Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan as self-assembled micelles carriers for osthole.

Abstract

Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA-TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with sizes ranging from 136 nm to 212 nm. The critical aggregation concentration increased from 0.6 mg • L(-1) to 88 mg • L(-1) with decrease in the degree of CA substitution. Osthole (OST) could be easily encapsulated into the CA-TMC micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy results show that OST/CA-TMC micelles have significant antitumor activity on Hela and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7 μg. mL(-1), respectively. Cell apoptosis was the main effect on cell death of Hela and MCF-7 cells after OST administration. The blank micelles did not affect apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7 cells and could localize in the cell nuclei. These findings suggest that CA-TMC micelles are promising carriers for OST delivery in cancer therapy.

• Authors: Xiao-juan Hu, Yang Liu, Xiao-feng Zhou, Qiao-ling Zhu, Yong-yan Bei, Ben-gang You, Chun-ge Zhang, Wei-liang Chen, Zhou-li Wang, Ai-jun Zhu, Xue-nong Zhang, Yu-jiang Fan
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 8 Pg. 3543-58 ( 2013) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 24106424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Coumarins
• Micelles
• Nanocapsules
• Chitosan
• osthol

Topics

• Antineoplastic Agents (administration & dosage, adverse effects, chemistry)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Chitosan (chemistry)
• Coumarins (administration & dosage, adverse effects, chemistry)
• Diffusion
• Drug Compounding
• Humans
• Micelles
• Nanocapsules (chemistry, ultrastructure)
• Neoplasms, Experimental (drug therapy, pathology)
• Particle Size
• Treatment Outcome