Only a tiny fraction of an eye drop ever reaches the tissue it is meant to treat. According to a spotlight article published in AAPS Open, topical ocular drug delivery remains one of the most stubborn problems in pharmaceutics because the eye is built to expel foreign substances quickly. Tear turnover, drainage through the nasolacrimal duct, blinking, and tight epithelial barriers all conspire to limit how long a drug stays on the ocular surface and how much of it is absorbed. The result is striking: just 1 to 7 percent of a topically administered dose reaches intraocular tissues, with the rest washed away or shed before it can act.
That inefficiency matters most for drugs that are already chemically difficult. One example highlighted in the article is indomethacin, a nonsteroidal anti-inflammatory drug used in conjunctivitis, uveitis, and postoperative inflammation. Indomethacin suffers from poor aqueous solubility and limited corneal permeability, two properties that make it a poor fit for the eye’s rapid-clearance environment. The article argues that an effective ocular delivery system must therefore solve several problems at once: enhance solubility, prolong residence time on the eye, and enable sustained release rather than the brief pulse delivered by conventional drops.
The researcher at the center of the spotlight, Alaa Y. Darwesh, is a PhD candidate in the Pharmaceutical Engineering and 3D Printing (PharmE3D) Laboratory at the University of Mississippi’s Department of Pharmaceutics and Drug Delivery, supervised by Professor Mohammed Maniruzzaman. She also serves as an Assistant Lecturer in the Department of Pharmaceutics at Mansoura University in Egypt. Her work sits at the intersection of pharmaceutical cocrystal science, electrospinning, medical imaging, 3D printing, and hybrid advanced manufacturing, targeting ocular, nasal, oral, vaginal, and radiopharmaceutical delivery routes.
A central tool in her approach is pharmaceutical cocrystallization, a solubility-engineering strategy that improves the physicochemical properties of poorly soluble drugs without altering their pharmacological activity. Cocrystals form through noncovalent interactions between an active pharmaceutical ingredient and a pharmaceutically acceptable coformer, producing a new crystalline phase with enhanced solubility, dissolution rate, and stability. The indomethacin–saccharin cocrystal is a well-established system in this field, demonstrating approximately twofold higher solubility than pure indomethacin, according to the article, which cites work by Tanaka and colleagues.
Cocrystals are not merely a laboratory curiosity. The article points to clinically approved oral products that incorporate pharmaceutical cocrystals, including Entresto (sacubitril–valsartan) and Steglatro (ertugliflozin), as evidence of the approach’s translational potential. In these formulations, cocrystallization is used to enhance solubility, dissolution, bioavailability, and solid-state processability without changing therapeutic activity. Yet integrating preformed cocrystals into final dosage forms remains difficult, typically requiring multi-step manufacturing processes. Conventional single-solution electrospinning, in which preformed cocrystals are added directly to the spinning solution, can also disrupt the hydrogen-bonded supramolecular structure of the cocrystal through solvent exposure, negating the very advantages cocrystallization was meant to provide.
To overcome that limitation, Darwesh and colleagues developed a hybrid electrospinning–electrospraying platform for the single-step fabrication of indomethacin–saccharin cocrystal-loaded mucoadhesive nanofibers for ocular delivery. Electrospinning uses a high-voltage electric field to draw a polymer solution into continuous nanofibers, forming a porous scaffold. Electrospraying, by contrast, produces fine charged droplets that solidify into particles, allowing cocrystals to be deposited onto the nanofiber matrix. In this system, electrospinning produces a continuous nanofibrous scaffold from a blend of poly(vinyl alcohol) (PVA) and poloxamer P407, polymers selected for biocompatibility, mucoadhesion, and tunable rheology, while electrospraying deposits the cocrystals directly onto that scaffold.
The key innovation, as the article describes it, lies in decoupling nanofiber formation from cocrystal generation. Rather than dissolving the drug and coformer together in the spinning solution, the cocrystals are formed in situ during electrospraying through supersaturation-driven nucleation as solvent evaporates from the charged droplets. This preserves the cocrystal lattice while enabling independent control over fiber morphology and particle size—capabilities the authors note are not achievable with conventional co-electrospinning, where everything shares one solvent environment.
The reported evaluation covered both single-layer and bilayer nanofiber architectures. According to the article, these experiments confirmed cocrystal formation, enhanced apparent solubility, and high drug incorporation efficiency. Particle sizes of roughly one micrometer were reported to fall within acceptable limits for ocular application, minimizing irritation risk. In vitro release studies demonstrated sustained drug delivery over 24 hours, with release kinetics that could be tuned through architectural optimization of the scaffold. Strong mucoadhesion was also observed, a property the article describes as critical for prolonging retention in the conjunctival sac and improving drug bioavailability. These are laboratory-stage findings: the article states that future work will focus on optimizing nanofiber architecture to further control release kinetics, improving formulation stability for scale-up, and conducting ex vivo and in vivo studies to evaluate ocular safety and pharmacokinetics before any clinical translation.
The article frames the hybrid platform as a significant advancement for ophthalmic therapy because it addresses the core weaknesses of conventional eye drops—poor solubility, rapid clearance, and the need for frequent dosing. By incorporating intact cocrystals into mucoadhesive nanofibers, the system points toward a single ocular insert capable of sustained drug release, which the authors suggest could offer a more effective and patient-compliant alternative to repeated instillation. The broader research program behind this work extends well beyond the eye. Darwesh’s group has reported personalized CT-based 3D-printed finger splints integrated with ibuprofen-loaded nanofibers for simultaneous mechanical support and localized therapy, bifiber floating oral scaffolds, nanofiber–hydrogel vaginal films for anti-HIV microbicide delivery, and hydrocortisone ocular minitablets optimized by design of experiments and produced via vacuum compression molding and fused deposition modeling. Patient-specific lung phantoms developed from CT imaging have also been used for radiological evaluation.
Her contributions have been recognized beyond the laboratory. Darwesh is a co-inventor on four USPTO-filed provisional patent applications, including the personalized CT scan-based 3D-printed finger splint with ibuprofen-loaded nanofibers, a smart nasal drug delivery device, a radiopharmaceutical delivery device, and a diagnostic imaging phantom platform, all advanced through the University of Mississippi Office of Technology Commercialization. Her work has earned two journal cover features in Molecular Pharmaceutics, in 2024 and 2026, invited membership in the Phi Kappa Phi and Rho Chi honor societies, and the University of Mississippi Graduate School Dissertation Fellowship for Fall 2026. Taken together, the spotlight presents a unifying theme: applying engineering principles—electrospinning, 3D printing, and hybrid fabrication—to build scalable, patient-centric drug delivery platforms across ocular, oral, nasal, vaginal, and radiopharmaceutical routes, with the cocrystal-loaded nanofiber scaffold serving as a flagship example of how crystal engineering and advanced manufacturing can be combined to tackle one of drug delivery’s oldest bottlenecks.
Subject of Research: Hybrid electrospinning–electrospraying fabrication of cocrystal-loaded mucoadhesive nanofibers for ocular drug delivery
Article Title: Spotlighting rising researcher Alaa Darwesh: engineering smart nanoscaffolds for ocular therapy: merging cocrystal science with electrospun nanofibers
Article References: Darwesh, A. Y. (2026). Spotlighting rising researcher Alaa Darwesh: engineering smart nanoscaffolds for ocular therapy: merging cocrystal science with electrospun nanofibers. AAPS Open, 12(1), Article 70. https://doi.org/10.1186/s41120-026-00208-9
Image Credits: AI Generated
DOI: 10.1186/s41120-026-00208-9
Keywords: ocular drug delivery, cocrystals, indomethacin, electrospinning, electrospraying, nanofibers, pharmaceutical engineering, solubility enhancement, mucoadhesion, sustained release, 3D printing, drug delivery systems
News Source: Denise Maddox. (October 27, 2026). Cocrystal-loaded nanofibers aim to keep eye drugs where they work. Scienmag.
