Electrohydrodynamic fabrication of core-shell PLGA nanoparticles with controlled release of cisplatin for enhanced cancer treatment.
Electrohydrodynamic fabrication of core-shell PLGA nanoparticles with controlled release of cisplatin for enhanced cancer treatment.
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DOI：
10.2147/ijn.s134833
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发表时间：
2017
影响因子：
8
通讯作者：
Knowles JC
中科院分区：
文献类型：
--
作者：
Reardon PJ;Parhizkar M;Harker AH;Browning RJ;Vassileva V;Stride E;Pedley RB;Edirisinghe M;Knowles JC
通过靶向给药提高毒性化疗药物如顺铂(CDDP)的临床疗效是癌症治疗研究的一个关键领域。本研究采用电流体雾化(EHDA)技术，成功制备了载顺铂的聚乳酸-乙醇酸共聚纳米粒(PLGA)。通过改变构型来控制顺铂在颗粒中的分布，获得了高包封率(70%)的药物。以核-壳(CS)或基质(均匀)结构制备NPS。结果表明，CS纳米粒在两种制剂中具有最持久的释放，在最初的“爆裂”后表现出较慢的线性释放和较长的持续时间。用不同的动力学模型对实验数据进行了拟合，证实了微粒构型对药物体外释放速率的影响。这表明药物的释放过程是一个简单的扩散机制。与游离药物(EC50=9微米)和均匀分布的CDDP纳米粒(EC50=7.6微米)相比，CS纳米粒可有效地内化到癌细胞的内溶酶体隔间，并显示出更高的细胞毒效(半数最大反应药物浓度[EC50]达到6.2微米)。因此，这些实验表明，设计PLGA纳米粒的结构可以用来控制剂量和释放特性，以改善临床化疗治疗。
Increasing the clinical efficacy of toxic chemotherapy drugs such as cisplatin (CDDP), via targeted drug delivery, is a key area of research in cancer treatment. In this study, CDDP-loaded poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) were successfully prepared using electrohydrodynamic atomization (EHDA). The configuration was varied to control the distribution of CDDP within the particles, and high encapsulation efficiency (>70%) of the drug was achieved. NPs were produced with either a core–shell (CS) or a matrix (uniform) structure. It was shown that CS NPs had the most sustained release of the 2 formulations, demonstrating a slower linear release post initial “burst” and longer duration. The role of particle architecture on the rate of drug release in vitro was confirmed by fitting the experimental data with various kinetic models. This indicated that the release process was a simple diffusion mechanism. The CS NPs were effectively internalized into the endolysosomal compartments of cancer cells and demonstrated an increased cytotoxic efficacy (concentration of a drug that gives half maximal response [EC50] reaching 6.2 µM) compared to free drug (EC50 =9 µM) and uniform CDDP-distributed NPs (EC50 =7.6 µM) in vitro. Thus, these experiments indicate that engineering the structure of PLGA NPs can be exploited to control both the dosage and the release characteristics for improved clinical chemotherapy treatment.