Molecular pharmaceutics 2017 08 23() doi 10.1021/acs.molpharmaceut.7b00555
The purpose of this study is to engineer a model anti-HIV microbicide (Tenofovir) drug delivery system targeting HIV-1 envelope glycoprotein gp120 (HIV-1 g120) for the prevention of HIV sexual transmission. HIV-1 g120 and mannose responsive particles (MRP) were prepared through the layer-by-layer coating of calcium carbonate (CaCO3) with Concanavalin A (Con A) and glycogen. MRP average particle size ranged from 881.7±15.45 nm to 1130±15.72 nm, depending on the number of Con A layers. Tenofovir encapsulation efficiency in CaCO3 was 74.4% with drug loading of 16.3% (w/w). MRP was non-cytotoxic to Lactobacillus crispatus, VK2 and RAW 264.7 cells and did not induce any significant pro-inflammatory nitric oxide release. Overall, compared to control, no statistically significant increase in pro-inflammatory cytokines IL-1α, IL-1β, IL-6, MKC, IL-7 and TNFα levels was observed. Drug release profiles in the presence of methyl α-D-mannopyranoside and recombinant HIV-1 envelope glycoprotein gp120 followed Hixson-Crowell and Hopfenberg kinetic models, indicative of a surface-eroding system. The one Con A layer containing system was found to be the most sensitive (~2-fold increase in drug release vs. control SFS:VFS) at the lowest HIV gp120 concentration tested (25 µg/mL). Percent mucoadhesion, tested ex vivo on porcine vaginal tissue, ranged from 10% to 21% , depending on the number of Con A layers in the formulation. Collectively, these data suggest that the proposed HIV-1 g120 targeting, using MRP, potentially represent a safe and effective template for vaginal microbicide drug delivery, if future preclinical studies are conclusive.