A team of pharmaceutical scientists in India has now developed a thin, flexible film loaded with amixicile, a next-generation antimicrobial, designed to be placed directly into the diseased gum pocket. The work, published in Discover Chemistry, describes how the researchers combined amixicile with two film-forming polymers, the natural polysaccharide pullulan and the synthetic, water-soluble polymer polyvinyl alcohol, to create a locally applied treatment for periodontitis. Amixicile is a derivative of the antiparasitic drug nitazoxanide and works through an unusual mechanism: it inhibits pyruvate-ferredoxin oxidoreductase, or PFOR, a key enzyme in the energy metabolism of anaerobic bacteria. By binding to thiamine pyrophosphate, a cofactor the enzyme depends on, amixicile prevents pyruvate from binding, blocking the formation of acetyl-CoA and carbon dioxide and thereby starving anaerobic pathogens of energy. Crucially, every oral Treponema species studied so far relies on PFOR, making amixicile a particularly promising candidate against periodontal pathogens, while its high selectivity for anaerobic organisms keeps it relatively non-toxic to host tissues.

The choice of polymers was equally deliberate. Pullulan, a fermentation product of the fungus Aureobasidium pullulans, is non-ionic, bio-erodible and biocompatible, with outstanding film-forming ability; it is already used in commercial oral care films sold internationally under the Listerine brand. Its many hydroxyl groups make it highly water-soluble, so it absorbs water, swells and breaks down, helping entrapped drug molecules diffuse out. Polyvinyl alcohol complements this by adding mechanical strength through intermolecular hydrogen bonding, improving the film’s elasticity, wettability and swelling behavior. Together, the two polymers form a matrix that is strong enough to be handled and inserted into a gum pocket yet dissolves quickly enough to release its payload. The films themselves were made by solvent casting: the polymers were dissolved in water, amixicile was stirred into the homogeneous blend, and the solution was cast into petri plates and dried in a hot air oven at 80 degrees Celsius before being trimmed into two-by-two-centimeter squares.

Before formulating, the team established how much drug is actually needed to stop microbial growth. Using a broth dilution method, they determined that the minimum inhibitory concentration of amixicile against both Pseudomonas aeruginosa and Candida albicans was 20 micrograms per milliliter. The minimum bactericidal concentration against Pseudomonas aeruginosa and the minimum fungicidal concentration against Candida albicans were both 25 micrograms per milliliter. The choice of test organisms reflects the complex ecology of periodontal pockets: Candida albicans is the most prevalent fungus in both healthy and diseased oral cavities and has been shown to facilitate invasion of gingival epithelial cells by Porphyromonas gingivalis, while Pseudomonas aeruginosa, though not a primary periodontal pathogen, can thrive in the low-oxygen niches of periodontal pockets, forming biofilms and secreting virulence factors such as phenazines and pyocyanin that sustain inflammation and tissue destruction.

To optimize the formulation rather than rely on trial and error, the researchers employed a central composite design, a statistical approach that systematically varies the concentrations of pullulan and polyvinyl alcohol and models their effects on two critical quality attributes: in-vitro drug release and tensile strength. Nine formulations were produced and evaluated. Drug content across the batches ranged from 87.7 to 97.4 percent, indicating that amixicile was evenly dispersed throughout the films. Drug release over five minutes ranged from about 81.8 to 95.2 percent, with formulations A1 and A6 performing best. The regression analysis revealed that both polymers increased drug release, but pullulan’s linear coefficient, 4.80, was nearly three times that of polyvinyl alcohol, 1.69, confirming that the hydrophilic polysaccharide was the dominant driver of dissolution. A low interaction coefficient showed the two polymers acted largely through their individual effects rather than synergistically on release.

Tensile strength told a complementary story. The strongest film, batch A1, withstood 12.8 newtons per square centimeter, a result attributed to high polymer concentrations producing dense chain entanglement and extensive hydrogen bonding. But excessive rigidity can compromise elasticity and patient comfort during periodontal application, so the strongest film was not necessarily the best. Batches with low polymer content, A2 through A5, ranged from just 1.02 to 5.23 newtons per square centimeter, reflecting weak matrix cohesion. Batch A6, with moderate polymer levels, achieved 10.78 newtons per square centimeter, striking what the authors describe as the ideal balance between structural stability and flexibility. The statistical models for both responses were validated by analysis of variance, with model F-values of 119.88 for drug release and 22.51 for tensile strength, and prediction errors for the optimized batch of only 0.41 percent for release and 2.13 percent for mechanical strength.

The optimized formulation, containing 300 milligrams of pullulan and 200 milligrams of polyvinyl alcohol, was then put through a full battery of characterization tests. The yellow film was uniform and smooth, with an average thickness of 0.06 millimeters, a weight of 0.0125 grams, and a folding endurance of 200 folds, indicating robust mechanical integrity. Its pH of 6 falls within the natural range of the oral cavity during gingival infections, minimizing irritation risk, and it disintegrated completely in about one minute, enabling rapid drug release. In-vitro diffusion through a cellophane membrane reached 78.6 percent over 70 minutes, notably longer than the five-minute release window, because only one side of the film contacted the membrane. When tested against fresh sheep gingival mucosa, ex-vivo diffusion reached 65.1 percent, with a steady-state flux of 0.93 micrograms per square centimeter per minute, about 16 percent lower than the in-vitro value, a reduction the researchers attribute to the additional diffusional and partitioning resistance of biological tissue.

Perhaps the most striking results came from the antimicrobial testing. Using an agar-well diffusion assay, the optimized film produced a zone of inhibition of 35 millimeters against Pseudomonas aeruginosa and 28 millimeters against Candida albicans. A plain pullulan film without drug showed much smaller zones, 18 and 22 millimeters respectively, meaning the drug-loaded film enlarged the inhibition zone by 94.4 percent against the bacterium and 27.3 percent against the fungus, differences that were statistically significant. The particularly large effect against Pseudomonas aeruginosa makes mechanistic sense, since that organism depends directly on the PFOR pathway that amixicile disables, whereas the eukaryotic fungus is affected through a less direct route. These findings suggest the film could suppress both the bacterial and fungal contributors to periodontal infection at the site where they do their damage.

The broader significance of this work lies in its approach to a stubborn clinical problem. Deep periodontal pockets, those exceeding four millimeters, are often inaccessible to thorough cleaning because of tooth structure, which is precisely why localized delivery systems that place antimicrobials directly at the infection site, prolonging drug contact time while limiting systemic exposure, have attracted so much research attention. A dissolvable film that releases over 95 percent of its drug within minutes, then sustains diffusion for over an hour, could offer clinicians a non-invasive, easy-to-insert option that avoids the resistance risks of systemic antibiotics. The authors are careful to note that the road to the clinic is not yet complete: preclinical periodontal efficacy testing, mucosal safety and toxicity studies, bioadhesion and residence time measurements, microbiological efficacy against clinically relevant periodontal organisms, and eventually clinical trials will all be required before therapeutic use can be established. Still, the convergence of a mechanistically novel antimicrobial, well-characterized biocompatible polymers, and rigorous statistical optimization makes this amixicile film a compelling candidate in the fight against a disease poised to affect billions.

Subject of Research: Development of an amixicile-loaded pullulan and polyvinyl alcohol composite film for localized drug delivery in periodontitis treatment

Article Title: Amixicile loaded polyvinyl alcohol and pullulan composite film for localized periodontal treatment

Article References: Kandekar, U., Davkare, P., Pandit, A., Chaudhari, P., Chavan, M., Sayare, A., & Kolhe, R. (2026). Amixicile loaded polyvinyl alcohol and pullulan composite film for localized periodontal treatment. Discover Chemistry, 3(1), Article 573. https://doi.org/10.1007/s44371-026-01011-x

Image Credits: AI Generated

DOI: 10.1007/s44371-026-01011-x

Keywords: amixicile, periodontitis, pullulan, polyvinyl alcohol, drug delivery film, PFOR inhibitor, antimicrobial, periodontal pocket, solvent casting, central composite design, Pseudomonas aeruginosa, Candida albicans

Proton-conducting polymer electrolytes are coveted for fuel cells, sensors, supercapacitors and batteries because they are flexible, leak-free and easy to process into thin films. The classic approach has been to soak acid-doped polymers such as poly(ethylene oxide), poly(acrylamide) or poly(vinyl alcohol) with proton sources, which does deliver respectable ambient-temperature conductivity, but at a cost. Acids attack metal electrodes and raise safety concerns, limiting practical devices. An alternative is to dissolve proton-donating salts directly into a polymer host, and among the most effective proton donors are ammonium salts with low lattice energy and bulky anions. The Indian duo chose ammonium thiocyanate, NH4SCN, a salt whose lattice energy of just 605 kilojoules per mole lets it readily fall apart in solution, releasing free ammonium ions that can then hop through a polymer network.

The choice of host polymer was equally deliberate. PVC is better known as pipe and window-frame material than as an ionic conductor, but its mechanical rigidity gives thin films structural stability, and its chlorine atoms carry lone pairs of electrons that help solvate and disperse inorganic salts. The missing ingredient was a way to open up the polymer’s tightly packed structure so ions could move freely. That is where strontium titanate came in. This perovskite ceramic, with particles measuring roughly 70.6 nanometers, brings exceptional thermal and chemical stability along with a large dielectric constant, properties that have made it attractive for high-frequency electrochemical applications. Reviews of the literature showed that PVC-based proton conductors with nanofiller additions had barely been explored, leaving a genuine gap for the team to fill.

Synthesis was disarmingly simple: the solvent casting technique. The researchers dissolved measured amounts of PVC and NH4SCN separately in tetrahydrofuran, stirred the solutions together for three hours to ensure homogeneity, then added varying weight percentages of the nano-sized strontium titanate and stirred again. The viscous mixture was poured into petri dishes and left in a vacuum oven at 60 degrees Celsius for 24 hours, yielding free-standing films ready for testing. All chemicals were used as received, meaning the recipe relies on nothing exotic, a point that matters for anyone hoping to scale the process beyond the laboratory bench.

The electrical results told a clear story. AC impedance spectroscopy, performed between stainless steel electrodes from 1 hertz to 10 megahertz, showed that the pristine PVC–NH4SCN film conducted at 5.233 × 10⁻⁸ S cm⁻¹ at room temperature. Adding 2 weight percent strontium titanate improved matters, but the real jump came at 6 weight percent, where conductivity peaked at 1.457 × 10⁻⁶ S cm⁻¹, nearly two orders of magnitude above the unfilled system. The mechanism is elegant: thiocyanate anions adsorb onto the nanoparticle surfaces, which suppresses ion-pair formation and drives greater dissociation of the ammonium salt into free, mobile ions. Beyond that optimal loading, however, the trend reversed. Excess nanoparticles aggregate into clumps that disrupt continuous ion-transport pathways, and the extra filler raises the mixture’s viscosity, throttling the polymer segmental motion on which ion hopping depends. The lesson is a familiar one in nanocomposite science: more filler is not better filler.

Temperature studies reinforced the picture. Conductivity rose steadily as films were heated, following the classical Arrhenius relationship, and the activation energy for ion migration dropped noticeably when strontium titanate was present. That reduction means ions need less energy to move through the matrix, which the team attributes to the growing amorphous content of the polymer. X-ray diffraction backed this up. Pure PVC showed Bragg peaks at 2θ values of 16.6 and 25.4 degrees, signature of partial crystallinity. When NH4SCN was blended in, the salt’s own sharp peaks vanished entirely, evidence that it had dissolved into the polymer to form a well-integrated complex. Adding strontium titanate then weakened the remaining diffraction intensity, confirming that the nanoparticles disrupt crystalline regions and create free volume, the open space that polymer chains and their hitchhiking ions need to move. Conductance spectra fitted to Jonscher’s universal power law showed a lower exponent for the best-conducting sample, indicating more available hopping sites for the charge carriers.

Differential scanning calorimetry added a thermal twist: the nanofiller behaves like a plasticizer. Pure PVC has a glass transition temperature near 90 degrees Celsius, and incorporating the salt nudged it to 86.66 degrees, with the ammonium ions forming transient cross-links that stiffen the chains. But at 6 weight percent strontium titanate, the glass transition fell to 76.95 degrees, meaning the nanoparticles weaken those constraints and restore chain flexibility, exactly what mobile ions need. The melting temperature of the optimally filled electrolyte was measured at 233 degrees Celsius, hinting at respectable thermal robustness. Dielectric measurements completed the diagnostic work-up: the dielectric constant grew with both filler loading and temperature, and the absence of relaxation peaks indicated that conductivity gains come from an increased density of mobile ions rather than from electrode effects. Wagner’s polarization technique put a number on the ionic dominance, measuring a total ionic transport number of 0.86 for the best film, confirming that charge is carried overwhelmingly by ions rather than stray electrons.

The payoff came when the team assembled an actual primary proton battery in a Teflon jig, sandwiching the 6 weight percent film between a zinc anode and cathodes of lead dioxide or vanadium pentoxide, with hydrated zinc sulfate supplying protons during discharge. At the anode, zinc oxidizes, donating electrons to the external circuit while zinc sulfate and water form; at the cathode, lead dioxide or vanadium pentoxide captures those electrons together with protons to yield metal ions and water. The cell delivered an open-circuit voltage of 1.16 volts that remained stable for up to 73 hours. Under a 1 megaohm load, the voltage initially sagged from 1.16 to 0.92 volts, an effect attributed to activation polarization at the electrode–electrolyte interface, and then settled onto a plateau that persisted for 79 hours, an unusually long discharge window for a lab-scale primary cell.

What makes the study compelling is not any single record-breaking number but the convergence of evidence across half a dozen independent techniques, from impedance spectroscopy and X-ray diffraction to dielectric analysis, thermal measurement and a working device. It demonstrates that an off-the-shelf plastic, a cheap ammonium salt and a well-known perovskite ceramic can be combined into a safe, acid-free, solid proton conductor with genuine battery performance. The durability of the open-circuit voltage over three days suggests the electrolyte–electrode interface is electrochemically quiet, a prerequisite for any practical energy-storage device. Challenges remain, not least that the peak conductivity of about 1.5 microsiemens per centimeter still trails the best acid-based systems, and scaling solvent casting to industrial widths will require engineering work. But the demonstration that strontium titanate simultaneously raises amorphous content, lowers activation energy, softens the polymer and boosts ion dissociation gives materials designers a clear, tunable knob. For a field hunting alternatives to corrosive proton conductors, humble PVC has just made a surprisingly strong case.

Subject of Research: Proton-conducting PVC nanocomposite polymer electrolytes modified with strontium titanate nanoparticles for primary proton battery applications

Article Title: SrTiO3-modified PVC nano composite proton-conducting electrolytes for primary proton battery applications

Article References: Jayanthi, S., & Muthuvinayagam, M. (2025). SrTiO3-modified PVC nano composite proton-conducting electrolytes for primary proton battery applications. Journal of Materials Science: Polymers, 1(1), Article 2. https://doi.org/10.1007/s44493-025-00002-1

Image Credits: AI Generated

DOI: 10.1007/s44493-025-00002-1

Keywords: solid polymer electrolyte, proton battery, PVC, strontium titanate, nanocomposite, ammonium thiocyanate, ionic conductivity, X-ray diffraction, glass transition temperature, dielectric constant, solvent casting, energy storage

Orally disintegrating films, or ODFs, are thin sheets that melt rapidly against the oral mucosa, releasing their payload for absorption without the need to swallow. Conventional ODFs rely almost exclusively on hydrophilic polysaccharides such as pullulan, hydroxypropyl methylcellulose, and pregelatinized starch, which disintegrate quickly; published examples include hydroxypropyl cellulose films that vanish in water in about 12.5 seconds and hydroxypropyl methylcellulose formulations that break down in roughly 43 seconds. But these matrices carry little nutritional value, and protein hydrolysate alternatives are prohibitively expensive. Soy protein isolate, a widely available and inexpensive plant protein with excellent film-forming ability and a rich amino acid profile, seemed like an obvious candidate, except that its dense, flexible molecular packing causes films to disintegrate sluggishly in water, sometimes lagging far behind their polysaccharide competitors.

The team’s answer was β-cyclodextrin, a cyclic oligosaccharide with a hydrophobic interior cavity and a hydrophilic, hydroxyl-covered exterior. Cyclodextrins are workhorses in food and pharmaceutical science, used to emulsify, solubilize, mask unpleasant flavors, and protect sensitive bioactive compounds. Previous work by some of the same authors had shown that β-cyclodextrin could accelerate the disintegration of soy protein films by disrupting the tight packing of protein chains. The new study asked whether the molecule could do double duty: remodel the protein network for rapid release while also protecting ergothioneine, a sulfur-containing antioxidant first isolated in 1909 from the fungus Claviceps purpurea and produced by edible fungi and cyanobacteria.

Ergothioneine was a demanding guest. Its unusually low redox potential of −60 millivolts makes it resistant to autoxidation, and studies have shown it outperforms glutathione at scavenging hydroxyl radicals, peroxyl radicals, and singlet oxygen. Yet antioxidant activity in ergothioneine-containing systems is known to decline during thermal processing and storage, likely through oxidative degradation. The researchers cast films by dissolving 2.0 grams of soy protein isolate in water at 75 degrees Celsius, adding 10 milligrams of ergothioneine, 0.7 grams of D-sorbitol as a plasticizer, and β-cyclodextrin at 0, 5, 10, and 15 percent of the dry protein weight, then drying the solutions in Petri dishes at 40 degrees Celsius for eight hours.

Microscopy revealed how dramatically the additive reshaped the material. The pristine soy protein film was rough and inhomogeneous, riddled with micropores and aggregated particulate domains, while adding ergothioneine alone smoothed the surface, apparently by promoting the unfolding of protein polypeptide chains. The real transformation came at 10 percent β-cyclodextrin, where the films displayed an extremely smooth, dense, defect-free surface organized into a continuous reticular network. The authors attribute this to hydrogen bonding between the cyclodextrin’s abundant hydroxyl groups and the protein network, which suppresses pore formation during drying. At 15 percent, however, the strategy backfired: bright, angular crystalline aggregates appeared across the surface, evidence that excess cyclodextrin had exceeded its solubility limit and phase-separated into β-CD-rich crystalline domains, shattering the structural continuity of the protein matrix.

Those structural changes translated directly into performance. The water contact angle, a measure of surface wettability, fell from 63.77 degrees in the control film to 36.28 degrees at 10 percent cyclodextrin, reflecting a far more hydrophilic surface that welcomes water penetration. Tensile strength climbed from 10.37 megapascals in the control to 12.15 megapascals at the optimal loading, and elongation at break rose from 3.462 to 4.376 percent, meaning the films became both stronger and more flexible. Then came the headline result: in vitro disintegration time dropped from 31.67 seconds in the control to 15.46 seconds at 10 percent cyclodextrin, a 45 to 52 percent improvement across the cyclodextrin-containing formulations, comfortably meeting the sub-60-second benchmark for fast-disintegrating films. Intriguingly, the 15 percent formulation showed no significant further gain, because its added thickness lengthened the path water had to travel, canceling out its extra hydrophilicity.

The loading data told a similarly encouraging story. High-performance liquid chromatography showed that ergothioneine loading efficiency rose from 66.83 percent in films without cyclodextrin to 76.33 percent at the 10 percent level, with loading capacity peaking at 2.16 micrograms per milligram of film. Relative standard deviations across replicate films stayed below 4 percent, confirming that the solvent casting method produces reproducible, uniformly dosed films. Each standard 15-by-15-millimeter dosing unit carried about 16.21 micrograms of ergothioneine in the optimal formulation. Surface pH values for all films ranged from 5.55 to 6.48, safely within the range tolerated by oral tissue, and mucoadhesive forces were essentially unchanged at moderate additive levels, reaching 0.69 newtons only in the phase-separated 15 percent formulation, where crystalline protrusions increased contact area.

The protective half of the dual function emerged under stress. The team sealed films in ordinary plastic bags and stored them for 28 days at 40 degrees Celsius, 75 percent relative humidity, under continuous fluorescent light to simulate accelerated oxidative aging. Films containing ergothioneine alone watched their DPPH radical scavenging activity collapse from 83.47 percent on day zero to 40.86 percent by day 28, with ABTS activity falling in parallel from 85.21 to 41.74 percent. Films with 10 percent cyclodextrin retained 60.57 percent DPPH activity and 60.68 percent ABTS activity over the same period, significantly better than every other formulation. Spectroscopic characterization supported the mechanism: X-ray diffraction showed the amorphous protein film acquiring the characteristic crystalline peaks of β-cyclodextrin, while Fourier-transform infrared spectroscopy revealed strengthened hydrogen bonding bands at 3288, 1641, and 1537 reciprocal centimeters, along with new peaks marking the cyclodextrin skeleton. Thermogravimetric analysis showed the maximum decomposition temperature rising steadily with cyclodextrin loading, from 300.28 degrees Celsius in the control to a peak of 314.63 degrees, confirming a more thermally robust composite.

The authors are careful about how far the interpretation can go. Because the antioxidant assays measure total radical scavenging of the entire film matrix rather than residual ergothioneine concentration directly, and because no inclusion complex between cyclodextrin and ergothioneine was demonstrated, the improved retention may reflect reduced oxidative exposure through intermolecular interactions and a denser matrix rather than the specific stabilization of individual ergothioneine molecules. The disintegration tests also used distilled water rather than simulated saliva, and all evaluations were in vitro. Future work employing HPLC or LC-MS quantification of ergothioneine, phase-solubility analysis, differential scanning calorimetry, and two-dimensional NMR is needed to pin down the molecular fate of the antioxidant during storage.

Even with those caveats, the implications are considerable. The study breaks the disintegration barrier that has kept soy protein out of serious consideration for orally disintegrating films, and it does so with a cheap, food-grade cyclodextrin that simultaneously improves mechanical strength, thermal stability, and antioxidant retention. For the food and pharmaceutical industries, the platform suggests a practical route to delivering sensitive bioactive compounds, from ergothioneine to other oxidation-prone nutraceuticals, in a fast-dissolving, plant-protein-based format that adds nutritional value instead of diluting it. If longer-term storage studies and in vivo safety testing bear out the accelerated results, the humble soybean may find itself at the leading edge of oral thin-film technology, one 15-second melt on the tongue at a time.

Subject of Research: Development of soy protein isolate-based orally disintegrating films using β-cyclodextrin to enhance disintegration and protect ergothioneine

Article Title: Development of soy protein isolate-based orally disintegrating films: The dual role of β-Cyclodextrin in enhancing disintegration performance and ergothioneine stability

Article References: Zhou, Y., Du, X., Lv, C., Tian, Y., Guo, S., Guo, Z., & Wang, Z. (2026). Development of soy protein isolate-based orally disintegrating films: The dual role of β-Cyclodextrin in enhancing disintegration performance and ergothioneine stability. Food Chemistry: X, 39, Article 104451. https://doi.org/10.1016/j.fochx.2026.104451

Image Credits: AI Generated

DOI: 10.1016/j.fochx.2026.104451

Keywords: orally disintegrating films, soy protein isolate, β-cyclodextrin, ergothioneine, oral drug delivery, antioxidant stability, film disintegration, hydrogen bonding, plant protein, Food Chemistry: X, bioactive compound protection, solvent casting