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Design Of Chitosan-alginate Nanoparticles Containing Curcumin Diethyl Disuccinate |
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| รหัสดีโอไอ | |
| Title | Design Of Chitosan-alginate Nanoparticles Containing Curcumin Diethyl Disuccinate |
| Creator | Settapon Bhunchu |
| Contributor | Pranee Rojsitthisak, Pornchai Rojsitthisak |
| Publisher | Chulalongkorn University |
| Publication Year | 2558 |
| Keyword | Nanoparticles, Chitosan, Curcumin |
| Abstract | Curcumin diethyl disuccinate (CDD) is a succinate prodrug of curcuminoids that has better stability in human plasma and improved in vitro cellular uptake and cytotoxicity compared to curcumin and other succinate prodrugs. Therefore, CDD has a potential for further development as an anticancer agent. In this study, we focuses on optimization of the formulation of CDD-loaded chitosan/alginate nanoparticles using Box-Behnken statistical design and response surface methodology to enhance the therapeutic efficacy of CDD. Oil-in-water emulsification followed by ionotropic gelification was used to prepare the CDD-loaded nanoparticles. One-variable-at-a-time approach was used as a parameter screening technique and pre-optimization for CDD-loaded nanoparticles. The chitosan/alginate mass ratio, and concentrations of Pluronic® F127 and CDD were the major affecting parameters. The pre-optimaized formulation of nanoparticles was a chitosan/alginate mass ratio of 0.15:1, a Pluronic® F127 concentration of 1% (w/v) and a CDD concentration of 1 mg/ml. The pre-optimized CDD-loaded nanoparticles could stored at 4oC up to 3 months. In addition, the CDD-loaded nanoparticles showed significantly higher cellular uptake in Caco-2 cell line compared to free CDD. To determine the interaction among the parameters, the Box-Behnken experimental design and response surface methodology were used to design and optimize the CDD-Nanoparticles with two types of non-ionic surfactants including Tween® 80 and Pluronic® F127. The optimized formulation of CDD-loaded chitosan/alginate nanoparticles based on Tween® 80 was chitosan/alginate mass ratio of 0.05:1, Tween® 80 concentration of 4.05% (w/v) and CDD concentration of 3 mg/ml. On the other hand, the optimalized formulation based on Pluronic® F127 was chitosan/alginate mass ratio of 0.05:1, Pluronic® F127 content of 0.65% (w/v) and CDD concentration of 1.5 mg/ml. The encapsulation of CDD in the nanoparticles was confirmed using FTIR, TGA and XRD. . In vitro cytotoxicity and cellular uptake studies showed that CDD-loaded chitosan/alginate nanoparticles using Pluronic® F127 as a stabilizer had significantly higher cytotoxicity and cellular uptake in human breast adenocarcinoma MDA-MB-231 cells, compared to free CDD. Physical and chemical stability studies indicated that the optimally formulated CDD-loaded chitosan/alginate nanoparticles were stable at 4oC for 3 months. |
| URL Website | cuir.car.chula.ac.th |
