Development of a melt-cast microneedle patch for sustained drug release of islatravir

Abstract

Low adherence to daily oral drug regimens is a significant obstacle in effectively managing chronic therapies like HIV treatment, pre-exposure prophylaxis (PrEP), and contraception. While long-acting injectables eliminate the need for daily compliance, they often require administration by healthcare professionals. To facilitate self-administration of long-acting treatments, we developed a microneedle patch (MNP) for the sustained release of islatravir or levonorgestrel, used for HIV treatment/PrEP or contraception, respectively. The MNPs were produced using a melt-casting technique to quickly create biodegradable polycaprolactone microneedles for continuous drug delivery. The low melting point of polycaprolactone and the high thermal stability of islatravir and levonorgestrel allowed melt casting at 65 °C. Incorporating centrifugation during fabrication improved the attachment of microneedles to the patch backing, making it easier to remove MNPs from the mold and ensuring effective microneedle insertion into skin. The MNPs demonstrated a sustained release of islatravir with roughly first-order release kinetics for ∼40 days in vitro. We conclude that MNPs made with a simple melt-casting process can enable prolonged drug release for HIV treatment/PrEP, contraception, and other therapeutic applications.