Coaxially electrospun fiber-based microbicides facilitate broadly tunable release of maraviroc

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.

Application of electrospun fibers for female reproductive health

“…Electrospinning is a proven way to achieve high drug loading of therapeutics into a solid dosage form. Furthermore, it is possible to control the architecture at both the fiber- and macroscopic-levels such as fabricating core-sheath morphologies [26], multilayered composites of drugs and polymers [27, 28], and various three-dimensional geometries [29]. Finally, the scale-up production of electrospun fibers has been accelerated by developments made in industries such as filtration technologies, and there are commercially available instruments that produce fibers at rates up to three orders of magnitude higher than laboratory-scale electrospinning rigs [30].…”

“…Non-commercially available PLGA-based polyurethane polymers have also been electrospun with TFV for sustained release in vitro [50]. MVC has been formulated into both coaxial electrospun fibers with an ethylcellulose core and polyvinylpyrrolidone (PVP) shell [26], as well as amorphous solid dispersions in PVP and PEO [51]. Grooms et al investigated the effect of incorporating griffithsin (GRFT), a protein that has been shown to have potent activity against both HIV-1 and HSV-2, by grafting the biologic onto the surface of electrospun fibers, as opposed to encapsulating GRFT within the fiber [52].…”

A Review of Injectable and Implantable Biomaterials for Treatment and Repair of Soft Tissues in Wound Healing

“…All fiber formulations promoted L292 fibroblasts proliferation ( Figure 5(c)), suggesting a good biomaterials to enhance wound healing. With respect to functional ability, not only do electrospun nanofibers have the ability to carry small molecule drugs [79,80], biological active components 8 Journal of Nanotechnology (e.g., growth factors [81], proteins and enzymes [82], and genes [83]), and even cells, but also their surface can be functionalized with signaling molecules to promote cell activities [84]. This makes electrospun nanofibers a multifunctional drug delivery system.…”

Nanoparticle-releasing nanofiber composites for enhanced in vivo vaginal retention

“…Electrospun nanofibers have recently been investigated as a platform for vaginal drug delivery [10–18]. Nanofibers (NF) are a solid-state dosage form, which may overcome challenges with user adherence by reducing messiness and leakage that has been associated with liquid or gel-based dosage forms.…”