Emerging trends in polymeric mucoadhesive nanocarriers: a promising option for intravaginal HIV preexposure prophylaxis.

The emergence of novel long-acting and antiretroviral (ARV) drug delivery systems has reshaped the landscape of HIV pre-exposure prophylaxis (PrEP). Intravaginal delivery platforms are increasingly recognised for their ability to deliver ARVs directly at the portal of viral entry. These systems are well retained at the portal, ensuring sustained local inhibitory levels, minimising systemic exposure. Compared to oral PrEP, these systems offer better protection against viral transmission, reduce dosing frequency and minimise systemic side effects. Among these systems, polymeric nanoparticles (NPs) stand out due to their customisable surface chemistry, mucoadhesive potential and sustained drug release profiles, ensuring enhanced mucosal retention and minimal systemic absorption. Recent innovations integrate these NPs into versatile platforms such as in situ gelling systems, bioadhesive films, microneedles, vaginal rings and electrospun nanofibres. These specialised platforms have demonstrated superior user acceptance, stability and pharmacokinetics compared to traditional vaginal formulations. Cell-based HIV challenge models using engineered TZM-bl and PHA-stimulated peripheral blood mononuclear cells (PBMCs) have emerged as reliable in silico tools for evaluation of viral inhibition, cytotoxicity and mucosal interaction of NPs. This review critically highlights recent advances in intravaginal polymeric NP-based carrier systems for effective and sustained HIV prevention.