title: A facile method for synthesizing water-soluble and superior sustained release anti-HIV prodrug SCs-d4T.
abstract: To efficiently deliver stavudine (d4T) for AIDS therapy, chitosan-stavudine conjugate (Cs-d4T) was synthesized. However, its poor water-solubility limited its clinical application. In this study, a sulphonated chitosan-stavudine conjugate (SCs-d4T) was synthesized with a mild SO3·Py complex sulphonation strategy. Chemical characteristics and morphology of Cs-d4T and SCs-d4T were performed by NMR, XRD, FTIR, ICP-AES and SEM. SCs-d4T demonstrated satisfactory solubility (106-bold of Cs-d4T solubility), good anti-HIV activity (6-fold of d4T anti-HIV activity), and well sustained release ability. The major release product O-isopropyl-5'-H-phosphonate of d4T (d4T-P-H) showed higher anti-HIV activity than d4T. For further evaluating the influence of linker and sulphonation strategy on anti-HIV activity, chitosan grafted with d4T by succinyl linker (Cs-sd4T) and SCs-d4T sulphonated by oleum were also prepared. The result showed that the O-isopropyl monophosphate linker of Cs-d4T and SO3·Py complex sulphonation strategy revealed higher anti-HIV activity than succinyl linker of Cs-sd4T and oleum sulphonation strategy, respectively.
authors: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors: Ling
authors: L
authors: Li
authors: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors: Jin
authors: J
authors: Zhang
authors: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors: Chao
authors: C
authors: Li
authors: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors: Liqiang
authors: L
authors: Chen
authors: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, PR China. Electronic address: qiao_group@163.com.
authors: Renzhong
authors: R
authors: Qiao
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D011355:Prodrugs / Q000008:administration & dosage*; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D011355:Prodrugs; D014867:Water
keywords: Chitosan; Stavudine; Sulphonation; Sustained release; Water solubility