title: Synthesis of lamivudine stearate and antiviral activity of stearic acid-g-chitosan oligosaccharide polymeric micelles delivery system.
abstract: To increase lipophilicity of water-soluble antiviral drug, the prodrug of Lamivudine (LA), Lamivudine stearate (LAS) was synthesized via ester linkage between LA and stearic acid. After the esterification, the octanol-water partition coefficient (logP) of LA increased from -0.95 to 1.82. Stearic acid-g-chitosan oligosaccharide (CSO-SA) micelles have demonstrated fast internalization and accumulation ability to tumor cells. Herein, the CSO-SA with 3.79% amino substitution degree (SD) was prepared for loading LAS. The critical micelle concentration (CMC) of CSO-SA was about 0.032mg/ml. The micelles with 1mg/ml CSO-SA concentration had 460.8nm average diameters with a narrow size distribution and 29.7mV surface zeta potential. After LAS was incorporated, the micellar size decreased and the zeta potential increased. The LAS loaded CSO-SA micelles (CSO-SA/LAS) possessed high entrapment efficiency and drug loading. LA release from CSO-SA/LAS showed a pH-dependent behavior. The release rate of LA from CSO-SA/LAS increased significantly as the pH of release medium reduced from 7.4 to 6.2. CSO-SA/LAS presented a low cytotoxicity and high cellular uptake percentage of LAS against HBV transfected tumor cells (HepG2.2.15). In vitro anti-HBV activities of CSO-SA/LAS presented more conspicuous inhibitory effects on antigen expression and DNA replication compared with LA and LAS.
authors: College of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Qian
authors: Q
authors: Li
authors: Yong-Zhong
authors: YZ
authors: Du
authors: Hong
authors: H
authors: Yuan
authors: Xing-Guo
authors: XG
authors: Zhang
authors: Jing
authors: J
authors: Miao
authors: Fu-De
authors: FD
authors: Cui
authors: Fu-Qiang
authors: FQ
authors: Hu
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D006515:Hepatitis B virus / Q000187:drug effects; D019259:Lamivudine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008823:Micelles; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry*; D013229:Stearic Acids / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D008823:Micelles; D009844:Oligosaccharides; D013229:Stearic Acids; D019259:Lamivudine; D048271:Chitosan