Pre-exposure prophylactic mucoadhesive sodium alginate microsphere laden pessaries for intravaginal delivery of tenofovir disoproxil fumarate

Abstract

The research aimed to develop novel bioadhesive sodium alginate (Na-Alg) microspheres laden pessaries for intravaginal delivery of tenofovir disoproxil fumarate (TDF), to overcome limitations of conventional dosage forms. Twelve batches of microspheres formulated by emulsification gelation method indicated that drug-polymer ratios and polymer type affected particle size, drug release, and entrapment efficiency (%EE). Microspheres of batch EH-8 with drug: polymer ratio of 1:4 containing equal amounts of Na-Alg and HPMC K100M displayed optimal %EE (62.09 ± 1.34 %) and controlled drug release (97.02 ± 4.54 % in 12 h). Particle size analysis in Matersizer indicated that microspheres (EH-8) displayed a surface-mean diameter of 11.06 ± 0.18 μm. Ex-vivo mucoadhesion studies on rabbit mucosa indicated that microspheres (EH-8) adhered well for 12 h. Microspheres integrated into pessaries displayed a sustained release profile (95.31 ± 1.37 % in 12 h) in simulated vaginal fluid. In vivo studies in rabbits indicated that pessaries displayed a significantly higher Cmax (41.18 ± 3.57 ng/mL) (P < 0.005) and reduced Tmax (1.00 ± 0.01 h) (P < 0.0001) of TDF concentrations in vaginal fluid compared to oral tablets. The microparticulate pessaries with the ability to elicit higher vaginal fluid levels in the crucial initial hours of insertion demonstrates a potential novel platform to offer better self-protection to HIV-negative women against HIV during sexual intercourse.