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

Abstract

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.

Mannose-decorated hybrid nanoparticles for enhanced macrophage targeting

“…Mannosylated compounds, macromolecules, and nanoparticles often undergo specific interaction with mannose receptors (CD206) on cells, which involves receptor-mediated endocytosis and internalization into cytoplasmic compartments. Such biological processes have been reported in the case of various nanoparticles targeted delivery to macrophages [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] . To confirm such specific interactions between MDNPs and U937 cells, we performed a series of uptake assays by varying mannose density on F127-TA nanoparticles and their time-dependent interaction with cells ( Fig.…”

“…Nanoparticles provide distinct advantages for therapeutic application over traditional delivery methods by improving the targeted efficacy, pharmacokinetics, and bioavailability of the drugs being delivered. Functionalization of an active targeting motif creates opportunity and allows superior targeting of monocytes and macrophages with a high specificity and affinity [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] . Major criteria for construction of such active targeted nanosystems are high ligand density and a favorable orientation for the ligand.…”

“…Self-assembled units decorated with mannosides produces multifunctional supramolecular nanoparticles with remarkably higher entry, minimal cytotoxicity, and almost negligible cytokine production in macrophages. Nanosystems based on gold, quantum dot, gelatin, poly(lysine), and poly(propylene imine) were proven to be promising platforms for targeting macrophages [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] . Similarly, polymer nanosystems found to be a unique nanoparticle formulation that can be applied for wide variety medical applications.…”

Current State of Microbicide Development

“…The study revealed that after 30 minutes of exposure, the concentration released (10 μg/mL) is equivalent to the published IC 90 for the drug. Recently, a research article published by Coulibaly et al 55 utilized HIV-1 gp120 fragment's ability to interact with the drug carrier to trigger drug release. In this study, tenofovir was encapsulated in a mannose responsive particle using calcium carbonate, concanavalin A, and glycogen.…”

Electrical Immunosensor Made with Antigenic Peptide NS5A‑1 Immobilized onto Silk Fibroin for Diagnosing Hepatitis C

“…27,28 The assembly of the LbL film is based on intermolecular interactions between the materials, so a great interest is dedicated to find suitable materials for alternating with the biomolecule which can retain its specific biological function. [27][28][29][30][31][32] An alternative approach to increase sensitivity is the use of electrical impedance measurements, which are normally employed to exploit changes in dielectric properties, charge distribution and/or thickness of the dielectric layer when an antibody-antigen complex is formed on the electrode surface. [33][34][35] In this paper, we report on electrical impedance measurements for detecting the anti-HCV antibody, again exploiting the biorecognition between the antibody and the antigenic peptide NS5A-1 immobilized in LbL films with SF.…”