Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; National Science Research Council (CONICET), Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Colloids Surf B Biointerfaces. 2014 Jan 1;113:43-50. doi: 10.1016/j.colsurfb.2013.07.036. Epub 2013 Sep 5.
The purpose of this work was to develop Cremophor(®) EL-free nanoparticles (NPs) loaded with Paclitaxel (PTX) in order to improve the drug i.v. pharmacokinetic profile and to evaluate its activity against commercially available formulations such as Taxol(®) and Abraxane(®). PTX-loaded poly(ε-caprolactone)-alpha tocopheryl polyethylene glycol 1000 succinate (PCL-TPGS) NPs were prepared using three different techniques: (i) by nanoprecipitation (NPr-method), (ii) by emulsion-solvent evaporation homogenized with an Ultra-Turrax(®) (UT-method) and (iii) by emulsion-solvent evaporation homogenized with an ultrasonicator (US-method). The NPs prepared by US-method showed the smallest size and the highest drug content. The NPs exhibited a slow and continuous release of PTX. The in vitro anti-tumoral activity was assessed using two human breast cancer cell lines (MCF-7 and MDA-MB-231) with the WTS assay. Cytotoxicity studies with both cell lines showed that PTX-loaded PCL-TPGS NPs exhibited better anti-cancer activity compared to PTX solution and the commercial formulation Abraxane(®) at different concentrations. Importantly, in the case of triple negative MDA-MB-231 breast cancer cells, the IC50 value for PTX-loaded PCL-TPGS NPs was 7.8 times lower than Abraxane(®). Finally, in vivo studies demonstrated that PTX-loaded PCL-TPGS NPs exhibited longer systemic circulation time and slower plasma elimination rate than Taxol(®) and Abraxane(®). Therefore, the novel NPs investigated might be an alternative nanotechnological platform for PTX delivery system in cancer chemotherapy.
这项工作的目的是开发不含 Cremophor(®) EL 的紫杉醇（PTX）载纳米粒（NPs），以改善药物的静脉内药代动力学特征，并评估其对市售制剂如 Taxol(®)和 Abraxane(®)的活性。采用三种不同技术制备载紫杉醇的聚（ε-己内酯）-α-生育酚聚乙二醇 1000 琥珀酸酯（PCL-TPGS）NPs：（i）通过纳米沉淀（NPr 法），（ii）通过乳液-溶剂蒸发并用 Ultra-Turrax(®)（UT 法）匀化，和（iii）通过乳液-溶剂蒸发并用超声处理器（US 法）匀化。US 法制备的 NPs 粒径最小，载药量最高。NPs 表现出缓慢而持续的 PTX 释放。采用 WST 测定法，使用两种人乳腺癌细胞系（MCF-7 和 MDA-MB-231）评估 NPs 的体外抗肿瘤活性。用两种细胞系进行的细胞毒性研究表明，与 PTX 溶液和市售制剂 Abraxane(®)相比，载 PTX 的 PCL-TPGS NPs 在不同浓度下表现出更好的抗癌活性。重要的是，在三阴性 MDA-MB-231 乳腺癌细胞中，载 PTX 的 PCL-TPGS NPs 的 IC50 值比 Abraxane(®)低 7.8 倍。最后，体内研究表明，载 PTX 的 PCL-TPGS NPs 的系统循环时间长，血浆消除率慢，优于 Taxol(®)和 Abraxane(®)。因此，所研究的新型 NPs 可能是癌症化疗中 PTX 递药系统的一种替代纳米技术平台。
