Anticancer effect of atorvastatin nanostructured polymeric micelles based on stearyl-grafted chitosan

作者：Mekhail George M; Kamel Amany O; Awad Gehanne A S; Mortada Nahed D^*

来源：International Journal of Biological Macromolecules, 2012, 51(4): 351-363.

DOI：10.1016/j.ijbiomac.2012.05.026

• Atorvastatin
• Synthesis
• Stearyl-grafted chitosan
• Polymeric micelles
• MCF 7
• HCT 116

The purpose of this study was to develop a new therapeutic approach for atorvastatiri (ATV) adopting nanostructured polymeric micelles for its controlled delivery to the cancer cells. Amphiphilic block copolymers of stearyl chitosan (SC) and sulfated stearyl chitosan (S-SC) that could self assemble to form polymeric micelles with different degree of substitution (DS) were synthesized and characterized. The synthesized chitosan derivatives were able to self assemble and form micelles encapsulating ATV with critical micellar concentrations ranging from 6.9 to 21 mu g/ml, drug-loading ranging from 40% to 84.1% and encapsulation efficiency ranging from 10.4% to 35%. ATV caused a significant decrease in particle size and zeta potential of both SC and S-SC micelles. Micelles encapsulating ATV exhibited a sustained release and more cytotoxic activity against MCF 7 and HCT 116 cell lines than ATV alone. The 50% cellular growth inhibition (IC50%) of the drug decreased from 10.4 to 3.7 in case of MCF 7 and from 9.4 to 3.4 in case of HCT 116 after its loading in micelles. These results indicate that SC ATV polymeric micelles can be considered as a promising system for site specific controlled delivery of ATV to tumor cells.

• 出版日期2012-11