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 similar to 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.