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

Abstract

Sexually transmitted infections affect hundreds of millions of people worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir disoproxil fumarate (TDF), exhibited sustained-release for up to 4 weeks, and provided complete in vitro protection against HSV-2 and HIV-1 for 24 hr and 1 wk, respectively, based on the doses tested. In vitro cell culture and EpiVaginal tissue tests confirmed the safety of fibers in vaginal and cervical cells, highlighting the potential of PLGA and PLCL EFs as multipurpose next-generation drug delivery vehicles.

Relating Advanced Electrospun Fiber Architectures to the Temporal Release of Active Agents to Meet the Needs of Next-Generation Intravaginal Delivery Applications

“…For example, the antiretroviral TFV and its pro-drug TDF have similar structures and both work as nucleoside reverse transcriptase inhibitors yet possess markedly different hydrophobicities. As such, a delivery platform designed to prolong TFV release may result in different release kinetics of TDF, requiring the formulation of distinct delivery vehicles specific to the selected active agents [56,116,118,175,176]. Furthermore, each active agent may necessitate specific temporal dosing regimens to provide protection or treatment.…”

“…The enhanced tunability and versatility provided by the core and shell layers of coaxial fibers make them excellent candidates for intravaginal delivery applications. While uniaxial fibers have been studied for sustained- and stimuli-responsive release of active agents in the FRT [6,114,115,116,117,118,119], they have faced challenges in providing the sustained-release of therapeutically relevant concentrations of individual active agents and effectively modulating the release of multiple agents core [6]. Often, compatibility between the polymer and encapsulant can pose challenges to achieving sustained-release with uniaxial fibers, while coaxial fibers may circumvent this issue by integrating two different polymers, enabling the separation of agents within a compatible polymer formulation (core or shell).…”

Rapid Release Polymeric Fibers for Inhibition of Porphyromonas gingivalis Adherence to Streptococcus gordonii

“…The fiber was placed in a labeled petri dish and kept in a desiccator for 24 h before characterization. The desiccated fibers were stored in 4 • C until use (Tyo et al, 2017).…”

“…The in vitro release of F-BAR from fibers was measured by gentle agitation of EFs in phosphate buffered saline (PBS, pH 7.4) at 37 • C. At fixed time points (1, 2, 4, 8, 12, and 24 h), samples were collected and the amount of F-BAR released from the EFs was quantified via fluorescence spectroscopy, against an F-BAR standard in PBS (Kalia et al, 2017;Tyo et al, 2017;Mahmoud et al, 2018).…”

“…The absorbance of each well was read at 570 nm, and the sample absorbance was normalized to the absorbance of medium-only treated cells. Cells were treated with 10% DMSO media (100 µL DMSO in 900 µL media) as a positive control for cell death (Tyo et al, 2017;Mahmoud et al, 2019).…”