Bernabeu Ezequiel, Gonzalez Lorena, Legaspi Maria J, Moretton Marcela A, Chiappetta Diego A
J Nanosci Nanotechnol. 2016 Jan;16(1):160-70. doi: 10.1166/jnn.2016.10739.
Nanomedicines have become an attractive platform for the development of novel drug delivery systems in cancer chemotherapy. Polymeric nanoparticles (NPs) represent one of the best well-investigated nanosized carriers for delivery of antineoplastic compounds. The "Pegylation strategy" of drug delivery systems has been used in order to improve carrier biodistribution, however, some nanosized systems with PEG on their surface have exhibited poorly-cellular drug internalization. In this context, the purpose of the present study was to compare in vitro performance of two paclitaxel (PTX)-loaded NPs systems based on two biocompatible copolymers of alpha tocopheryl polyethylene glycol 1000 succinate-block-poly(ε-caprolactone) (TPGS-b-PCL) and methoxyPEG- block-poly(ε-caprolactone) (mPEG-b-PCL) in terms of citotoxicity and PTX cellular uptake. Fur- thermore, TPGS-b-PCL NPs were also copared with the commercially available PTX nano-sized formulation Abraxane®. Both TPGS-b-PCL and mPEG-b-PCL derivates were synthesized by ring opening polymerization of ε-caprolactone employing microwaved radiation. NPs were obtained by a solvent evaporation technique where the PTX content was determined by reverse-phase HPLC. The resulting NPs had an average size between 200 and 300 nm with a narrow size distribution. Also both NPs systems showed a spherical shape. The in vitro PTX release profile from the NPs was characterized employing the dialysis membrane method where all drug-loaded formulations showed a sustained and slow release of PTX. Finally, in vitro assays demonstrated that PTX-loaded TPGS- b-PCL exhibited a significant higher antitumor activity than PTX-loaded mPEG-b-PCL NPs and Abraxane® against an estrogen-dependent (MCF-7) and an estrogen independent (MDA-MB-231) breast cancer cells lines. Furthermore TPGS-b-PCL NPs showed a significant increase on PTX cellular uptake, for both breast cell lines, in comparison with mPEG-b-PCL NPs and Abraxane®. Overall findings confirmed that NPs based on TPGS-b-PCL as biomaterial demonstrated a better in vitro performance than NPs with PEG, representing an attractive alternative for the development of novel nanosized carriers for anticancer therapy.
纳米药物已成为癌症化疗中新型药物递送系统开发的一个有吸引力的平台。聚合物纳米颗粒（NPs）是研究最充分的用于递送抗肿瘤化合物的纳米级载体之一。为了改善载体的生物分布，药物递送系统采用了“聚乙二醇化策略”，然而，一些表面带有聚乙二醇的纳米级系统表现出较差的细胞药物内化能力。在此背景下，本研究的目的是比较基于两种生物相容性共聚物——α-生育酚聚乙二醇1000琥珀酸酯-嵌段-聚（ε-己内酯）（TPGS-b-PCL）和甲氧基聚乙二醇-嵌段-聚（ε-己内酯）（mPEG-b-PCL）的两种载紫杉醇（PTX）纳米颗粒系统在细胞毒性和PTX细胞摄取方面的体外性能。此外，还将TPGS-b-PCL纳米颗粒与市售的PTX纳米制剂Abraxane®进行了比较。TPGS-b-PCL和mPEG-b-PCL衍生物均通过ε-己内酯的开环聚合反应并采用微波辐射合成。通过溶剂蒸发技术获得纳米颗粒，其中PTX含量通过反相高效液相色谱法测定。所得纳米颗粒的平均尺寸在200至300nm之间，尺寸分布狭窄。两种纳米颗粒系统均呈球形。采用透析膜法对纳米颗粒的体外PTX释放曲线进行了表征，所有载药制剂均显示PTX呈持续缓慢释放。最后，体外试验表明，载PTX的TPGS-b-PCL对雌激素依赖性（MCF-7）和雌激素非依赖性（MDA-MB-231）乳腺癌细胞系的抗肿瘤活性明显高于载PTX的mPEG-b-PCL纳米颗粒和Abraxane®。此外，与mPEG-b-PCL纳米颗粒和Abraxane®相比，TPGS-b-PCL纳米颗粒在两种乳腺癌细胞系中的PTX细胞摄取均显著增加。总体研究结果证实，以TPGS-b-PCL为生物材料的纳米颗粒在体外表现优于含聚乙二醇的纳米颗粒，是开发新型抗癌治疗纳米级载体的一个有吸引力的选择。
