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  • Title: Self-assembled drug delivery systems. Part 4. In vitro/in vivo studies of the self-assemblies of cholesteryl-phosphonyl zidovudine.
    Author: Jin Y, Xing L, Tian Y, Li M, Gao C, Du L, Dong J, Chen H.
    Journal: Int J Pharm; 2009 Oct 20; 381(1):40-8. PubMed ID: 19646518.
    Abstract:
    An amphiphilic prodrug of anti-HIV nucleoside analogue, cholesteryl-phosphonyl zidovudine (CPNZ) was synthesized. An aqueous suspension containing CPNZ self-assemblies was obtained through injecting the ethanol solution of CPNZ and cholesteryl succinyl poly(ethylene glycol) 1500 (20:1, mol/mol) into water under agitation. Hydrophobic interaction may be the driving force of molecular self-assembly. The self-assemblies were nanoscale with approximately 100nm in size, and remained stable for a long time. Degradation of CPNZ self-assemblies was investigated in various environments including buffered solutions, plasma and rabbit tissue homogenates. CPNZ was degraded very slowly in neutral solutions but rapidly in various plasma with the half-lives (t(1/2)) of less than 20h. Tissue homogenates degraded CPNZ with varied rates depending on enzyme activity. CPNZ self-assemblies showed potent anti-HIV activity on MT4 cell model, the anti-HIV 50% effective concentration (EC(50)) of which was 1nM, only equal to 1/5 of AZT EC(50). CPNZ was rapidly eliminated from circulation and distributed into the mononuclear phagocyte system (MPS) including liver, spleen and lung after bolus intravenous administration of CPNZ self-assemblies followed slowly elimination. The possible products include AZT-5'-H-phosphonate, AZT and their derivatives. The MPS-targeted effect and high anti-HIV activity of CPNZ self-assemblies make them become a promising self-assembled drug delivery system (SADDS).
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