Study On Oleanolic Nanoparticles As Liver-targeted Drug Delivery System

Objective: In order to prepared acid loaded Poly lactic acid-glycolic acid copolymernanoparticles, the oleanolic acid Poly lactic acid-glycolic acid copolymer nanoparticlesoptimized formulation were established. The molding process of freeze-dried preparationswere investigated preliminary, and with respectively to their in vitro drug release and the invivo animal experiment.Method: On the basis of preliminary experiments, the carriers and the preparationmethods of preparation oleanolic acid nanoparticles were preferred. And the encapsulationefficiency was as evaluation index to investigate the surfactant types, the ratio of theorganic and aqueous, the organic phase to join the water phase speed etc. According to theresult, the orthogonal design was used to optimize the prescription of oleanolic acid PLGAnanoparticles.we took the dosage of OA, the dosage of PLGA, the dosage of HS15as maininfluencing factors with three levels respectively, thus optimization OA-PLGA-NPpreparation prescription. By freezing and drying technology to observe after freeze-driedpreparation and to choice appearance, colour and distribution as index optimizationnanoparticles optimization freeze-drying prescription and process. Investigation the vitrorelease of oleanolic acid manoparticles, concentration of OA can check by HPLC fromdifferent types release of media and to select the best release of the medium. The mice wereintravenous injection respectively OA and OA-PLGA-NP at a single dose of10.5mg/kg.The sample were got at different time, and the concentration of OA was calculated byinternal standard method. Selecting the peak concentration ratio(Ce), relative uptake rate(re)as evaluation indexes and to evaluate the targeting feature of OA-PLGA-NP in mice.Results: The nanoparticles were prepared by nano-precipitation method, and finallydetermined the optimal prescription as follows: PLGA usage is210mg, HS15usage is250 mg, OA dosage60mg. Under conditions of the optimization, the particles distribution ofOA-PLGA-NP was uniform, and the average diameter was (129±5)nm. Its encapsulationefficiency was (88.64±0.92)%. According to freeze drying experiment,15%sucrose mayhave the best protection as the protective effect. The powder was studied and the resultsindicated that the powder is stability such as particle size, pH, appearance, encapsulationefficiency, etc. The freeze-dried powder of OA-PLGA-NP didn’t change evidently in4℃or37℃(relative humidity75%) after storage of three months. In vitro of drug release testshowed that different releasing models were examined for the cumulative releasingpercentage with to judge the correlation coefficient R2and we found that the releasingcurve of-OA-PLGA-NP was fit First-order kinetics. The vivo animals experiments showthat OA-PLGA-NP was injected into the mice can change its in the bodydistribution,compared with the OA, and Ceof OA-PLGA-NP is105.12, reis55.36, whichshow that the OA-PLGA-NP can extensively distributed in the liver.Conclusion: PLGA as a carrier preparation OA-PLGA-NP can change the distributionof the drug in the body, and to improve its bioavailability. The previous expectation hasbeen accomplished to have a liver targeting.