Self-assembled drug delivery systems

Add time:07/27/2019    Source:sciencedirect.com

Self-assembled drug delivery systems (SADDS) are defined as the self-assemblies of amphiphilic prodrugs, integrating prodrugs, molecular self-assembly and nanotechnology for drug targeting and controlled release. Cholesteryl-succinyl didanosine (CSD) and cholesteryl-adipoyl didanosine (CAD) nanoparticulate systems in water were previously prepared and optimized. In this paper, the in vitro and in vivo behavior of them was investigated. Precipitation occurred when they were mixed with acid solutions due to rapid production of hypoxanthine and subsequent disruption of supramolecular structures. They showed pH-dependent degradation and kept relatively stable in the neutral pH range. CSD is more stable than CAD due to the shorter spacer and poloxamer protection. CSD showed different degradation rates in various plasma with the descending order of rat, mouse, rabbit, dog and human. The half-life (t1/2) of CSD is 9 days in rat plasma, and 5.9 days in rat liver homogenates. CAD has a faster degradation than CSD though the t1/2 in rat liver homogenates is long to 23 h. CSD nanoparticulates showed no significant anti-HIV effect in MT4 cell model because of very slow degradation. CSD nanoparticulates showed the distribution t1/2 of 7.6 min after bolus intravenous (i.v.) administration to rats, and the site-specific distribution in liver, lung and spleen with the high t1/2 of 10 days in liver. The factors affecting achievement of successful SADDS are discussed.

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