Effect of structural factors on release profiles of camptothecin from block copolymer conjugates with high load of drug.

The aim of the present work was the synthesis and study the kinetics and profiles of camptothecin (CPT) release form block co- and ter-polymer conjugates comprising polylactide (PLA) segments and CPT moieties, structurally diverse by degrees of branching, content of d-PLA units and poly(ethylene glycol) methyl ether methacrylate (PEGMA). Six PLA, non-toxic macroinitiators (MIs), terminated with α-bromoester were synthesized. MIs were subjected to polymerization of CPT methacrylic derivative (CPTMA) with PEGMA at various ratios. The average contents of CPT from elemental analysis, NMR and UV-GPC were approximate to each other. The number of CPT molecules and PEGMA units was in the range of 9-195 and 0-280 per conjugate, respectively. PEGMA units plasticized PLA causing increase of its crystallinity, whereas 7% and more of d-PLA caused material amorphous. PEGMA units decreased thermal stability of conjugates, however it compatibillized the separated phases of PLA and PCPTMA, based on AFM. In vitro release rate of CPT from linear PLA conjugates deposited on injection-molded PLA bars increased by introduction of PEGMA units with zero-order kinetics and Korsmeyer-Peppas model indicating the super case II transport. Branched conjugates revealed some burst release and then the release was rather of first-order-kinetics with respect to CPT with non-Fickian transport.