Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy.
Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy.
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DOI：
10.1186/1477-3155-5-3
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发表时间：
2007-04-17
影响因子：
10.2
通讯作者：
Maitra A
中科院分区：
文献类型：
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作者：
Bisht S;Feldmann G;Soni S;Ravi R;Karikar C;Maitra A;Maitra A
姜黄素是从姜黄（Curcuma longa）根茎中提取的黄色多酚，具有有效的抗癌特性，如在大量的人类癌细胞系和动物致癌模型中所证明的。然而，这种相对有效的药剂在癌症和其他疾病中的广泛临床应用由于水溶性差而受到限制，因此全身生物利用度最小。基于纳米颗粒的药物递送方法具有使疏水剂如姜黄素可分散在水性介质中的潜力，从而避免了溶解度差的缺陷。我们利用N-异丙基丙烯酰胺（NIPAAM）与N-乙烯基-2-吡咯烷酮（VP）和聚（乙二醇）单丙烯酸酯（PEG-A）的交联和无规共聚物的胶束聚集体合成了姜黄素的聚合物纳米颗粒包封制剂-纳米姜黄素。通过动态激光光散射和透射电子显微镜对聚合物纳米颗粒的物理化学表征证实了在50 nm范围内的窄尺寸分布。与游离姜黄素不同，纳米姜黄素容易分散在水性介质中。通过软琼脂中的细胞活力和克隆形成试验评估，纳米姜黄素对一组人胰腺癌细胞系的体外治疗效果与游离姜黄素相当。此外，纳米姜黄素对胰腺癌细胞的作用机制与游离姜黄素的作用机制相似，包括诱导细胞凋亡、阻断核因子κ B（NFκB）激活以及下调多种促炎细胞因子（IL-6、IL-8和TNFα）的稳态水平。纳米姜黄素提供了一个机会，以扩大这种有效的药物的临床剧目，使现成的水分散体。利用nanocurcumin的未来研究在癌症和其他可能受益于姜黄素作用的疾病的临床前体内模型中是必要的。
Curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa), has potent anti-cancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis models. Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility. We have synthesized polymeric nanoparticle encapsulated formulation of curcumin – nanocurcumin – utilizing the micellar aggregates of cross-linked and random copolymers of N-isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone (VP) and poly(ethyleneglycol)monoacrylate (PEG-A). Physico-chemical characterization of the polymeric nanoparticles by dynamic laser light scattering and transmission electron microscopy confirms a narrow size distribution in the 50 nm range. Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media. Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free curcumin against a panel of human pancreatic cancer cell lines, as assessed by cell viability and clonogenicity assays in soft agar. Further, nanocurcumin's mechanisms of action on pancreatic cancer cells mirror that of free curcumin, including induction of cellular apoptosis, blockade of nuclear factor kappa B (NFκB) activation, and downregulation of steady state levels of multiple pro-inflammatory cytokines (IL-6, IL-8, and TNFα). Nanocurcumin provides an opportunity to expand the clinical repertoire of this efficacious agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit from the effects of curcumin.