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

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Abstract

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, co­solvent 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.

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Acknowledgements

This research was supported by the Commission of Higher Education (Thailand), the Thailand Research Fund through the Golden Jubilee Ph.D. Program (Grant No. PHD/0027/2556), the Thailand Research Fund, the National Nature Science Foundation of China (NSFC), and the Silpakorn University Research and Development Institute.

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Authors and Affiliations

  1. Pharmaceutical Development of Green Innovations Group (PDGIG) Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand

    Thisirak Woraphatphadung, Theerasak Rojanarata, Tanasait Ngawhirunpat, Prasopchai Tonglairoum & Praneet Opanasopit

  2. National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani, 12120, Thailand

    Warayuth Sajomsang

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  1. Thisirak Woraphatphadung
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  2. Warayuth Sajomsang
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  4. Tanasait Ngawhirunpat
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Correspondence to Praneet Opanasopit.

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Woraphatphadung, T., Sajomsang, W., Rojanarata, T. et al. Development of Chitosan-Based pH-Sensitive Polymeric Micelles Containing Curcumin for Colon-Targeted Drug Delivery. AAPS PharmSciTech 19, 991–1000 (2018). https://doi.org/10.1208/s12249-017-0906-y

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  • DOI: https://doi.org/10.1208/s12249-017-0906-y

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