SN-38-Loaded PLGA microspheres injected intratumorally for cancer: preparation, characterization and evaluation

Abstract

7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite with broad spectrum cytotoxic activity produced by 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11), has been shown to be useful in the treatment of various tumors. The aim of this research was to develop SN-38 loaded PLGA microspheres (SN-38-PLGA-MS) to extend retention time of SN-38 in tumor and reduce its concentrations in plasma, thereby to improve therapeutic efficacy and reduce side effects. The SN-38-PLGA-MS was prepared by emulsion-solvent evaporation method at a molar ratio of 1:10 (SN-38: PLGA). Tumor retention and plasma leakage were assessed by measuring drug concentrations in tumor sites and plasma at different time points. The therapeutic effect of SN-38-PLGA-MS was further evaluated by pharmacodynamic studies and histological analysis. The freeze-dried microspheres can effectively prolong the retention time of SN-38 in tumor site from 144 h to 432 h, which was 3.00 times than SN-38 solution. The in vivo pharmacodynamic results revealed that SN-38-PLGA-MS significantly improved the inhibition of tumor cell growth. In summary, SN-38-PLGA-MS was proved as a promising carrier for inhibiting tumor cell proliferation, and had important clinical value in the treatment of tumors.