The Preparation Of Oleanolic Acid Long Circulation Liposomes And Targeted Research

Objective: Oleanolic acid is possessing many pharmacological activities,such as Protect liver and kidney,anti-inflammatory,fall hematic fat and blood sugar,and so on.Oleanolic acid is commonly used in the therapy of hepatitis in clinic and remarkably improve the symptom,physical sign and hepatic function of hepatopath.Now there are only granules capsule oral tablet of oleanolic acid in market and because of its poorly solubility in water,the oral administration of oleanolic acid often results in low bioavailability.In order to prolong the resident time of oleanolic acid in the blood circulating system,and has a prolonged action,phospholipid and cholesterol were used as carrier materials to optimize prescription and preparation technology of oleanolic acid liposomes.To investigate oleanolic acid long circulation liposomes in vivo pharmacokinetics behavior in rats.Methods: On the basis of preliminary experiments,the preparation methods of preparation oleanolic acid long-circulation Liposomes were preferred.Liposomes were prepared by thin-film ultrasonic dispersion method,and the content of oleanolic acid was determined by HPLC.With the entrapment efficiency as index,prescription and process were optimized by central composite design-response surface methodology.The concentration of oleanolic acid in rats plasma was determined by HPLC method and the parameters were calculated with DAS2.0 program.Results: The optimum prescription and process conditions were as follows;the mass ratio of lecithin and cholesterol is 31:5;the mass ratio of lecithin and oleanolic acid is 34:5;ultrasound vibration for 40 min.The average particle size of liposomes was 312 nm,and the entrapment efficiency was 89.89 %.The pharmacokinetic parameters of the three kinds of Oleanolic acid long circulation liposomes were4797.03 and 4536.53 and 4819.69 ?g·min·ml-1for AUC,148.35 and 135.15 and162.98 min for t1/2.The average was about 3 times and 1.5 times of conventional liposomes and oleanolic acid solution,respectively.The average was about 2.5 times and 1.5 times of conventional liposomes and oleanolic acid solution,respectively.For each drug concentration in the organization order: liver > heart > blood > lung >spleen > kidney.Conclusion: The craft was feasible,stable and applicable for the production of OA long circulation liposomes.Compared with conventional liposomes and oleanolic acid solution,the oleanolic acid long circulation liposomes can significantly prolong the resident time of oleanolic acid in the blood circulating system,and has a prolonged action.