Synthesis, characterization, and evaluation of mPEG–SN38 and mPEG–PLA–SN38 micelles for cancer therapy

7-Ethyl-10-hydroxy camptothecin (SN38) is a potent topoisomerase inhibitor and a metabolite of irinotecan. Its clinical development has been hampered by its poor solubility. To address this problem, methoxy poly(ethylene glycol)-2000 (mPEG(2K))–SN38 and mPEG(2K)–poly(lactide) (PLA(1.5K))–SN38 conjugates were prepared and then dispersed into an aqueous medium to form micelles. Physicochemical characteristics of SN38–polymer conjugate micelles, for example, micelle diameter, zeta potential, morphology, and drug content, were then evaluated. The results showed that the mean diameters of mPEG(2K)–SN38 and mPEG(2K)–PLA(1.5K)–SN38 micelles were ~130 and 20 nm, respectively. These two micelles had similar drug contents. mPEG(2K)–PLA(1.5K)–SN38 micelles were more homogeneous than mPEG(2K)–SN38 micelles. Moreover, in vitro drug release behavior of the micelles was studied by high performance liquid chromatography. SN38 release from mPEG(2K)–SN38 micelles was much faster than from mPEG(2K)–PLA(1.5K)–SN38 micelles. In vitro cytotoxicity, cellular uptake, and apoptosis assays of the SN38–polymer conjugate micelles were carried out on BEL-7402 human liver cancer cells. In vivo biodistribution and antitumor tumor efficacy studies were carried out in a nude mouse xenograft model derived from BEL-7402 cells. The results showed that mPEG(2K)–PLA(1.5K)–SN38 micelles were significantly more effective than mPEG(2K)–SN38 micelles in tumor inhibition, and the inhibitory effect of mPEG(2K)–PLA(1.5K)–SN38 micelles on tumor growth was significantly greater than that of mPEG(2K)–SN38 micelles (1,042 vs 1,837 mm) at 30 days. In conclusion, mPEG–PLA–SN38 is a promising anticancer agent that warrants further investigation.