Construction Stdudies On Biotinylated Liposomes As Potential Carries For Enchanced Oral Absorption Of Curcumin

Curcumin,1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-d ione,is a nature yellow hydrophobic polyphenol,can be extract from the rhizomes of curcuma longa.Due to its remarkable Pharmacological activities of anti-carcinogenic effect,anti-inflammatory effect,anti-HIV activity,anti-oxidant activity and apoptosis induction,curcumin has been broadly applied to cancer treatment.As a promising anticancer drug,Curcumin has attracted people's attention in cancer prevention and treatment and has listed one of the third generation cancer chemopreventive agent by the US National Cancer Institute.Because curcumin undergoes rapid metabolism and clearance when administered,it has very poor bioavailability.In a world,the therapeutic application of curcumin is limited because of its poor solubility and low bioavailability.Liposome encapsulation technique can be employed to solve the problem that fat-soluble drugs cannot be easily dissolved in water.Liposome is also an ideal carrier of anti-tumor drugs.However delivering anticancer drug orally often leads to a low bioavailability owing to first-pass effect and barriers to physical absorption in the eptithelium.We desire to develop biotin-decorated liposomes to enhance the oral absorption of curcumin by biotin receptor-mediated endocytosis targeted to the intestinal epithelia,and to explore and clarify the mechanisms.Three different liposomes were prepared by thin film dispersed method and the content of curcumin was determined by HPLC.The preparation was carried out by orthogonal test and the entrapment efficiency and loading capacity of curcumin were used as indexes.Then the particle size,Zeta potention and vitro release were determined.The intestine in rat was cannulated to study the absorption mechanism of curcumin liposomes and the result as a index to determine the amount of Biotin-PEG-DSPE.The Caco-2 cell monolayer model were also used to determined the absorption mechanism of curcumin.The pre-formulation studies of curcumin liposomes were analyzed and the curcumin liposomes was separated by Sephadex G50 to measure the entrapment efficiency.In the single factor test,we found the ratio of drug to lipid was the most influence factor of entrapment efficiency.According to the orthogonal experimental design,the optimum prescription ptimum prescription was showed as followed: CuR 5 mg,lecithin 100 mg,cholesterol 40 mg,hydration temperature 45 oC,5% glucose as the hydration medium.The absorption effect of Biotin-PEG-Bintio-Lip was better than DSPE-PEG-Lip in the experiment of rat single pass intestinal perfusion?cell uptake and Caco-2 cell transport,which proved that with biotin as targeting ligands achieved to a high oral absorption of curcumin.