Development of Chitosan-Based pH-Sensitive Polymeric Micelles Containing Curcumin for Colon-Targeted Drug Delivery

作者：Woraphatphadung Thisirak; Sajomsang Warayuth; Rojanarata Theerasak; Ngawhirunpat Tanasait; Tonglairoum Prasopchai; Opanasopit Praneet^*

来源：AAPS PHARMSCITECH, 2018, 19(3): 991-1000.

DOI：10.1208/s12249-017-0906-y

• pH-sensitive polymeric micelles
• curcumin
• NSCS
• OSCS
• oral colon-targeted drug delivery

pH-sensitive N-naphthyl-N,O-succinyl chitosan (NSCS) and N-octyl-N,O-succinyl chitosan (OSCS) polymeric micelles carriers have been developed to incorporate curcumin (CUR) for colon-targeted drug delivery. The physical entrapment methods (dialysis, coAsolvent evaporation, dropping, and O/W emulsion) were applied. The CUR-loaded micelles prepared by the dialysis method presented the highest loading capacity. Increasing initial amount of CUR from 5 to 40 wt% to polymer resulted in the increase in loading capacity of the polymeric micelles. Among the hydrophobic cores, there were no significant differences in the loading capacity of CUR-loaded micelles. The particle sizes of all CUR-loaded micelles were in the range of 120-338 nm. The morphology of the micelles changed after being contacted with medium with different pH values, confirming the pH-responsive properties of the micelles. The release characteristics of curcumin from all CUR-loaded micelles were pH-dependent. The percent cumulative release of curcumin from all CUR-loaded micelles in simulated gastric fluid (SGF) was limited to about 20%. However, the release amount was significantly increased after contacted with simulated intestinal fluid (SIF) (50-55%) and simulated colonic fluid (SCF) (60-70%). The released amount in SIF and SCF was significantly greater than the release of CUR from CUR powder. CUR-loaded NSCS exhibited the highest anti-cancer activity against HT-29 colorectal cancer cells. The stability studies indicated that all CUR-loaded micelles were stable for at least 90 days. Therefore, the colon targeted, pH-sensitive NSCS micelles may have potential to be a prospective candidate for curcumin delivery to the colon.

• 出版日期2018-4