¹Department of Pharmaceutics, Research scholar, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Andhra Pradesh, 522022. India
²Department of Pharmaceutics, Associate Professor, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Andhra Pradesh, 522022. India DOI : 10.29228/jrp.814 Tenofovir is an antiviral drug indicated for the treatment of infections caused by the human immunodeficiency virus (HIV) and hepatitis B virus (HBV). TNF is classified as a BCS Class III drug, indicating its ability to readily dissolve in gastrointestinal fluids with poor permeability across intestinal membranes results in a lower absorption rate, ultimately restricting its bioavailability. The primary challenges associated to enhancing the bioavailability of TNF involve intestinal degradation and efflux transport facilitated by Multidrug resistance protein1. TNF-loaded proniosomes were formulated using 32 factorial design by applying slurry method of preparation with a molar ratio of 2.5:1:1.5 for cholesterol, span 60, and maltodextrin, respectively. Maltodextrin-based polymeric nanoparticles exhibited desirable nano-scale properties, including size, polydispersity index , and zeta potentials, which fell within acceptable ranges. The successful PNFs (T-PN3, T-PN4, and T-PN7) demonstrated TNF entrapment in the range of 92.96 to 96.28%. The hydration volume and hydration time of proniosome-based niosomes for delivering TNF were optimized and the results demonstrated the structural homogeneity of niosomes derived from proniosomes. Transmission electron microscopy (TEM) analysis indicated that the niosomes exhibit a uniform and smooth surface morphology. Successful formulations were further characterized for their powder behaviour by angle of repose, TNF interactions with formulation components by FT-IR and DSC thermal analysis. The T-PN3 and T-PN7 formulations demonstrated a high in-vitro release rate of approximately 99% in PBS. Additionally, the cellular uptake of TNF from successful PNFs in NCI-N87 cells ranged from 81% to 83%, indicating that T-PN3 and T-PN7 exhibited superior performance compared to free TNF and the commercially available tenofovir. Further mechanistic analysis was conducted using MDR1 efflux studies and western blot techniques. The results demonstrated that both T-PN3 and TPN7 effectively inhibited the efflux transport of TNF through MDR1 in MDCK-MDR1 and Caco-2 cells. Keywords : Tenofovir; Proniosomes; Niosomes; MDR-mediated drug efflux; Slurry technique