic sequence descriptors including molecular weight, net charge, isoelectric point, hydrophobicity, aromaticity, aggregation propensity and protease-sensitive motifs. Only candidates within a predefined developability domain should proceed to context-dependent testing in the intended formulation. The authors argue that this prevents a high epitope score from overriding insolubility, aggregation or interface incompatibility, and they map each peptide liability to orthogonal analytical confirmation and explicit go or no-go decisions.

Formulation-oriented machine learning shows genuine but bounded promise. Wang and colleagues trained a LightGBM model on 325 mRNA-lipid nanoparticle formulations to predict immunoglobulin G titers and experimentally confirmed the resulting formulation ranking. Sato and colleagues used XGBoost to identify ethanol fraction, buffer pH and total flow rate as determinants of particle size and encapsulation efficiency, then applied Bayesian optimization to target lipid nanoparticles of approximately 80 and 200 nanometers. Kumar and Ardekani curated 6,454 lipid nanoparticle formulations from 21 studies and found descriptor-based ensemble models, particularly balanced random forest and extra trees classifiers, most accurate for predicting activity and cell viability. These successes, the review notes, demonstrate prediction of bounded quality attributes within a single platform, not proof that one model can optimize peptide nanovaccines across carrier classes.

Controlled release and biodistribution modeling represent the frontier where computational ambition most clearly exceeds current evidence. Classical kinetic models such as Higuchi, Korsmeyer-Peppas and Weibull remain useful but rest on assumptions that real nanocarriers strain through simultaneous diffusion, swelling, erosion, peptide-matrix binding and burst release. Physics-informed neural networks, which embed governing differential equations into neural-network training, could in principle connect sparse release data with mechanistic transport assumptions and estimate parameters that are difficult to measure directly. The authors treat this cautiously: if the governing physics is oversimplified or parameters are not identifiable, a physics-informed network can create the appearance of rigor without improving prediction. Similarly, physiologically based pharmacokinetic models borrowed from soluble small molecules cannot capture nanovaccine disposition, which involves injection-site depots, lymphatic transport, time-varying protein coronas and separate fates for carrier, intact peptide, degradation fragments and adjuvant.

The review’s conclusions are operational rather than celebratory. Future progress, the authors argue, depends less on isolated prediction accuracy than on standardized datasets, external validation, uncertainty quantification, reproducible experiments and chemically interpretable models. They propose a three-tier agenda: harmonized experimental protocols reported in FAIR-compliant formats; multiscale model integration linking release, degradation, lymphatic transport and immune timing through modular mass balances; and systematic sharing of negative data, including failed syntheses, aggregation, low loading and non-protective immune responses, which define platform boundaries and counteract publication bias. Their minimum end-to-end reporting framework requires that candidates advance only after passing predefined gates for peptide developability, interface compatibility, process robustness, intact release, pathway-specific antigen presentation and separate disposition of carrier, peptide and adjuvant, with uncertainty propagated at every stage.

The broader message for the field is a disciplined reframing of what artificial intelligence can and cannot yet do. AI has genuinely accelerated the nomination of candidate epitopes, and machine learning has delivered experimentally validated optimizations for lipid nanoparticle formulations. But the translation of predicted epitopes into chemically viable delivery systems remains the bottleneck, and it will not be solved by better binding predictors alone. The highest-impact work, Garcia-Atutxa and Villanueva-Flores conclude, will be the studies that connect immunological prediction with formulation chemistry, release kinetics, biodistribution and validation in a way transparent enough to be tested and reproduced. Until peptide solubility, aggregation, antigen orientation, corona-mediated masking and intact-antigen release are jointly represented in externally validated models, the chemical design of multi-epitope vaccine nanocarriers will remain a problem where chemistry, not computation, sets the pace.

Subject of Research: AI-supported chemical design of multi-epitope vaccine nanocarriers

Article Title: Artificial intelligence can support the chemical design of multiepitope vaccine nanocarriers

Article References: Garcia-Atutxa, I., & Villanueva-Flores, F. (2026). Artificial intelligence can support the chemical design of multiepitope vaccine nanocarriers. Discover Chemistry, 3(1), Article 469. https://doi.org/10.1007/s44371-026-00929-6

Image Credits: AI Generated

DOI: 10.1007/s44371-026-00929-6

Keywords: artificial intelligence, multi-epitope vaccines, nanocarriers, epitope prediction, peptide vaccines, lipid nanoparticles, controlled release, physics-informed neural networks, PBPK modeling, extracellular vesicles, machine learning, vaccine formulation

The problem the researchers set out to solve is a stubborn one in pharmacology. Hydrophilic, or water-loving, drugs diffuse rapidly away from an injection site, making it difficult to maintain therapeutic concentrations locally without exposing the rest of the body. This is especially dangerous for drugs with narrow therapeutic indices, where the difference between an effective dose and a toxic one is small. Existing platforms—implantable devices, hydrogels, polymeric microparticles, and conventional liposomes—each carry drawbacks, from the need for surgical implantation to complex chemical modifications that complicate manufacturing.

Liposomes, spherical vesicles made of lipid bilayers enclosing aqueous compartments, have long been favored carriers because they can encapsulate water-soluble drugs and present a diffusion barrier. The standard strategy has been to stiffen their membranes with cholesterol and saturated phospholipids possessing high phase-transition temperatures, on the theory that a less fluid membrane slows drug escape. Unsaturated lipids, whose double bonds introduce kinks into the acyl chains and lower the phase-transition temperature, were assumed to produce more fluid, more permeable membranes and therefore faster release and poorer encapsulation.

To test this assumption rigorously, the team compared liposomes made from phospholipids of identical 18-carbon chain length but varying numbers of double bonds, prepared under matched conditions with 28.6 mol% cholesterol. The model drug was tetrodotoxin (TTX), an ultrapotent local anesthetic that is extremely hydrophilic—its octanol/water partition coefficient logarithm is −4.44—and notoriously difficult to encapsulate, typically achieving only about 25% efficiency with passive loading. The results were striking: liposomes made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), which carries two double bonds, achieved roughly 72% encapsulation efficiency, about three times higher than the saturated DSPC formulation, with drug loading also threefold greater.

Release kinetics told an even more surprising story. In the first hour after preparation, only a small fraction of TTX escaped from DOPC liposomes—11-fold less than from the saturated DSPC version—while the four-double-bond DLPC formulation suppressed initial release 14-fold. Over seven days at body temperature, DOPC liposomes released just 1.3% of their TTX payload, roughly four times less than the saturated analogue. Because smaller particles release drug faster due to their higher surface area-to-volume ratios, and the unsaturated liposomes were in fact smaller, the effect could not be explained by size. The team also confirmed that direct chemical interactions between TTX and DOPC were absent by proton nuclear magnetic resonance spectroscopy.

The mechanism, revealed through cryogenic electron microscopy and confocal laser scanning microscopy, lay in ultrastructure. As the number of double bonds increased, the liposomes spontaneously reorganized from simple single-bilayer spheres into complex multilamellar and multivesicular (ML/MV) architectures—onions of nested membranes and vesicles-within-vesicles. A quantitative membrane area fraction, measured from fluorescently stained images, correlated almost perfectly (r = −0.99) with reduced one-hour release. A dithionite-quenching assay on fluorescently labeled liposomes independently confirmed the greater lamellarity of DOPC formulations, and liposomes made with negatively charged DOPG, which repel adjacent bilayers electrostatically and remain unilamellar, released drug nearly tenfold faster despite having the same degree of unsaturation.

The benefits extended broadly across hydrophilic molecules. Compared with saturated DSPC liposomes, DOPC formulations showed 1.6- to 3.3-fold higher encapsulation and loading for metformin, moroxydine, neosaxitoxin, the STING agonist 2′3′-cGAMP, the peptides insulin and teriparatide, and the protein interleukin-2, with one-hour release reduced 5- to 17-fold and seven-day release 2- to 9-fold slower. Notably, the more hydrophilic the molecule, the greater the advantage—consistent with the idea that each additional bilayer in the diffusion path presents a formidable barrier to water-soluble drugs. In contrast, the amphiphilic anesthetic bupivacaine, which can partition into and permeate lipid membranes, showed the opposite trend, releasing faster from more unsaturated liposomes.

The in vivo proof of principle came in a rat sciatic nerve block model, a demanding test because TTX is lethal at low doses if it escapes systemically. Free TTX at 5 micrograms was uniformly fatal, and saturated-liposome formulations at 110 micrograms produced only hours of block with signs of systemic spread. The DOPC liposomes, by contrast, delivered sensory nerve blockade lasting from 6.5 days at 80 micrograms of TTX to 13 days at 260 micrograms—50 times the lethal free dose—with no fatalities and essentially no contralateral deficits indicating systemic toxicity. When bupivacaine was co-loaded to accelerate onset, block was established within 30 minutes and lasted over eight days. Fluorescence imaging showed that both liposome types persisted at the injection site for weeks, confirming that the prolonged effect stemmed from slower release rather than slower clearance, and histology revealed inflammation and myotoxicity scores comparable to or better than the commercial liposomal bupivacaine product Exparel.

The implications reach well beyond anesthesia. A simple, injectable platform that passively achieves high loading and ultra-slow release of hydrophilic small molecules, peptides, and proteins—without covalent chemistry, aptamers, or device implantation—could transform sustained delivery of cancer immunotherapies like interleukin-2 and 2′3′-cGAMP, antiviral agents, and drugs for metabolic disease. The authors note that nanoscale extruded DOPC liposomes retained their ML/MV structure and sustained release, opening a path toward systemic applications. By reframing lipid unsaturation from a liability into an asset, the study suggests that some of drug delivery’s most stubborn constraints may yield not to more elaborate engineering, but to a reconsideration of the physics already hidden inside the lipid bilayer.

Subject of Research: Liposome-based sustained local drug delivery using unsaturated phospholipids

Article Title: Ultra-slow release of hydrophilic drugs via multilamellar–multivesicular liposomes formed by unsaturated phospholipids

Article References: Wang, Y., Xue, T., Torre, M., Han, Y., Shao, R., & Kohane, D. S. (2026). Ultra-slow release of hydrophilic drugs via multilamellar–multivesicular liposomes formed by unsaturated phospholipids. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-026-01793-6

Image Credits: AI Generated

DOI: 10.1038/s41551-026-01793-6

Keywords: liposomes, drug delivery, unsaturated phospholipids, DOPC, tetrodotoxin, multilamellar vesicles, local anesthesia, controlled release, hydrophilic drugs, nerve block, biomedical engineering, Nature Biomedical Engineering

The star of the study is a bio-metal-organic framework, or Bio-MOF, a class of crystalline materials in which metal ions are linked by organic molecules into extended, sponge-like networks. Unlike conventional MOFs built from petrochemical linkers, bio-MOFs use biologically derived building blocks. Here the researchers chose zinc ions coordinated by L-aspartate, an approach grounded in earlier crystallographic work on homochiral zinc aspartate frameworks that display multiple coordination modes. The resulting framework is inherently biocompatible in character, and zinc itself carries a reputation for skin-friendly and antimicrobial behavior, which makes the material attractive for textiles that touch human skin.

Gardenia yellow pigment, extracted from the fruit of Gardenia jasminoides, is prized in food and textile applications for its warm golden hue and its documented biological activities, including antioxidant and anti-inflammatory effects. Its weakness is chemical: the crocin and geniposide-derived chromophores that give the pigment its color are sensitive to pH swings, heat, and ultraviolet light. Previous stabilization strategies have included microencapsulation in alginate beads, inclusion complexes with beta-cyclodextrin, liposomal formulations, and coating with the zeolitic imidazolate framework ZIF-8. The new study extends this MOF-encapsulation strategy to an amino-acid-based host, testing whether a bio-MOF can do the same protective job with an even more benign composition.

The fabrication process relies on adsorption and encapsulation: the porous zinc L-aspartate framework acts as a molecular container, drawing gardenia yellow pigment into its cavities and holding it there as a solid hybrid material the authors call EGYP. The loading performance was striking. The team measured an adsorption-encapsulation efficiency of 86.15 percent, meaning the vast majority of the pigment offered to the framework ended up trapped inside it. That figure matters commercially as well as scientifically, because natural pigments are expensive relative to synthetic azo dyes, and any host that wastes less than fifteen percent of the payload during loading improves the economics of the process.

Encapsulation is only half the story; the pigment must also be recoverable when it is time to dye. The researchers found that the hybrid pigment behaves as a triggered-release system. In a 0.15 mol per liter sodium hydroxide solution, 55.06 percent of the loaded gardenia yellow was released from the EGYP host. The alkaline environment appears to weaken the interactions between the pigment molecules and the framework, allowing the colorant to diffuse back out into solution where it can interact with textile fibers. This pH-responsive behavior suggests a practical workflow: store and transport the pigment in a stable solid form, then liberate it in a controlled dyeing bath under alkaline conditions.

When the released pigment was applied to silk fibers, the results were encouraging on every metric the team evaluated. The dyed silk acquired a relatively uniform yellow shade, an important quality attribute since natural dyes are notorious for uneven, blotchy coloration that depends on mordant chemistry and bath conditions. More significantly, all of the evaluated color fastness ratings reached grade 3 or higher on the standard textile scale, indicating that the color resists washing and light exposure at a level acceptable for commercial fabrics. For a natural dye that degrades readily in its free form, achieving grade 3 or better fastness on delicate protein fibers like silk represents a meaningful technical milestone.

The hybrid approach delivered functional bonuses beyond color. The dyed silk showed antibacterial rates of 83.03 percent against Escherichia coli and 84.38 percent against Staphylococcus aureus, two benchmark organisms commonly used to assess antimicrobial textiles. The antioxidant activity of the dyed fibers reached 50.60 percent. These properties likely arise from a combination of the inherent bioactivity of gardenia yellow, which has been studied for pharmacological applications, and the zinc component of the framework, since zinc-based MOFs have previously been investigated for wound-healing dressings owing to antibacterial and anti-inflammatory behavior. A single dyeing step that imparts color, microbial resistance, and oxidative protection is an unusual and valuable combination for functional textiles.

The study sits within a broader research program by the same group on natural colorants and heritage conservation. The team has previously optimized tea stem dyes for silk, walnut green peel pigments for wool under microwave assistance, melanoidin microcapsules from Lycium barbarum residue for wool fabrics, and curcumin pigments stabilized by ZIF-8 for wool dyeing. They have also examined metal mordant binding mechanisms in historical silk using spectroscopic and computational analysis. The funding acknowledgments reveal the motivation: several grants support the conservation of excavated organic cultural relics in arid environments, including research on silk textile preservation from the Murong Zhi tomb of the Tuyuhun regime in the Tang dynasty. Understanding how to stabilize natural pigments on silk speaks directly to both modern sustainable dyeing and the preservation of ancient textiles.

The choice of an amino-acid linker also connects the work to environmental goals in the textile industry. Conventional dyeing of silk and wool relies heavily on synthetic dyes, heavy-metal mordants such as chromium and tin, and high water consumption, all of which carry environmental burdens. Bio-MOF hosts built from zinc and aspartate offer a route to pigments whose constituents are essentially nutritional and physiological in origin. The alkaline release step, while requiring chemical input, replaces the need for aggressive mordanting chemistry. If the release efficiency can be pushed higher and the process scaled, the approach could fit into the low-liquor-ratio, green printing and dyeing equipment technologies that the team’s affiliated institutions are separately developing for textile wastewater treatment.

Challenges remain before zinc aspartate hybrid pigments reach factory floors. The release efficiency of just over half means nearly half the loaded pigment stays locked in the framework during a single alkaline bath, and the fate of that residual material, whether it can be recovered, reused, or safely discarded, will need attention. Long-term light and washing fastness data, scalability of framework synthesis, and cost comparisons with established natural dye mordant systems will also determine commercial viability. Nevertheless, the demonstration that a bio-MOF can load gardenia yellow at over 86 percent efficiency, release it on chemical cue, and yield silk with grade 3 or better fastness plus antibacterial and antioxidant function marks a convincing proof of concept. It suggests that the next generation of natural dyes may not be liquids at all, but stable crystalline solids waiting in porous amino-acid cages until the moment of coloration arrives.

Subject of Research: Encapsulation of gardenia yellow pigment in a zinc L-aspartate bio-metal-organic framework for silk-fiber dyeing

Article Title: Fabrication of a zinc L-aspartate Bio-MOF-based hybrid pigment for silk-fiber dyeing

Article References: Wang, X., Liang, S., Zhang, D., Wei, Y., Ma, D., Wang, H., He, J., & Lei, Y. (2026). Fabrication of a zinc L-aspartate Bio-MOF-based hybrid pigment for silk-fiber dyeing. Journal of Materials Science. https://doi.org/10.1007/s10853-026-13811-8

Image Credits: AI Generated

DOI: 10.1007/s10853-026-13811-8

Keywords: bio-MOF, gardenia yellow pigment, silk dyeing, zinc L-aspartate, natural dyes, encapsulation, color fastness, antibacterial textiles, antioxidant activity, metal-organic frameworks, sustainable textiles, controlled release

The study, published in the journal Results in Chemistry, describes the design and characterization of a lipid nano-emulsion, abbreviated LNE-MP, in which L-DOPA is encapsulated within a blended lipid matrix. Lipid nano-emulsions belong to a broader family of lipid-based nanocarriers that have attracted intense interest in pharmaceutical science because they are biocompatible, biodegradable, and capable of hosting both water-loving and fat-loving drugs. What distinguishes the new work is its deliberate use of natural, sustainable lipid sources rather than synthetic excipients, and its systematic screening of the formulation variables that determine whether the resulting particles are small enough, uniform enough, and stable enough to be medically useful.

The underlying materials logic is elegant. A lipid carrier built purely from solid lipid tends to crystallize into a highly ordered lattice upon cooling, leaving little room for drug molecules to lodge inside. Incorporating a liquid lipid disrupts that ordered packing, creating structural imperfections and voids that can accommodate the drug during recrystallization. Myristic acid, a saturated fatty acid, was chosen as the solid component because it is biocompatible and forms a stable matrix after cooling, and because its free carboxylic group offers polar interaction sites for the hydroxyl, amino, and carboxyl functionalities of L-DOPA, favoring non-covalent drug-lipid association. Palm oil, a sustainable and cost-effective liquid lipid, was selected to supply the disordering fraction of the blend.

Manufacturing the particles involved two sequential steps. First, the lipid mixture, drug, and the nonionic surfactant Tween 80 were subjected to hot homogenization at 1500 revolutions per minute and 55 degrees Celsius for one hour, a temperature safely above the melting point of myristic acid. The resulting coarse emulsion was then refined by ultrasonication, with the team varying sonication time between 40 and 80 minutes and sonication power between 50 and 100 percent. Maltodextrin served as a drying adjuvant during spray drying, converting the liquid nano-dispersion into a structured, storable solid. The screening was conducted sequentially: first the ratio of myristic acid to palm oil was fixed, then surfactant concentration and ultrasonic parameters were tuned.

The ratio screening proved decisive for stability. Formulations with higher proportions of solid lipid, from a 5:5 blend down to 2:8, promoted particle aggregation and phase separation during thermal processing, while pushing the solid fraction below ten percent eroded the mechanical rigidity of the matrix and destabilized the dispersion once again. Only the 1:9 ratio of myristic acid to palm oil yielded a stable dispersion free of coagulation and phase separation after 24 hours of storage, striking the balance between matrix rigidity and liquid-lipid disorder that the colloidal stability of the carrier requires.

With the composition locked in, the processing variables revealed a clear hierarchy of influence. Raising the Tween 80 concentration from 1.5 to 2.0 percent had a more dramatic effect on particle size than any adjustment of sonication, driving the mean diameter from around 110 nanometers down to the 81 to 91 nanometer range. The surfactant lowers surface tension, stabilizing the spherical droplets formed during ultrasonic cavitation before they can recoalesce. The finest and most uniform product, with a mean size of roughly 85 to 86 nanometers and a polydispersity index as low as 0.10, emerged from the combination of 2 percent Tween 80, 80 minutes of sonication, and 50 percent power. Notably, excessive energy input was counterproductive: higher sonication power broadened the size distribution, because intense cavitation can fragment droplets only for them to remerge.

Characterization confirmed that the optimized particles were not merely small but colloidally robust. The zeta potential, a measure of surface charge, came in at approximately minus 40 millivolts, well beyond the minus 30 millivolt threshold generally associated with strong electrostatic repulsion between droplets and high physical stability in nanosuspensions. The negative charge arises from the ionization of acidic groups in the lipid components and the orientation of the nonionic surfactant at the particle surface, which generates an electrical double layer. In drug delivery, a moderately high negative surface charge carries a further advantage: it tends to reduce nonspecific protein adsorption and opsonization compared with cationic particles, potentially extending circulation time and improving biocompatibility.

Spectroscopy and microscopy filled in the molecular picture. Fourier transform infrared spectra of the loaded particles retained the characteristic aliphatic carbon-hydrogen stretches near 2920 to 2850 wavenumbers and the ester carbonyl band near 1740 to 1750 wavenumbers of the lipid matrix, indicating that the carrier’s chemical structure survived formulation intact. Meanwhile, the hydroxyl and amine bands characteristic of pure L-DOPA broadened and shifted in the loaded formulation, evidence that the drug’s functional groups engage in non-covalent interactions with the lipids. Crucially, no new absorption bands appeared, suggesting no chemical transformation of the drug within the sensitivity of the technique. Transmission electron microscopy showed nearly spherical particles with low aspect ratio and little clustering, consistent with the light-scattering data, while energy-dispersive X-ray spectroscopy detected only carbon, oxygen, and nitrogen, in approximate atomic proportions of 72, 25, and 3 percent, the nitrogen being the fingerprint of incorporated L-DOPA and the absence of other elements confirming high chemical purity.

Functionally, the formulation encapsulated roughly half of the initial L-DOPA payload, an efficiency the authors acknowledge will require further optimization if higher loading is pursued. The release behavior, however, is where the design shows its therapeutic promise. In dialysis-bag experiments conducted over eight hours, cumulative release climbed to about 27 percent at the intestinal pH of 7.4 and about 20 percent at the gastric pH of 1.2 after six hours, with no sudden burst release at either condition. The higher release at physiological pH reflects the differing solubility and ionization of L-DOPA and pH-dependent hydration of the particle surface. Kinetic modeling showed the profile fit a zero-order model best at pH 7.4, meaning release was governed more by the structural characteristics of the lipid carrier than by the remaining drug concentration, exactly the behavior desired for smoothing plasma fluctuations and reducing dosing frequency. The Korsmeyer-Peppas diffusion exponents fell in the anomalous transport range, though the authors treat that interpretation as preliminary given the model’s weaker fit.

The work remains at the in vitro stage, and the authors themselves note that chromatographic verification by high-performance liquid chromatography and additional solid-state studies by differential scanning calorimetry and X-ray diffraction are needed before the platform can advance. Even so, the demonstration that a sub-100-nanometer, narrowly distributed, electrostatically stabilized L-DOPA carrier can be built from myristic acid and palm oil, two cheap and abundant natural feedstocks, using nothing more exotic than homogenization and sonication, is a meaningful contribution to affordable nanomedicine. For a disease whose prevalence is rising steeply and whose patients depend on precise, steady dopaminergic dosing, a delivery platform that promises sustained release, reduced peripheral waste, and improved tolerability, manufactured from sustainable ingredients, offers a compelling glimpse of where Parkinson’s pharmacotherapy may be heading next.

Subject of Research: Lipid nano-emulsion formulation of myristic acid and palm oil for L-DOPA delivery in Parkinson's disease

Article Title: Efficient delivery of L-DOPA through lipid nano-emulsion formulation using solid myristic acid and liquid palm oil

Article References: Sardjono, R. E., Chyntia, A., Nuraini, V. A., Gunawan, R., Kadarohman, A., Ray, H. R. D., Vikasari, S. N., Erdiwansyah, Fatimah, S., & Ko, Y. G. (2026). Efficient delivery of L-DOPA through lipid nano-emulsion formulation using solid myristic acid and liquid palm oil. Results in Chemistry, 31, Article 103937. https://doi.org/10.1016/j.rechem.2026.103937

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103937

Keywords: L-DOPA, lipid nano-emulsion, myristic acid, palm oil, Parkinson's disease, drug delivery, nanoparticles, encapsulation efficiency, zeta potential, controlled release, Tween 80, sonication

The core idea is deceptively simple. Mesoporous silica nanoparticles, or MSNs, are tiny sponges of glass, typically tens of nanometres across, riddled with pores a few nanometres wide. Their enormous surface area, chemical stability and easily modified surface chemistry have made them favourites in drug delivery, and the same properties suit them to carrying corrosion inhibitors. The catch is that a sponge that leaks continuously wastes its cargo long before it is needed. Conventional coatings loaded with inhibitors suffer exactly this fate: the inhibitor leaches out steadily, depletes, and the coating loses its protective punch, forcing repeated maintenance. What the Italian team set out to build was a container that stays sealed in benign conditions and opens only when the local chemistry turns hostile.

To do this, the researchers synthesised two distinct nanoparticle architectures and compared them head to head. The first, dubbed MSNs-hex, was produced by a modified Stöber-like method using the surfactant CTAB as a soft template, yielding spherical particles of about 75 nanometres with neatly ordered hexagonal channels roughly 3 nanometres wide. The second, MSNs-CR, was grown in a biphasic oil-water system in which the silica precursor TEOS diffused slowly from a cyclohexane phase into the aqueous phase, producing flower-like particles of about 71 nanometres with a centre-radial, dendritic pore network spanning from micropores up to mesopores of 20 nanometres. Nitrogen adsorption measurements showed the hierarchical particles boasted a specific surface area of 750 square metres per gram, compared with 652 for the hexagonal particles, and a substantially larger pore volume.

That difference in architecture translated directly into cargo capacity. When the particles were loaded with benzotriazole, a classic and effective but environmentally problematic corrosion inhibitor, the hexagonal carriers took up roughly 1.3 percent of their weight, while the centre-radial particles absorbed about 6.5 percent, a fivefold improvement. The reason is geometric: the wide, branching channels of the hierarchical particles allow inhibitor molecules to penetrate deep into the interior rather than crowding near the pore mouths. For a delivery system intended to act as a concentrated reservoir in open environments where released molecules are rapidly diluted away, that deeper confinement is precisely the property that matters.

The second half of the design is the gate. The researchers functionalised the particle surfaces with pH-responsive polymers that change shape with acidity, physically plugging or unplugging the pores. Polyacrylic acid, or PAA, was grafted onto amino-functionalised particles through amide coupling. At strongly acidic pH around 2, hydrogen bonding coils the polymer chains into a collapsed state that seals the pore entrances; at neutral to alkaline pH, deprotonation of the carboxyl groups extends the chains, opening the pores. Dynamic light scattering and zeta-potential measurements confirmed this reversible conformational switching. In release experiments using Transwell chambers at 37 degrees Celsius, PAA-gated particles released more than 80 percent of their benzotriazole within the first 400 minutes at neutral pH, but only about 60 percent from the hexagonal particles and a mere 30 percent from the hierarchical particles at pH 2, where the gates stayed shut.

Kinetic analysis of the release data revealed a biphasic zero-order profile: a rapid initial burst of loosely bound inhibitor near the pore entrances, followed by a slower, sustained linear release of cargo confined deeper in the network. Notably, the hexagonal particles released a larger fraction of their modest load early on, because their narrow channels cannot accommodate much inhibitor deep inside, whereas the hierarchical particles acted as genuine slow-release reservoirs. For open corrosion systems, such as exposed bronze or cracked masonry where released inhibitor is continuously washed away, this sustained replenishment is the key to keeping local concentrations above the protective threshold.

Because concrete poses the opposite chemical problem, the team built a second gate for alkaline environments. Fresh concrete is highly alkaline, and corrosion of embedded steel begins when that alkalinity is lost or when chloride ions attack. Here the researchers turned to polyethylenimine, or PEI, a positively charged polyelectrolyte that was electrostatically assembled onto carboxyl-functionalised centre-radial particles. PEI remains protonated and pore-blocking at neutral pH but opens under alkaline conditions. The results were striking: PEI-gated particles released only about 40 percent of their benzotriazole at pH 7 over 72 hours, but nearly 90 percent at pH 11, the regime typical of concrete pore solutions. The apparent loading dropped from a remarkable 63.5 percent by weight before polymer grafting to roughly 7 percent after, a reduction the authors attribute to partial inhibitor loss during processing and to the diluting mass of the polymer layer itself.

Perhaps the most forward-looking element of the study is the substitution experiment. In place of benzotriazole, the researchers loaded caffeine, the familiar 1,3,7-trimethylxanthine of the coffee cup, as a green, bio-derived corrosion inhibitor. Caffeine adsorbs onto copper surfaces through its nitrogen- and oxygen-bearing functional groups, and previous studies have shown it can reduce copper corrosion in aqueous environments. The hierarchical particles took up 57.3 percent caffeine by weight, and after PEI gating the caffeine-loaded carriers displayed release profiles essentially indistinguishable from the benzotriazole system: about 40 percent at pH 7 and nearly 90 percent at pH 11. The lesson is that release behaviour is governed by the nanocarrier architecture and the polymer gate rather than by the identity of the cargo, meaning the platform can accommodate benign inhibitors without redesign.

To test whether controlled release translates into real protection, the team performed preliminary accelerated ageing experiments on bronze substrates at pH 11, examining the surfaces by optical microscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Uncoated bronze aged badly, with its oxygen content rising from 1.73 percent by weight in the unaged reference to 10.51 percent after exposure, a signature of heavy surface oxidation. BTA-treated bronze remained essentially pristine, with oxygen content of 1.82 percent, while caffeine-treated bronze showed an intermediate value of 4.22 percent, roughly 60 percent lower than the unprotected aged sample. The authors are careful to note that these surface-level measurements are not a substitute for full electrochemical corrosion testing, and that the protective gap between the two inhibitors reflects both the lower amount of caffeine retained and its weaker intrinsic interaction with the metal surface.

The broader significance of the work lies in its systems-level thinking. Rather than optimising a single variable, the study treats pore geometry, surface chemistry, polymer gating and inhibitor choice as a coordinated design space, matched to specific corrosion scenarios: PAA gates for acidifying open environments, PEI gates for alkaline concrete, hierarchical pores for maximum reservoir capacity. The high surface area, tunable porosity and robust silica framework also make these particles compatible with incorporation into polymeric, sol-gel and cementitious matrices, paving the way for coatings that combine passive barrier protection with on-demand active chemistry. If subsequent electrochemical validation and flow-condition testing bear out the promise, the humble coffee molecule, delivered by a nanoscale sponge that knows when to open, could become a serious weapon in the multibillion-dollar fight against corrosion, extending the life of infrastructure and cultural heritage alike while easing the environmental burden of the toxic inhibitors we rely on today.

Subject of Research: pH-responsive mesoporous silica nanocarriers for controlled corrosion-inhibitor release

Article Title: Pore-engineered mesoporous silica nanocarriers for sustainable, stimuli-responsive corrosion-inhibitor release

Article References: Mastrorilli, M., Rizzi, F., Lasala, P., Grandolfo, A., Eramo, G., Olivieri, F., Castaldo, R., Gentile, G., Lavorgna, M., Depalo, N., Fanizza, E., & Curri, M. L. (2026). Pore-engineered mesoporous silica nanocarriers for sustainable, stimuli-responsive corrosion-inhibitor release. Journal of Materials Science. https://doi.org/10.1007/s10853-026-13748-y

Image Credits: AI Generated

DOI: 10.1007/s10853-026-13748-y

Keywords: mesoporous silica nanoparticles, corrosion inhibition, pH-responsive polymers, benzotriazole, caffeine, hierarchical porosity, polyacrylic acid, polyethylenimine, smart coatings, cultural heritage conservation, concrete infrastructure, controlled release

The bacterium at the heart of the study was not chosen at random. The team isolated eleven endophytic bacterial strains from surface-sterilized guava roots collected in Una district, Himachal Pradesh, and screened them for the classic toolkit of plant growth promotion: indole-3-acetic acid production, phosphate solubilization, siderophore secretion, hydrogen cyanide production, and antagonism against fungal pathogens. One isolate, designated U35, consistently outperformed the rest, solubilizing 342.20 micrograms of phosphate per milliliter, producing 93.10 micrograms per milliliter of the auxin IAA, and inhibiting the growth of Fusarium oxysporum by 57.67 percent and Rhizoctonia solani by 61.33 percent. Sequencing of its 16S rRNA gene, submitted to GenBank under accession number PX919715, placed the isolate in the genus Serratia, a group increasingly recognized for its dual talents as a growth promoter and a biocontrol agent.

Free-living inoculants, however, face a hostile world once they leave the fermenter. Introduced cells must compete with established soil microbes, endure temperature swings and desiccation, and survive months of transport and storage before they ever encounter a root. The standard answer to this problem is microencapsulation, the immobilization of viable cells within a polymer matrix that shields them from stress and meters out their release over time. Sodium alginate, a gel-forming polysaccharide derived from brown algae, is the workhorse material for this purpose because it is biodegradable, non-toxic, inexpensive, and gels under gentle room-temperature conditions. But plain alginate beads are porous and prone to cracking, which compromises both their mechanical integrity and the protection they afford.

The Indian team’s solution was to reinforce the alginate with two additives. Corn starch acts as a filler that reduces shrinkage and porosity, maintains the sphericity of the beads, and improves bacterial viability during drying and storage. Chitosan nanoparticles, particles of a deacetylated chitin derivative measuring 80 to 100 nanometers, bring biocompatibility, film-forming ability, and antimicrobial properties to the matrix. Crucially, the researchers found that the nanoparticles’ effect on the encapsulated bacterium is concentration dependent. At 25 micrograms per milliliter, chitosan nanoparticles showed no inhibitory effect on Serratia sp. ABU35, but at 100 to 200 micrograms per milliliter they produced clear zones of bacterial killing, with the largest inhibition zone, 21.33 millimeters, appearing at the highest concentration. That dose-response relationship dictated the formulation: 25 micrograms per milliliter was the sweet spot at which the nanoparticles could improve the matrix without massacring its cargo.

The capsules themselves were made by ionic external gelation, a technique in which a sterile solution of 2 percent sodium alginate, 2 percent corn starch, and the nanoparticle suspension is mixed with a concentrated bacterial suspension and dripped into calcium chloride. Calcium ions cross-link the alginate into a gel network within 30 to 45 minutes, trapping the cells inside ovoid to near-spherical beads roughly 100 micrometers in diameter. Field emission scanning electron microscopy revealed smooth surfaces with minor irregularities that the authors suggest may actually aid bacterial immobilization and controlled release. Fourier transform infrared spectroscopy confirmed the chemical integration of all three components, showing the overlapping hydroxyl and amine stretching bands expected of a composite, while X-ray diffraction demonstrated that the sharp crystalline peaks of the individual polymers broadened and attenuated in the composite, indicating a predominantly amorphous structure, a property generally associated with better solubility and release behavior.

Performance testing showed that the optimized formulation, dubbed AlgSC, excelled on every metric the team measured. Encapsulation efficiency reached 99.23 percent, a 6.39 percent improvement over plain alginate beads. The swelling ratio climbed to 156.67 percent and moisture content to 78.33 percent, both the highest among the formulations tested, reflecting the hydrophilic character that starch and chitosan impart to the matrix. When beads were immersed in saline for sixty days, viable cells leaked out slowly at first, reached roughly 10 to the sixth CFU per milliliter by day ten, surged to 10 to the eleventh by day forty, and then stabilized near 10 to the eighth CFU per milliliter. Fitting the data to standard release models revealed a biphasic pattern best described by zeroth-order kinetics, meaning the bacteria emerged at a nearly constant rate independent of the remaining cell population, exactly the behavior a slow-release agricultural product should exhibit.

Shelf life was the study’s headline achievement. After twelve months at 4 degrees Celsius, the encapsulated bacteria retained 8.94 log CFU per gram, a survival rate of 75.19 percent, and even at room temperature they maintained 5.66 log CFU per gram, surviving at 43.98 percent. Free cells fared far worse: liquid cultures lost most of their viability within months, retaining only 19.44 percent survival after nine months in the refrigerator and 40.74 percent after just three months at ambient temperature. Just as importantly, the encapsulated cells kept their functional talents. After a full year in storage, the immobilized bacteria still produced 47.85 micrograms per milliliter of IAA, compared with 30.50 for free cells, and continued to form visible halos of phosphate solubilization on Pikovskaya medium. Antifungal activity also persisted, with the encapsulated formulation inhibiting F. oxysporum by 49.33 percent and R. solani by 53.33 percent, modestly below the liquid culture but still substantial.

The real test came in the greenhouse. In a one-year pot trial at Dr. Y.S. Parmar University of Horticulture and Forestry, six-month-old guava plants received either nothing, a full recommended dose of chemical fertilizer, liquid Serratia culture, encapsulated bacteria without nanoparticles, encapsulated bacteria with nanoparticles, or a combination of liquid and encapsulated inoculant. Every growth parameter responded significantly to the encapsulated treatment. Compared with untreated controls, plants given the nanoparticle-loaded capsules showed 125.26 percent greater shoot length, 83.75 percent greater root length, 92.32 percent greater shoot biomass, 158 percent greater root biomass, 136.08 percent greater plant height, 104.71 percent greater leaf area, and 142.86 percent more leaves. Against the liquid culture treatment, the encapsulated formulation delivered further gains of 21 to 49 percent across the measured traits, and plants receiving capsules containing chitosan nanoparticles outperformed those given nanoparticle-free capsules by 21.03 percent in shoot biomass and 30.45 percent in root biomass. The best overall results came from combining the liquid and encapsulated forms, an outcome the authors attribute to free cells colonizing the rhizosphere quickly while the capsules sustain the population over time.

The soil itself changed under the treatment. Rhizosphere soil from plants given the combined inoculant recorded the highest levels of total nitrogen at 428.45 kilograms per hectare, available phosphorus at 47.40 kilograms per hectare, and available potassium at 346.33 kilograms per hectare, along with the largest populations of bacteria, fungi, and actinomycetes. Dehydrogenase activity, a proxy for overall microbial metabolism, rose from 2.47 to 3.14 micrograms of triphenyl formazan per gram of soil, and phosphatase activity climbed from 6.30 to 8.61 micrograms of p-nitrophenol per gram, while urease activity remained statistically unchanged. Principal component analysis confirmed that the encapsulated treatments separated cleanly from the control and fertilizer-only groups, with the first two components explaining 99.87 percent of the variation in growth attributes.

The authors are careful to note the limits of their evidence. The pot trial used sterilized soil, an artificial environment stripped of the native microbial competition that inoculants face in real orchards, and all results come from controlled conditions rather than open fields. Field validation will be needed before the capsules can be promoted as a genuine alternative to synthetic fertilizer for guava, a crop that ranks fourth in cultivated area in India and is prized as a nutritional powerhouse rich in vitamins A and C. Still, the study demonstrates something rare in biofertilizer research: a formulation that solves the shelf-life problem in a single, elegant materials-engineering step, preserving both the viability and the functional repertoire of a beneficial bacterium for a full year. If the greenhouse promise survives contact with real soil, nanoparticle-reinforced biopolymer capsules could become a standard delivery vehicle for the next generation of microbial crop inputs.

Subject of Research: Encapsulation of the endophytic bacterium Serratia sp. ABU35 in a sodium alginate-corn starch-chitosan nanoparticle matrix for controlled-release biofertilizer delivery in guava

Article Title: Development of an encapsulated biofertilizer using a sodium alginate-corn starch-chitosan nanoparticle matrix for improved shelf life and controlled delivery of Serratia sp. ABU35 to enhance growth performance of guava (Psidium guajava L.)

Article References: Kalotra, S., Chauhan, A., Thakur, M., Tomar, M., & Kumar, G. (2026). Development of an encapsulated biofertilizer using a sodium alginate-corn starch-chitosan nanoparticle matrix for improved shelf life and controlled delivery of Serratia sp. ABU35 to enhance growth performance of guava (Psidium guajava L.). Discover Plants, 3(1), Article 423. https://doi.org/10.1007/s44372-026-00891-8

Image Credits: AI Generated

DOI: 10.1007/s44372-026-00891-8

Keywords: biofertilizer, Serratia sp. ABU35, microencapsulation, sodium alginate, chitosan nanoparticles, corn starch, guava, plant growth-promoting bacteria, shelf life, controlled release, soil health, sustainable agriculture