Electrospun Tenofovir/Emtricitabine-Zein Nanofibers for Pre-Exposure Prophylaxis Platform against HIV through Vaginal Delivery

Human immunodeficiency virus (HIV) remains a major global public health concern, particularly affecting vulnerable populations. Pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is a strategy recommended by the World Health Organization to prevent sexual transmission of HIV. Vaginal delivery systems based on nanofibers offer several advantages, including high surface area, mucoadhesiveness, and controlled drug release. This study aimed to develop and characterize TDF and FTC-loaded zein-based electrospun nanofibers for vaginal PrEP. Electrospun hybrid nanofibers were produced using zein in combination with mucoadhesive polymers such as polyvinylpyrrolidone (PVP) and poly-(ethylene oxide) (PEO). The nanofibers were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Mechanical strength and mucoadhesive properties were evaluated for vaginal use. In vitro release of TDF and FTC from the nanofibers was also investigated. The ZK7-TF formulation showed 898.048 ± 300.838 nm uniform diameters and porosity 60.03%. Mucoadhesion work reached 0.121 ± 0.014 mJ·cm^-2, while mechanical integrity was supported by 1.510 ± 0.501 MPa tensile strength and 2.617 ± 0.977% elongation at break values. Hydrophilic properties of TDF and FTC-loaded formulations were evidenced by contact angles of <90°. The release studies showed controlled release of TDF and FTC for 24 h. Zein-based hybrid nanofibers incorporating mucoadhesive polymers represent a promising drug delivery system for the vaginal delivery of antiretroviral drugs as an effective and patient-compliant strategy for HIV prevention. This study provides a comprehensive formulation approach, combining zein with poly-(ethylene oxide) and polyvinylpyrrolidone to fine-tune nanofiber morphology, mechanical strength, mucoadhesion, and drug release properties for vaginal delivery.