Tenofovir alafenamide fumarate loaded long-acting microsphere for HIV pre-exposure prophylaxis

The Human Immunodeficiency Virus (HIV) continues to be a major global health issue, with 38.4 million people infected at the end of 2021. The daily dosage regimen of Anti-retroviral (ARV) treatment leads to poor treatment adherence and patients' non-compliance. Tenofovir and its prodrugs, such as Tenofovir alafenamide (TAF) are generally used for the Pre-Exposure Prophylaxis (PrEP) of HIV. The current work focusses on the development of long-acting TAF loaded Poly-Lactic-co-Glycolic Acid (PLGA) Microspheres (MS) to improve the treatment adherence and patient compliance. MS were formulated using the industrially scalable in-line homogenizer approach using the solid-in-oil-in-water (S/O/W) emulsion solvent evaporation method. The surface morphology study carried out by SEM indicated the formation of dense, non-porous and spherical MS. The Differential Scanning Calorimetry (DSC) and X-ray Diffractometry (XRD) study revealed the formation of an amorphous form of TAF in the MS. The in vitro release study indicated the lower initial burst release of TAF and sustained release of TAF up to 15 days from the MS. The cytotoxicity and HIV inhibitory studies in the reporter TZM-bl cell line with different HIV-1 strains indicated the safety and effectiveness of TAF loaded PLGA MS. Thus, the long-acting MS would be a better alternative as a PrEP measure for HIV infection.