Translational evaluation of electrospun drug delivery systems: fabrication, pharmacokinetics, and tissue-specific host responses

Abstract

Pre-exposure prophylaxis (PrEP) is an oral regimen of antiretroviral (ARV) drugs for the prevention of HIV. However, near-perfect adherence to PrEP is needed to maintain protective drug concentrations in the lower female reproductive tract (FRT). To address issues of adherence to medications like PrEP, we investigate the use of drug-loaded electrospun materials as a long-acting drug delivery vehicle. Electrospinning has previously demonstrated the ability to formulate physiochemically diverse ARV drugs into stable solid dispersions. Here, we investigate various formulations of drug-loaded electrospun materials and further demonstrate the scalable potential of electrospinning. Electrospinning is used to formulate long-acting triple-drug releasing material as an adherence-independent subcutaneous implant, and we assess the pharmacokinetics and biocompatibility of these implants in mice. Finally, towards the development of adherence-independent and topical electrospun devices, we probe local tissue hosts responses in the FRT in baboons. Research from this thesis provides new insight into drug release kinetics and material biocompatibility resulting from drug delivery systems specifically within subcutaneous and FRT tissue environments.