论文部分内容阅读
目的以聚乙二醇-聚己内酯(polyethylene glycol-b-poly caprolactone,m PEG-b-PCL)为聚合物,硬脂酸单双甘油酯(geleol mono and diglycerides Nf,GMD)为固体脂质,制备拉洛他赛共聚物脂质杂合纳米粒(larotaxel-solid lipid core-contained polymeric nanoparticles,LTX-cSLNs)并评价其性能。方法采用透析法制备LTX-cSLNs,以粒径、多分散系数(polydispersity index,PDI)、载药量(drug loading content,wDL)和包封率(entrapment efficiency,wEE)为评价指标,采用单一因素法筛选最优处方工艺。采用高效液相色谱法测定LTX-cSLNs的wDL和wEE,激光散射粒度测定仪测定粒径和电位,采用透射电镜观察形态,采用差示扫描量热法测定GMD在纳米粒内核的存在形式。同时以不含GMD的纳米粒(larotaxel-solid lipid core-uncontained polymeric nanoparticles,LTX-u SLNs)作为对照,比较两种制剂在临界聚集质量浓度(critical aggregation concentration,ρCAC)以及体内外性能的差异。结果 LTXcSLNs帯有脂质内核,平均粒径为56.8 nm,zeta电位为-13.56 m V,wDL为12.9%,wEE为81.46%,ρCAC为0.126 mg·L~(-1)。LTX-cSLNs能够延缓累积释放量达12%,药时曲线下面积(AUC0-t)提高近16.7%。结论 LTX-cSLNs具有高载药量、高稳定性以及良好的体内外性能。
OBJECTIVE: To synthesize polyethylene glycol-b-poly caprolactone (m PEG-b-PCL) as polymer and geleol mono and diglycerides Nf (GMD) The larotaxel-solid lipid core-contained polymeric nanoparticles (LTX-cSLNs) were prepared and their properties were evaluated. Methods LTX-cSLNs were prepared by dialysis method. The particle size, polydispersity index (PDI), drug loading content (wDL) and entrapment efficiency (wEE) Law screening the best prescription process. The wDL and wEE of LTX-cSLNs were determined by high performance liquid chromatography (HPLC). The particle size and potential of LTX-cSLNs were measured by laser scattering particle size analyzer. The morphologies of the nanoparticles were observed by transmission electron microscopy and the existence of GMD in the nanoparticle core was determined by differential scanning calorimetry. At the same time, the differences of critical aggregation concentration (ρACA) and in vitro and in vivo performance of the two preparations were compared using GMD-free nanoparticles (LTX-u SLNs) as control. Results The LTXcSLNs had a lipid core with an average particle size of 56.8 nm, zeta potential of -13.56 mV, wDL of 12.9%, wEE of 81.46% and ρCAC of 0.126 mg · L -1. LTX-cSLNs delayed cumulative release by 12% and increased the area under the curve (AUC0-t) by nearly 16.7%. Conclusion LTX-cSLNs have high drug loading, high stability and good in vitro and in vivo performance.