| Objective:To prepare three kinds of Oleanolic acid (OA)-loaded nanoparticles (NPs) using biodegradable polymer materials polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate (PLGA-TPGS),poly(ε-caprolactone)-polylactic acid-D-α-tocopher-ol polye-thylene glycol 1000 succinate (PCL-PLA-TPGS) made by ourselves and polylactic-co-glycolic acid (PLGA) purchased from Inc. Sigma as control, at the same time to establish their quality evaluating methods with encapsulation ratio(ER), drug loading(DL) and mean size. To find better NPs with the suitable drug loading, reasonable size and proper drug release in vitro that lays the foundation of targeting evaluation in liver. That improves OA effects on treatment of liver cancer and liver inflammation and so on.Methods:NPs were prepared by oil-water emulsion/solvent evaporation technique using PLGA, PLGA-TPGS and PCL-PLA-TPGS. Being based on the single-factor experiment, OA-NPs were prepared using orthogonal design for optimization of formulation and technology with ER, DL and mean size. The content of OA and in vitro drug release of OA-loaded nanoparticles were determined by RP-HPLC on HYPERSIL C18 column(4.6mm×250mm,5μm) with methanol-0.03% HOAc solution (90:10) as the mobile phase, and the detective wavelength was 210nm.Results:PLGA-NPs, PLGA-TPGS-NPs, PLC-PLA-TPGS-NPs were spherical with the mean size of 227.4nm±2.2nm,192.4nm±1.2nm, 214.2nm±1.6nm, the drug loading of 19.9%±1.4%,21.6%±1.0%, 20.2%±1.3% and the encapsulation ratio of 85.6%±4.9%,89.9%±4.3%, 87.7%±4.5% respectively. In vitro release behavior could be described by the Higuchi equation:Q=4.581t1/2+7.189(r=0.9867),Q=4.493t1/2+3.856 (r=0.9904),Q=4.358t1/2+3.528(r=0.9898) respectively. The in vitro drug release profile showed diphasic release pattern, and drug released quite entirely.Conclusions:The sizes of of OA-loaded-NPs made by ourselves accorded with the nanoparticles size requirement which is between 10nm and 1000nm, and the size distribution were symmetrical, the encapsulation ratio and drug loading were higher, and the in vitro experiments showed sustained release. We also need further research on whether the OA-loaded-NPs have the effect of liver targeting or not. If the in vivo study on the distribution of drug can prove both of the concentration of PLGA-TPGS-NPs and PLC-PLA-TPGS-NPs in liver are higher than that of PLGA-NPs in liver, we will attest PLGA-TPGS-NPs and PLC-PLA-TPGS-NPs have the effect of liver targeting. That has certain practical value.in the areas of new OA preparations, industrial production of the nanoparticles and clinical research. |
