Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically < 1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning.

Electrospun nanofibers have the potential to achieve high drug loading and the ability to sustain drug release. Mechanical properties of the drug-incorporated fibers suggest the importance of drug-polymer interactions. In this study, we investigated the mechanical properties of electrospun polycaprolactone (PCL) and poly (D,L-lactic-co-glycolic) acid (PLGA) fibers at various blend ratios in the presence and absence of a small molecule hydrophilic drug, tenofovir (TFV). Young׳s modulus of the blend fibers showed dependence on PLGA content and the addition of the drug. At a PCL/PLGA (20/80) composition, Young׳s modulus and tensile strength were independent of drug loading up to 40wt% due to offsetting effects from drug-polymer interactions. In vitro drug release studies suggested that release of TFV significantly decreased fiber mechanical properties. In addition, mechanically stretched fibers displayed a faster release rate as compared to the non-stretched fibers. Finally, drug partition in the blend fibers was estimated using a mechanical model and then experimentally confirmed with a composite of individually stacked fiber meshes. This work provides scientific understanding on the dependence of drug release and drug loading on the mechanical properties of drug-eluting fibers.

Wound healing is a complex tissue regeneration process that promotes the growth of new tissue to provide the body with the necessary barrier from the outside environment. In the class of non-healing wounds, diabetic wounds, and ulcers, dressing materials that are available clinically (e.g., gels and creams) have demonstrated only a slow improvement with current available technologies. Among all available current technologies, electrospun fibers exhibit several characteristics that may provide novel replacement dressing materials for the above-mentioned wounds. Therefore, in this review, we focus on recent achievements in electrospun drug-eluting fibers for wound healing applications. In particular, we review drug release, including small molecule drugs, proteins and peptides, and gene vectors from electrospun fibers with respect to wound healing. Furthermore, we provide an overview on multifunctional dressing materials based on electrospun fibers, including those that are capable of achieving wound debridement and wound healing simultaneously as well as multi-drugs loading/types suitable for various stages of the healing process. Our review provides important and sufficient information to inform the field in development of fiber-based dressing materials for clinical treatment of non-healing wounds.

No abstract

Electrospun fibers show potential as a topical delivery system for vaginal microbicides. Previous reports have demonstrated delivery of anti-HIV and anti-STI (sexually transmitted infection) agents from fibers formulated using hydrophilic, hydrophobic, or pH-responsive polymers that result in rapid, prolonged, or stimuli-responsive release, respectively. However, coaxial electrospun fibers have yet to be evaluated as a highly tunable microbicide delivery vehicle. In this research, we explored the opportunities and limitations of a model coaxial electrospun fiber system to provide broad and tunable release rates for the HIV entry inhibitor maraviroc. Specifically, we prepared ethyl cellulose (EC)-shell and polyvinylpyrrolidone (PVP)-core fibers that were capable of releasing actives over a range of hours to several days. We further demonstrated simple and effective methods for combining core-shell fibers with rapid-release formulations to provide combined instantaneous and sustained maraviroc release. In addition, we investigated the effect of varying release media on maraviroc release from core-shell fibers, and found that release was strongly influenced by media surface tension and drug ionization. Finally, in vitro cell culture studies show that our fiber formulations were not cytotoxic and that electrospun maraviroc maintained similar antiviral activity compared to neat maraviroc.