In vitro/in vivo studies of a novel anti-HIV self-assembly of ethyl ester of 5”-cholesteryl-phosphonyl zidovudine (ECPZ)
An amphiphilic prodrug of anti-HIV nucleoside analogue,ethyl ester of 5’-cholesteryl-phosphonyl zidovudine (ECPZ) was synthesized.An aqueous suspension containing ECPZ self-assemblies was obtained through injecting the THF solution of ECPZ into water under agitation.Hydrophobic interaction may be the driving force of molecular self-assembly.The self-assemblies were nanoscale with ~130 nm in size,and remained stable for a long time.Degradation of ECPZ self-assemblies were investigated in various environments including buffered solutions,plasma and tissue homogenates.ECPZ was degraded very slowly in neutral solutions,but rapidly degraded quickly in acid solution with the half-lives (t1/2) of less than 20 h.ECPZ self-assemblies showed potent anti-HIV activity on MT4 cell model.And the anti-HIV 50% effective concentration (EC50) of CPZ self-assemblies was 1 nM,only equal to 1/10 of AZT EC50 in the condition of ECPZ and HIV virus added into cells simultaneously,and 1/50 of AZT EC50 in the condition of ECPZ added into cells first,then added with virus.ECPZ was rapidly eliminated from circulation and distributed into the mononuclear phagocyte system (MPS) including liver,spleen and lung after bolus intravenous administration of ECPZ self-assemblies.The MPS-targeted effect and high anti-HIV activity of ECPZ self-assemblies make them become a promising self-assembled drug delivery system (SADDS) to eradicate HIV hidden in MPS.
anti-HIV cholesterol phosphorylation prodrugs self-assembly zidovudine (AZT)
Lina Du Junwei Jia Pingju Ge Yu Wang Miao Li Xin Li Yiguang Jin
Department of Pharmaceutical Chemistry,Beijing Institute of Radiation Medicine,Beijing 100850,P. R. Department of Pharmaceutical Chemistry,Beijing Institute of Radiation Medicine,Beijing 100850,P. R. Department of Pharmacy,Chinese PLA General Hospital,Beijing 100853,P. R. China
国内会议
南京
英文
1-29
2014-06-10（万方平台首次上网日期，不代表论文的发表时间）