title: 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.
authors.affiliation: Ingénierie des Matériaux Polymères, UMR CNRS 5223, Université Claude Bernard Lyon 1 , 15 Bd. André Latarjet, 69622 Villeurbanne Cedex, France.
authors.forename: Danjun
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institut de Biologie et Chimie des Protéines UMR 5305, CNRS/Université de Lyon , 69367 Lyon Cedex 07, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Ensinas
authors.affiliation: Institut de Biologie et Chimie des Protéines UMR 5305, CNRS/Université de Lyon , 69367 Lyon Cedex 07, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.affiliation: ADJUVATIS-7 , passage du Vercors, 69367 Lyon Cedex 07, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Primard
authors.affiliation: B-Cell Design , 98 Rue Charles Legendre, 87000 Limoges, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Cuvillier
authors.affiliation: B-Cell Design , 98 Rue Charles Legendre, 87000 Limoges, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Champier
authors.affiliation: Groupe Immunité des Muqueuses et Agents Pathogènes, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, Université de Lyon , 15 rue Ambroise Paré, 42023 Saint-Etienne Cedex 2, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Paul
authors.affiliation: Ingénierie des Matériaux Polymères, UMR CNRS 5223, Université Claude Bernard Lyon 1 , 15 Bd. André Latarjet, 69622 Villeurbanne Cedex, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Delair
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D048271:Chitosan / Q000737:chemistry*; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003102:Colloids / Q000737:chemistry; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D011108:Polymers / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D003102:Colloids; D011108:Polymers; D002809:Chondroitin Sulfates; D048271:Chitosan; D015032:Zinc
keywords: HIV infection inhibition; chitosan; chondroitin sulfate; polyelectrolyte complexes; stabilization