At the heart of the field sits electrospinning, the workhorse technique that dominates nanofiber production. In this process, a high voltage is applied to a polymer solution or melt, overcoming surface tension at the needle tip to form a Taylor cone. A charged jet then streaks toward a grounded collector, elongating and thinning as solvent evaporates, until continuous ultrafine fibers accumulate as a nonwoven mat. The technique is exquisitely sensitive: polymer concentration, viscosity, surface tension, and conductivity shape fiber formation, while applied voltage, flow rate, needle-to-collector distance, temperature, and humidity govern fiber diameter, beading, and porosity. Higher conductivity and moderate flow rates yield finer, smoother fibers, and careful control of ambient humidity can even introduce useful surface pores. Typical operating windows include voltages of 10 to 30 kilovolts, flow rates of 0.5 to 3 milliliters per hour, and working distances of 10 to 20 centimeters.

Electrospinning itself has diversified dramatically. Coaxial arrangements using two concentric nozzles generate core-sheath fibers in which a drug-rich core is protected by a functional shell, while multi-needle and needleless designs, including roller, wire, bubble, and corona systems, draw dozens of jets simultaneously from free liquid surfaces to raise throughput. Centrifugal spinning replaces electrostatic forces with mechanical ones for higher output, and variants such as melt, wet, AC, and near-field electrospinning offer solvent-free processing or sub-micron patterning precision. Beyond electrospinning, the review catalogs alternative routes: molecular self-assembly, in which peptides or small molecules spontaneously organize through hydrogen bonding and hydrophobic interactions into fibers just a few nanometers wide; phase separation, which uses polymer gelation and freeze-drying to produce nanofibrous matrices with tunable porosity; template-assisted extrusion through nanoporous anodic aluminum oxide membranes; and nanofiber printing, exemplified by 3D printing of carbon nanotube-dispersed nanofibrillated cellulose into aligned, conductive microfibers. Each method carries trade-offs in scalability, cost, and control over fiber architecture.

Material selection proves equally decisive. Natural polymers such as collagen, gelatin, chitosan, alginate, silk fibroin, and hyaluronic acid closely mimic the extracellular matrix, offering biocompatibility, low immunogenicity, and built-in cell-binding motifs, though they often suffer from weak mechanical strength and batch-to-batch variability. Synthetic polymers including polycaprolactone, polylactic acid, polyglycolic acid, PLGA, polyvinyl alcohol, polyethylene oxide, and polyvinylpyrrolidone provide predictable degradation rates, robust mechanical performance, and easy processing, enabling precise tuning of release kinetics. Hybrid systems combine the best of both, while functionalization with inorganic nanoparticles such as silver, zinc oxide, hydroxyapatite, gold, or magnetic iron oxide confers antimicrobial, osteoconductive, or stimulus-responsive behavior. Crosslinkers like genipin and EDC/NHS chemistry, plasma treatment, and silanization stabilize the finished fibers and anchor bioactive ligands.

How a drug gets into the fiber determines how it comes out. The review identifies four principal loading strategies. Blending dissolves the drug directly into the spinning solution, a simple one-step approach that works for hydrophilic and hydrophobic compounds alike. Encapsulation via coaxial or emulsion electrospinning shepherds delicate molecules into protective cores, with emulsion systems notably reducing first-hour burst release and improving the oral delivery of poorly soluble anticancer agents such as paclitaxel. Physical adsorption, the simplest method, relies on electrostatic and van der Waals forces to immobilize drugs on fiber surfaces, though weak binding limits in vivo reliability. Chemical immobilization through covalent linkages offers stronger, quantifiable attachment at the cost of added synthetic complexity. Release then proceeds through diffusion, dissolution, degradation, or swelling of the carrier, or through targeted mechanisms in which ligand-receptor pairing triggers drug delivery specifically at diseased tissue.

Perhaps the most striking advance highlighted is the rise of smart, stimuli-responsive nanofibers that release their payload only when prompted. pH-sensitive polymers exploit the acidic microenvironment of tumors and inflamed tissue; redox-cleavable bonds disintegrate under oxidative stress; thermo-responsive materials like poly(N-isopropylacrylamide) contract with temperature shifts; gold nanorods enable near-infrared light-triggered release; and superparamagnetic iron oxide nanoparticles generate local heat under alternating magnetic fields. Dual- and multi-responsive platforms now combine these triggers for unprecedented spatiotemporal control. Biomimetic designs go further, replicating the architecture of the natural extracellular matrix to simultaneously deliver drugs and direct cell behavior, with fiber alignment shown to steer cell shape, mechanotransduction signaling, and even metabolic phenotype, promoting myogenic differentiation and neurite outgrowth along aligned fibers.

Safety remains a central concern as these materials advance. Because of their nanoscale dimensions and enormous surface area, nanofibers can provoke cytotoxicity, genotoxicity, or inflammation depending on polymer chemistry, fiber dimensions, surface features, and degradation byproducts. Airborne fibers pose inhalation hazards during manufacture. The review stresses that standard metabolic assays such as MTT can be misleading on porous, high-surface-area scaffolds, where formazan crystals adsorb onto fiber surfaces, and recommends corroborating results with live/dead confocal staining, lactate dehydrogenase leakage assays, hemolysis testing, and flow cytometry. Long-term stability also demands attention: electrospinning can render crystalline drugs amorphous, improving solubility but risking recrystallization, while sterilization by ethylene oxide or gamma irradiation can fuse, degrade, or embrittle polymer fibers.

The clinical picture is brightening rapidly. In vivo studies demonstrate nanofiber matrices loaded with Exendin-4 improving rat tendon healing, propolis-infused silk fibroin gels closing full-thickness wounds by day 17, honey-based fibers achieving 94.3 percent healing in diabetic wounds, and radially oriented PLGA fibers releasing metformin for over 30 days in burn models. Nanofibers now serve as platforms for non-viral CRISPR activation, sustaining VEGF gene expression for three weeks and accelerating wound repair, and for localized AAV vector delivery enabling cardiac genome editing in mice. Commercially, products have already crossed the regulatory finish line: the nanofibrillar cellulose dressing FibDex, the self-assembling peptide hemostat PuraStat, and FDA-cleared orthopedic scaffolds such as Rotium wick and TAPESTRY are in clinical use, with trials also underway in dentistry, ophthalmology, and diabetic foot ulcer care.

Looking forward, the authors argue that artificial intelligence and 3D bioprinting will unlock truly personalized nanofiber medicine. Machine learning models, including support vector machines, artificial neural networks, and Gaussian process regression, are already predicting optimal electrospinning parameters, fiber diameter, encapsulation efficiency, and drug release profiles from existing datasets, slashing experimental iteration. Bioprinting enables patient-specific dosage forms, from self-dissolving vascular devices implanted in rat veins to polypill configurations for complex medication regimens. Major hurdles persist, chiefly scalable manufacturing, solvent residues, regulatory standardization, and the scarcity of human in vivo data, but the trajectory is unmistakable: nanofiber drug delivery systems, once a laboratory curiosity, are consolidating into a versatile, clinically validated platform poised to make treatment safer, smarter, and tailored to the individual patient.

Subject of Research: Nanofiber-based drug delivery systems for controlled and targeted therapeutic release

Article Title: A review of nanofiber-based drug delivery systems: fabrication, characterization, advances, and future prospects

Article References: Saleh, A. M., Selim, R. N., El-Morsy, M. T., Mansour, S. A., Elhady, R., Ismail, S. F. K., Gamal, M., & Kenawy, E.-R. S. (2026). A review of nanofiber-based drug delivery systems: fabrication, characterization, advances, and future prospects. Journal of Materials Science: Polymers, 1(1), Article 10. https://doi.org/10.1007/s44493-026-00009-2

Image Credits: AI Generated

DOI: 10.1007/s44493-026-00009-2

Keywords: nanofibers, drug delivery, electrospinning, controlled release, biomimetic materials, stimuli-responsive polymers, biocompatibility, 3D bioprinting, artificial intelligence, clinical translation, review, nanofiber-based