Influence of serum and albumins from different species on stability of camptothecin-loaded micelles.

Stability of CPT free drug and CPT-loaded polymeric micelles forming from poly (ethylene glycol)-poly (benzyl aspartate-69) block copolymer in the presence of serum and purified serum albumins were investigated by reverse-phase HPLC and GPC. The hydrolysis of CPT and CPT-loaded micelles follows pseudo-first-order kinetics. The observed hydrolysis rate constants for CPT and CPT-loaded micelles were 7.4x10(-3)min(-1) and 0.7x10(-3)h(-1), corresponding to an increase in half-life of CPT from 94 min to 990 h, respectively. The half-lives of CPT lactone hydrolysis of CPT-loaded micelles in the presence of BSA were significantly longer than the control whereas in the presence of HSA and serum was shorter than the control, and the similar results were obtained from GPC analyzed for micelles stability. This result suggested that the stability of CPT-loaded micelles was significantly decreased only in the presence of human albumin and serum. These were corresponded to the results of CPT free drug observed in the presence of albumins or serum. BSA significantly retarded the CPT lactone ring opening as compared with the control. On the other hand, HSA and serum showed rapid CPT lactone ring opening. This was probably due to preferential HSA binding to the carboxylate form resulting in a change in the lactone-carboxylate equilibrium, whereas, BSA did not bind to the lactone form, but might promote the self-aggregation of CPT and binding to the hydrophobic inner core of the micelles, resulting in enhanced stability of CPT-loaded micelles. MSA did not affect the stability of micelles.