Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells
Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells
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DOI：
10.1016/j.jcis.2010.05.022
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发表时间：
2010-11-01
影响因子：
9.9
通讯作者：
Chauhan, Subhash C.
中科院分区：
文献类型：
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作者：
Yallapu, Murali Mohan;Gupta, Brij K.;Chauhan, Subhash C.
姜黄素是一种天然多酚类化合物，具有良好的抗癌和化疗活性。尽管I期临床试验表明姜黄素即使在高剂量下也是一种安全的药物，但生物利用度差和次优的药代动力学在很大程度上缓和了其在临床前和临床模型中的抗癌活性。为了提高其在癌症治疗中的适用性，我们在聚（乙烯醇）和聚（L-赖氨酸）稳定剂的存在下，使用纳米沉淀技术，将姜黄素封装在聚（乳酸-共-乙交酯）（PLGA）（可生物降解聚合物）纳米颗粒中。这些姜黄素纳米制剂的特征在于粒径，zeta电位，药物包封，药物相容性和药物释放。姜黄素以高度分散的状态存在于纳米粒的PLGA核中，并表现出良好的固-固相容性。优化的姜黄素纳米制剂（nano-CUR 6）已经证明，与游离姜黄素相比，在顺铂抗性A2780 CP卵巢癌细胞和转移性MDA-MB-231乳腺癌细胞中进行的细胞摄取分别增加了2倍和6倍。在这些细胞中，与游离姜黄素相比，nano-CUR 6在细胞增殖和克隆形成测定中显示出改善的抗癌潜力。这种作用与纳米CUR 6制剂诱导的增强的细胞凋亡相关。在本文中，我们还显示了我们的PLGA-NP制剂的抗体缀合相容性。该研究的结果表明，姜黄素的治疗功效可以通过这样的PLGA纳米颗粒制剂来增强，并且此外，通过将抗癌抗体偶联至纳米颗粒，使得姜黄素的肿瘤特异性靶向递送成为可行的。(C)2010年爱思唯尔公司All rights reserved.
Curcumin, a natural polyphenolic compound, has shown promising chemopreventive and chemotherapeutic activities in cancer. Although phase I clinical trials have shown curcumin as a safe drug even at high doses, poor bioavailability and suboptimal pharmacokinetics largely moderated its anti-cancer activity in pre-clinical and clinical models. To improve its applicability in cancer therapy, we encapsulated curcumin in poly(lactic-co-glycolide) (PLGA) (biodegradable polymer) nanoparticles, in the presence of poly(vinyl alcohol) and poly(L-lysine) stabilizers, using a nano-precipitation technique. These curcumin nano-formulations were characterized for particle size, zeta potential, drug encapsulation, drug compatibility and drug release. Encapsulated curcumin existed in a highly dispersed state in the PLGA core of the nanoparticles and exhibited good solid-solid compatibility. An optimized curcumin nano-formulation (nano-CUR6) has demonstrated two and sixfold increases in the cellular uptake performed in cisplatin resistant A2780CP ovarian and metastatic MDA-MB-231 breast cancer cells, respectively, compared to free curcumin. In these cells, nano-CUR6 has shown an improved anti-cancer potential in cell proliferation and clonogenic assays compared to free curcumin. This effect was correlated with enhanced apoptosis induced by the nano-CUR6 formulation. Herein, we have also shown antibody conjugation compatibility of our PLGA-NP formulation. Results of this study suggest that therapeutic efficacy of curcumin may be enhanced by such PLGA nanoparticle formulations, and furthermore tumor specific targeted delivery of curcumin is made feasible by coupling of anti-cancer antibody to the NPs. (C) 2010 Elsevier Inc. All rights reserved.