Research On Curcumin-Loaded PLGA-PEG-PLGA Micelles

Curcumin is a yellow colored polyphenol with anticancer, anti-inflammatory, anti-virus and antioxidant activities. Its low water solubility, unstablity, quick metabolism and lower bioavailability limited its development and usage. So, how to overcome its shortcoming and improve curcumin's bioavailability and reduce its dosage has been an urgent problem to resolve for researchers.Amphipathic copolymer composed of hydrophilic and hydrophobic segment can self-assemble to form micelle with core-shell structure. Hydrophilic chain segment can prevent the touch of drug and water, stabilize copolymer micelle and avoid identification of reticuloendothilial system in body. Hydrophobic segment can provide hydrophobic microenviroment to increase the solubility of water insoluble drug in water. This micelle is able to raise drug's water-solubility, improve release property and obtain drug's target controlled-release.PLGA-PEG-PLGA block-copolymer was synthesized by ring-openning polymerization of PEG, lactide and glycolide with stannous ocatate as catalyst, and its structure was characterized. Then, preparation process and quantitative analysis of curcumin-loaded micelle were studied, and block-copolymer's CMC, particle diameter distribution of blank and drug-loaded micelle and Zeta potential, micromophology and in vitro release behavior of drug-loaded micelle were also determined. CUR's extracion from plama and tissues in mice and HPLC quantitative methodology were constructed, and in vivo pharmacokinetics and distributions of curcumin in tissues were researched. The results demonstrated that mean entrapment efficiency, mean drug-loading rate, mean particle parameter, solubility in water and zeta potential of CUR-loaded micelle prepared by water dialysis were 70.03±0.34%,6.4±0.02%,26.29nm, 1.47mg/ml and-0.71mV, respectively. The in vitro release showed that the release of CUR from micelle was in line with ambiexponent and biphasic kinetics equation, showing property of burst release earlier followed slow release.In vivo pharmacokenetics study showed that area under drug-time curve, mean retention time (MRT), elimination half-time and distribution half-time were 1.31 fold,2.67 fold,2.48 fold and 4.54 fold these of the control formulation, respectively. Additionally, plasma total body clearance and peak concentration were also decreased. The prolongation of MRT and decrease of total body clearance hinted that CUR-loaded micelle could lengthen curcumin's action time in vivo.The study on tissue distribution in vivo indicated that Ce, RUE and RTE for brain and lung were 2.00 and 1.02,14.31 and 5.56, and 247.22% and 34.72%, respectively, showing that CUR-loaded micelle could obviously improve distribution and gathering of curcumin in brain and lung.