In vitro antitumour activity of stearic acid-g-chitosan oligosaccharide polymeric micelles loading podophyllotoxin.

Development of successful formulations for poorly water-soluble drugs remains a longstanding critical and challenging issue in cancer therapy. The stearic acid-g-chitosan oligosaccharide (CSO-SA) micelles have been presented as potential candidates for intracellular antitumour agent delivery carrier. Herein, podophyllotoxin (PPT) loaded CSO-SA micelles (CSO-SA/PPT) were prepared by a dialysis method. The drug encapsulation efficiency could reach a higher level, the micellar size and the zeta potential increased with increasing charged amounts of drug. The cumulative release percentage of PPT drug from micelles enhanced with decreasing PPT content in the micelles. The cytotoxicities of CSO-SA/PPT micelles against human breast carcinoma (MCF-7) cells, human lung cancer cells (A549) and human hepatoma cell line (Bel-7402) were higher than that of free PPT formulation. The higher cytotoxicities were due to the faster PPT transport into tumour cells mediated by CSO-SA micelles. Overall, CSO-SA micelles might be a promising carrier for PPT delivery in cancer therapy.

Effect of Podophyllotoxin Conjugated Stearic Acid Grafted Chitosan Oligosaccharide Micelle on Human Glioma Cells.

OBJECTIVE: To study the physiochemical characteristics of podophyllotoxin (PPT) conjugated stearic acid grafted chitosan oligosaccharide micelle (PPT-CSO-SA), and evaluate the ability of the potential antineoplastic effects against glioma cells. METHODS: PPT-CSO-SA was prepared by a dialysis method. The quality of PPT-CSO-SA including micellar size, zeta potential, drug encapsulation efficiency and drug release profiles was evaluated. Glioma cells were cultured and treated with PPT and PPT-CSO-SA. The ability of glioma cells to uptake PPT-CSO-SA was observed. The proliferation of glioma cells was determined by 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The apoptosis and morphology of U251 cells were observed by 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) dye staining. Cell cycle analysis was performed by flow cytometry. The migration ability of U251 cells was determined by wound healing test. RESULTS: PPT-CSO-SA had nano-level particle size and sustained release property. The encapsulation efficiency of drug reached a high level. The cellular uptake percentage of PPT in glioma cells was lower than that of PPT-CSO-SA (p<0.05). The inhibitory effect of PPT-CSO-SA on glioma cells proliferation was significantly stronger than that of PPT (p<0.05). The morphologic change of apoptosis cell such as shrinkage, karyorrhexis and karyopyknosis were observed. The percentage of U251 cells in G2/M phase increased significantly in the PPT-CSO-SA group compared with PPT group (p<0.05). Compared with the PPT group, the cell migration ability of the PPT-CSO-SA group was significantly inhibited after 12 and 24 hours (p<0.05). CONCLUSION: PPT-CSO-SA can effectively enhance the glioma cellular uptake of drugs, inhibit glioma cells proliferation and migration, induce G2/M phase arrest of them, and promote their apoptosis. It may be a promising anti-glioma nano-drug.