Innovative Multilayered Electrospun Fiber Systems for Dual‐Action HIV Prophylaxis and Nonhormonal Contraception

<b>Background:</b> Electrospun fiber drug delivery systems, integrated into multipurpose prevention technologies, offer a promising solution for women facing health risks from HIV/STIs and unmet contraceptive needs by providing on-demand protection in a single dosage form. This study investigates the potential of a multilayer electrospun fiber construct for pH-responsive and sustained release of the HIV microbicide tenofovir (TFV) and the CatSper channel blocker nifedipine (NFP) respectively. <b>Method:</b> Electrospun fibers were fabricated in a stacked architecture by blend electrospinning using polycaprolactone (PCL) as the backing layer for delivering NFP and cellulose acetate phthalate (CAP) as the top layer for delivering TFV. An analysis of surface morphology, mechanical and chemical properties, mucoadhesion, drug release profiles, encapsulation efficiency, and safety assessments was performed. <b>Results:</b> An encapsulation efficiency of 52.13% was achieved for TFV, with a drug loading of 7.00%, while for NFP, the encapsulation efficiency was 63.86%, with a drug loading of 0.56%. The top layer exhibited a pH-responsive release profile and Fickian diffusion in both SVF and SVF/SF environments, while the backing layer showed Fickian diffusion in SVF and a release profile closer to zero-order in SVF/SF. <b>Conclusion:</b> This study highlights the potential of multilayered CAP/PCL electrospun fibers for intravaginal delivery of TFV and NFP, aimed at the pre-exposure prophylaxis of HIV-1 and prevention of unplanned pregnancy.