Evaluation of poly(lactic-co-glycolic acid) and poly( dl -lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection

Abstract

More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections.

Multipurpose tenofovir disoproxil fumarate electrospun fibers for the prevention of HIV-1 and HSV-2 infections in vitro

“…Despite both HFIP and TFE sharing many characteristics such as high polarity and similar molecular structure, there are several key differences that may impact fiber properties. As previously described [35], TFE has a higher dielectric constant (26.1 F/m) compared to HFIP (16.7 F/m) [57]. This increased charge capacity may confer additional instability to TFE solvents during electrospinning, requiring more polymer to produce well-defined fiber morphology [58].…”

“…For blank EFs, 15–20% PLGA w/w and 12–20% PLCL w/w were dissolved in either 3 mL TFE or HFIP solvent overnight while shaking at 37°C. The following day, 2 mL of PLGA or PLCL solution was aspirated into, and electrospun from, a 3 mL plastic syringe as previously described [26, 35]. All formulations were electrospun with a flow rate of 2.0 mL/hr and an applied voltage of 20 kV.…”

“…In another study, ACV was incorporated into EFs. Release eluate collected up to 28 days post-release provided sustained protection against HSV-2 infection in vitro [35]. Other work that demonstrated protection against both HSV-2 and HIV-1 in vitro and in vivo , examined the incorporation of TDF, a newer and more potent prodrug of TFV, into IVRs.…”

Surface-Modified Melphalan Nanoparticles for Intravitreal Chemotherapy of Retinoblastoma

“…Avidin palmitate was synthesized for conjugation to NPs as previously described. 15,16,18,19 Briefly, 40 mg avidin (A9275, Sigma-Aldrich Corp., St. Louis, MO, USA) was dissolved in 4.8 mL 2% sodium deoxycholate (NaDC) in phosphate-buffered saline (PBS) warmed to 378C. Palmitic acid-NHS (PA-NHS, Sigma-Aldrich Corp.) was dissolved in 2% NaDC to a final concentration of 1 mg/mL and sonicated until well-mixed.…”

Application of electrospun fibers for female reproductive health

“…These formulations achieved both burst- and sustained-release of all three compounds in vitro , and MVC and AZT eluted from the fibers were found to maintain antiviral activity against HIV-1 BaL, while activity of eluted acyclovir was not tested. However, Aniagyei et al have shown release of ACV from poly (lactic-co-glycolic) acid (PLGA) and poly(lactide-co-caprolactone) (PLCL) over the course of 28 days, and observed complete viral inhibition with eluted doses of 1–200 μg/mL [47]. Carson et al showed programmable release of tenofovir (TFV), AZT, MVC and raltegravir (RAL) from fibers composed of blends of poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone (PCL) [48].…”