Injectable sustained release microparticles of curcumin: a new concept for cancer chemoprevention.
Injectable sustained release microparticles of curcumin: a new concept for cancer chemoprevention.
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DOI：
10.1158/0008-5472.can-09-4362
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发表时间：
2010-06-01
期刊：
影响因子：
11.2
通讯作者：
Panyam J
中科院分区：
文献类型：
--
作者：
Shahani K;Swaminathan SK;Freeman D;Blum A;Ma L;Panyam J
口服生物利用度差限制了姜黄素和其他膳食多酚在预防和治疗癌症中的使用。微创策略，可以提供有效和持续的组织浓度的这些药物将是非常有价值的工具，在打击癌症。本研究的目的是研究使用姜黄素的可注射缓释微粒制剂作为乳腺癌化学预防的新方法。采用生物可降解的生物相容性高分子材料聚（D，L-丙交酯-乙交酯）（PLGA）制备姜黄素微粒。当皮下注射小鼠时，单剂量的微粒可使血液和其他组织中的姜黄素水平维持近一个月。肺和脑中的姜黄素水平是乳腺癌转移的常见部位，比血液中的高10-30倍。此外，与其他对照相比，姜黄素微粒在携带MDA-MB-231异种移植物的裸鼠中显示出显著的抗癌功效。反复全身注射姜黄素对抑制肿瘤生长无效。用姜黄素微粒治疗导致VEGF表达减少和肿瘤微血管发育不良，表明对肿瘤血管生成有显著影响。这些结果表明，使用聚合物微粒持续递送化学预防剂如姜黄素是癌症化学预防和治疗的一种有前途的新方法。
Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA), was used to fabricate curcumin microparticles. When injected subcutaneously in mice, a single dose of microparticles sustained curcumin levels in the blood and other tissues for nearly a month. Curcumin levels in the lungs and brain, frequent sites of breast cancer metastases, were 10-30-fold higher than that in the blood. Further, curcumin microparticles showed marked anticancer efficacy in nude mice bearing MDA-MB-231 xenografts compared to other controls. Repeated systemic injections of curcumin were not effective in inhibiting tumor growth. Treatment with curcumin microparticles resulted in diminished VEGF expression and poorly developed tumor microvessels, indicating a significant effect on tumor angiogenesis. These results suggest that sustained delivery of chemopreventives such as curcumin using polymeric microparticles is a promising new approach to cancer chemoprevention and therapy.