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dc.contributor.authorWarayuth Sajomsangen_US
dc.contributor.authorPattarapond Gonilen_US
dc.contributor.authorSomsak Saesooen_US
dc.contributor.authorUracha Rangsadthong Ruktanonchaien_US
dc.contributor.authorWanwisa Srinuanchaien_US
dc.contributor.authorSatit Puttipipatkhachornen_US
dc.contributor.otherThailand National Science and Technology Development Agencyen_US
dc.contributor.otherMahidol Universityen_US
dc.identifier.citationInternational Journal of Pharmaceutics. Vol.477, No.1-2 (2014), 261-272en_US
dc.description.abstract© 2014 Elsevier B.V. All rights reserved. Curcumin (CM) has demonstrated safety and efficacy as a drug, but its pharmaceutical role is restricted as a result of extremely low aqueous solubility, rapid systemic elimination, inadequate tissue absorption and degradation at alkaline pH; properties that severely curtail its bioavailability. To address this issue, CM was encapsulated within pH responsive amphiphilic chitosan, resulting in the formation of 100 nm spontaneously self-assembled polymeric micelles in water. The amphiphilic chitosan, namely N-benzyl-N,O-succinyl chitosan (BSCS), was prepared by reductive N-benzylation and N,O-succinylation. The stability of micelles after being re-dispersed in water was investigated using glycine as a cryoprotectant, and the average sizes were shown to be maintained at a level lower than 200 nm for up to 4 months, at temperatures of 4 °C and 25°C. In vitro drug release results showed that CM was slowly released from the micelles without any burst effect in the intestine (pH 5.5-7.4), with limited release in the stomach (pH 1.2). Cytotoxicity assays indicated that CM loaded micelles showed half maximal inhibitory concentrations (IC<inf>50</inf>) 4.7-, 3.6-, and 12.2-fold lower than that of free CM in HeLa, SiHa and C33a cervical cell lines, respectively. Cellular uptake of micelles was confirmed by confocal laser scanning microscopy and flow cytometry, with a 6-fold significant increase in the amount of CM loaded micelles compared to free CM in all cervical cancer cells. Notably, CM loaded micelles promoted an increase (30-55%) in the percentage of early apoptosis of HeLa, SiHa and C33a cells, compared to free CM. These results suggest that BSCS micelles may be a promising carrier for effective oral delivery of CM.en_US
dc.rightsMahidol Universityen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleSynthesis and anticervical cancer activity of novel pH responsive micelles for oral curcumin deliveryen_US
Appears in Collections:Scopus 2011-2015

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