Development of biodegradable polyesters with various microstructures for highly controlled release of epirubicin and cyclophosphamide.

In this study, "predominantly isotactic", disyndiotactic, and atactic polylactides (PLAs) and poly(ε-caprolactone)s (PCLs) were loaded with anticancer agents, epirubicin (EPI) and cyclophosphamide (CYCLOPHO), to investigate their properties as highly controlled delivery devices. It was found that the kinetic release of drugs from the obtained polyester matrices tested in vitro at 37°C and pH7.4 was strongly dependent on average molecular weight (Mn) of the polymers as well as the PLAs' microstructure. EPI and CYCLOPHO were released from various obtained matrices according to the diffusion, diffusion-degradation, and degradation mechanisms in a rather regular and continuous manner. Importantly, in some cases, the kinetics of the EPI and CYCLOPHO release was nearly zero-order, suggesting predominantly polymer degradation. It is shown that the drug release profiles can be tailored by a controlled design of the microstructure and Mn of polyesters, allowing use of the synthesized matrices for the development of highly controlled biodegradable anticancer drug delivery systems.