Layer-by-Layer Engineered Microbicide Drug Delivery System Targeting HIV-1 gp120: Physicochemical and Biological Properties.

The purpose of this study was 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 (CaCO) 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 CaCO was 74.4% with drug loading of 16.3% (w/w). MRP was non-cytotoxic to Lactobacillus crispatus, human vaginal keratinocytes (VK2), and murine macrophage RAW 264.7 cells and did not induce any significant proinflammatory nitric oxide release. Overall, compared to control, no statistically significant increase in proinflammatory cytokine IL-1α, IL-1β, IL-6, MKC, IL-7, and interferon-γ-inducible protein 10 (IP10) 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 suggested 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.