title: Hyaluronic Acid-Based Biocompatible Supramolecular Assembly for Sustained Release of Antiretroviral Drug.
abstract: Human immunodeficiency virus (HIV) infection and its associated diseases continue to increase despite the progress in our understanding of HIV biology and the availability of a number of antiretroviral drugs. Adherence is a significant factor in the success of HIV therapy and current HIV treatment regimens require a combination of antiviral drugs to be taken at least daily for the remainder of a patient's life. A drug delivery system that allows sustained drug delivery could reduce the medical burden and costs associated with medication nonadherence. Here, we describe a novel supramolecular assembly or matrix that contains an anionic polymer hyaluronic acid, cationic polymer poly-l-lysine, and anionic oligosaccharide sulfobutylether-beta-cyclodextrin. HIV reverse transcriptase inhibitors Zidovudine and Lamivudine were successfully encapsulated into the polymer assembly in a noncovalent manner. The physicochemical properties and antiviral activity of the polymer assemblies were studied. The results of this study suggest that the supramolecular assemblies loaded with HIV drugs exert potent antiviral activity and allow sustained drug release. A novel drug delivery formulation such as the one described here could facilitate our efforts to reduce the morbidity and mortality associated with HIV infections and could be utilized in the design of therapeutic approaches for other diseases.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California 95616. Electronic address: bwsong@ucdavis.edu.
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.affiliation: CycloLab, Budapest H-1097, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Puskás
authors.affiliation: CycloLab, Budapest H-1097, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Szente
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California 95616; Department of Internal Medicine, Meharry Medical College, Nashville, Tennessee 37208.
authors.forename: James E K
authors.initials: JEK
authors.lastname: Hildreth
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001672:Biocompatible Materials; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D019259:Lamivudine / Q000008:administration & dosage / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D015215:Zidovudine / Q000008:administration & dosage / Q000737:chemistry; D047392:beta-Cyclodextrins
chemical_list: D019380:Anti-HIV Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D047392:beta-Cyclodextrins; D011107:Polylysine; C093196:SBE4-beta-cyclodextrin; D019259:Lamivudine; D015215:Zidovudine; D006820:Hyaluronic Acid
keywords: HIV/AIDS; biodegradable polymers; controlled release; cyclodextrins; macromolecular drug delivery; polymeric drug delivery systems