Zinc-Stabilized Chitosan-Chondroitin Sulfate Nanocomplexes for HIV-1 Infection Inhibition Application

Abstract

Polyelectrolyte complexes (PECs) constituted of chitosan and chondroitin sulfate (ChonS) were formed by the one-shot addition of default amounts of polyanion to an excess of polycation. Key variables of the formulation process (e.g., degree of depolymerization, charge mixing ratio, the concentration, and pH of polyelectrolyte solutions) were optimized based on the PECs sizes and polydispersities. The PECs maintained their colloidal stability at physiological salt concentration and pH thanks to the complexation of polyelectrolytes with zinc(II) ion during the nanoPECs formation process. The PECs were capable of encapsulating an antiretroviral drug tenofovir (TF) with a minimal alteration on the colloidal stability of the dispersion. Moreover, the particle interfaces could efficiently be functionalized with anti-OVA or anti-α4β7 antibodies with conservation of the antibody biorecognition properties over 1 week of storage in PBS at 4 °C. In vitro cytotoxicity studies showed that zinc(II) stabilized chitosan-ChonS nanoPECs were noncytotoxic to human peripheral blood mononuclear cells (PBMCs), and in vitro antiviral activity test demonstrated that nanoparticles formulations led to a dose-dependent reduction of HIV-1 infection. Using nanoparticles as a drug carrier system decreases the IC50 (50% inhibitory concentration) from an aqueous TF of 4.35 μmol·L(-1) to 1.95 μmol·L(-1). Significantly, zinc ions in this system also exhibited a synergistic effect in the antiviral potency. These data suggest that chitosan-ChonS nanoPECs can be promising drug delivery system to improve the antiviral potency of drugs to the viral reservoirs for the treatment of HIV infection.

Novel Polymeric Formulation for Removal of Gastrointestinal Polyps by Digestive Endoscopy

“…Equally, Zn is related to the gene expression of inflammatory cytokines also involved in intestinal wound healing and epithelial repair [21]. Zn also promotes the stabilization of chains of HA [22,23]. Finally, the inclusion of methylene blue as a staining dye was aimed at identifying the lateral and deep margins of the target lesion.…”

Fundamental and Practical Aspects in the Formulation of Colloidal Polyelectrolyte Complexes of Chitosan and siRNA

“…[95] Following this approach, zinc-stabilized complexes of chitosan/hyaluronan or chitosan/chondroitin sulfate have been developped for the HIV-1 inhibition. [96] Similarly, complexes of chitosan-ATP (adenosine triphosphate) or chitosan-TPP (tripolyphosphate) can be stabilized in physiological media with Fe 3+ ions that bind strongly to amine groups of chitosan and phosphate groups of ATP. [97] 4.…”

Review of Zinc(II) Scaffolds: Efficient Role in Gene Delivery

“…Recently, Thierry Delair et al has reported, how the Zinc-stabilized chitosanchondroitin sulfate (ChonS) based nano-complexes ( Figure 8) can be applied for inhibiting the HIV-1 infection. During the cell-culture examination, they found that Zn(II)-stabilized chitosan-ChonS nanoPECs [42] were non-cytotoxic to human peripheral blood mononuclear cells and dose-dependent reduction of HIV-1 infection. By using the above nano-complex as a drug vector, they achieved a high transfection efficacy and reduced the 50% inhibitory concentration (IC 50 ) of aqueous tenofovir (TF) to 1.95 μmolL À 1 from 4.35 μmolL À 1 .…”