Drug-Eluting Fibers for HIV-1 Inhibition and Contraception

Abstract

Multipurpose prevention technologies (MPTs) that simultaneously prevent sexually transmitted infections (STIs) and unintended pregnancy are a global health priority. Combining chemical and physical barriers offers the greatest potential to design effective MPTs, but integrating both functional modalities into a single device has been challenging. Here we show that drug-eluting fiber meshes designed for topical drug delivery can function as a combination chemical and physical barrier MPT. Using FDA-approved polymers, we fabricated nanofiber meshes with tunable fiber size and controlled degradation kinetics that facilitate simultaneous release of multiple agents against HIV-1, HSV-2, and sperm. We observed that drug-loaded meshes inhibited HIV-1 infection in vitro and physically obstructed sperm penetration. Furthermore, we report on a previously unknown activity of glycerol monolaurate (GML) to potently inhibit sperm motility and viability. The application of drug-eluting nanofibers for HIV-1 prevention and sperm inhibition may serve as an innovative platform technology for drug delivery to the lower female reproductive tract.

Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV

“…Spiked samples were prepared by adding maraviroc from 1 mg/ml stock solution to dissolved blank fibers with and without Tween 20. The maraviroc standard, spiked samples, and unknown samples were detected by UV-HPLC as described previously (8,23). The calibration curve was prepared in Prism (GraphPad) using 1/C 2 weighting to minimize residuals.…”

“…The in vitro cytotoxicity of the surfactants Tween 20 (Fisher), Tween 80 (Fisher), glycerol monolaurate (Sigma-Aldrich), and nonoxynol-9 (Options Conceptrol) were evaluated using a cell titer blue assay (Promega) according to the manufacturer's instructions. The in vitro activity of maraviroc in fiber eluates (from sink release assays) was evaluated using a cell-based reporter assay described previously (8,25). Briefly, TZM-bl cells and an HIV-1 BaL isolate were obtained from the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH (http://www.aidsreagent.org/).…”

“…Moreover, microbicide films reported in literature have low drug loadings (less than 1.5 wt%) (6,7), which when coupled with their small dosage size limits their application to only highly potent antiretroviral (ARV) drugs. Recently, Ball et al and Huang et al demonstrated that electrospun fibers could release a range of active ARV drugs and spermicides (8) and that such release could occur in response to stimuli, such as a semen-induced rise in pH (9). Furthermore, Huang et al demonstrated high loading (15 wt%) of tenofovir disoproxil into electrospun fibers (9), which would reduce the required dosage size.…”

“…These rapidly dissolving fibers could be ideally suited for use as a pericoital delivery system, since they have a very high surface areato-volume ratio, can be made of the same polymers as films and tablets, and, unlike other nanosystems, like nanoparticles, are easily handled. Electrospun fibers are smooth (materials appear textured on a micrometer scale), fabric-like materials (capable of repeated folding without breakage and postproduction shaping) that could be inserted vaginally either with a finger or with an applicator (8).…”

Delivery of multipurpose prevention drug combinations from electrospun nanofibers using composite microarchitectures

“…Huang et al 13 and Ball et al 14 have used electrospun fabrics with variety of antiretroviral drugs but never in combination. Combination drug delivery from electrospun fabrics can be achieved by the co-delivery of multiple drugs encapsulated within the same fiber or into separate fibers.…”