This work aims to improve the solubility of 7-ethyl-14-aminocamptothecin (EACPT) by encapsulating it into monomethoxy poly(ethylene glycol)2000 -poly(lactic acid)2000 (MPEG-PLA) polymeric micelles. Micelles were prepared by a solid dispersion method; the properties including particle size distribution, morphology, drug loading, entrapment efficiency, crystallography property, solubility, and stability were characterized in detail. The results demonstrated that the EACPT-loaded MPEG-PLA polymeric micelle (EACPT-M) was successfully developed with a small particle size of 20.7 ± 0.2 nm, and the solubility was increased approximately 800-fold compared with free drug. In vitro release study showed sustained-release behavior of EACPT-M. Cytotoxicity assay suggested the incorporated EACPT maintained the potent antitumor effect of free drug. Furthermore, the obtained EACPT-M (1 mg/mL) did not induce hemolysis in vitro. Additionally, EACPT-M exhibited significant tumor growth inhibition in H460 human tumor xenograft model. The results indicated that the EACPT-M was a water-soluble, safe, and effective delivery system for human cancer chemotherapy.
Keywords: 7-ethyl-14-aminocamptothecin; PLA; cancer chemotherapy; micelle; solid dispersion; solubility.
© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.