Preparation of Curcumin-loaded Polymeric micelles for Oral Colon-Targeted Drug Delivery
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Abstract
Introduction: Curcumin is an anticancer agent to use in chemoprevention and treatment colorectal cancer. However, one problem of curcumin is its low solubility. Polymeric micelles has been designed for entrapment of hydrophobic drugs to improve drug solubility. Thus, this study aimed to investigate entrapment efficiency of curcumin-loaded N-octyl-N,O-succinyl chitosan (OSCS) polymeric micelles, characterization and control drug release at colon targeted site by oral route. Methods: The OSCS micelles were prepared to load curcumin. The physical entrapment methods (dialysis and evaporation) were applied. Curcumin-loaded OSCS micelles were determined loading efficiency, loading capacity, particle size, in vitro cytotoxicity and in vitro drug release. Results: The OSCS micelles were able to load curcumin in the hydrophobic inner core by dialysis and evaporation methods. The curcumin-loaded OSCS micelles by dialysis method showed loading efficiency (22.75±5.54%) and loading capacity (78.42±5.94 μg/mg) higher than evaporation method (loading efficiency 7.80±1.46%; loading capacity 15.59±2.91 μg/mg, respectively). The mean particle sizes of micelles by dialysis method were in the range of 193-260 nm which were smaller than that by evaporation method (310-354 nm). The cytotoxicity of OSCS micelles on Caco-2 cells depended on the concentration of OSCS with the IC50 value of 2.95±0.06 mg/mL. The cumulative release of curcumin from OSCS micelles in simulated gastric fluid (SGF) was about 20%. When pH medium was changed to pH 6.8 (simulated intestinal fluid; SIF) and pH 7.4 (simulated colonic fluid; SCF), the curcumin release was significantly increased (SIF; 50-55%) and (SCF; 60-70%) when compared to curcumin free drug (20%) (p<0.05). Conclusion: These finding supports the potential of these pHsensitive OSCS polymeric micelles and it might be improved solubility of hydrophobic drugs and control drug release at colon targeted site by oral administration.
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