Preparation, Characterization And Pharmacodynamic Study Of UA Nanoliposomes

Ursolic acid (UA), a natural pentacyclic triterpenoid compound widely distributing inplant kingdom, UA exerts a wide range of biological activities, especially its antitumoractivity attracts more attention. However, its poor aqueous solubility limits the applicationin the clinical. In order to improve the bioavailability of UA, liposomes were used asnanoscale drug carriers to reduce side effects and improve the curative effect. However,the conventional liposomes still have the problem of short cycle time, easily to be clearedby the immune system and a high drug leakage rate. In this study, in order to overcome theabove defects, prolong the circulation time in vivo and improve circulationstability, further modified liposomes with polyethylene glycol (PEG) and chitosan (CS)respectively were prepared, so that the drug can more fully play its role. We wrappedursolic acid into liposomes using an effective ethanol injection method, and orthogonalexperiment was designed to optimize the preparation process parameters, and furtherexamine the morphology of the prepared liposome, stability and release efficiency,cytotoxicity and in vivo anti-tumor effect.The optimum process parameters for the preparation of ursolic acid liposomes wereas follows: the optimal weight ratio of soybean lecithin to ursolic acid, cholesterol andpolyethylene glycol were10:1,6:1and15:1respectively, and the ideal hydrationtemperature was50°C. The obtained liposomes encapsulation efficiency was90.7%measured by HPLC. The images of atomic force microscopy and transmission electronmicroscopy indicated that liposomes were nearly spherical, with a uniform sizedistribution with diameters near100-200nm and good dispersibility. The result of fouriertransform infrared spectroscopy (FTIR) showed that PEG anchored the liposomessuccessfully. In vitro release study reflected that liposomes with PEG and CS displayedslower release rate than conventional liposomes, the sustained release effects were obvious;In view of the microtiter tetrazolium (MTT) results, conventional UA liposomes exhibiteda better inhibitory effect against ECV-304cells compared with that of modified UAliposomes, markedly higher than the group of ursolic acid solution, while chitosan coated liposomes showed greater cytotoxicity than that of conventional UA liposomes, whichindicated that after UA wrapped into liposomes, the growth inhibition of UA wassignificantly enhanced. The results of vivo test in mice also showed that liposomesmodified with PEG and CS enhanced the UA concentration in the tumor tissue andobtained a higher inhibition rates, resulting in a large number of cancer cell apoptosis, andexhibited better anti-tumor effects, which also laid the theoretical foundation for the studyof new forms of UA drugs.