Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA.
Drug Deliv Transl Res. 2011 Aug;1(4):332-41. doi: 10.1007/s13346-011-0028-0.
Curcumin, an anti-oxidant, anti-inflammatory, and anti-neoplastic agent, exhibited limited oral efficacy due to its poor bioavailability. To overcome this limitation, polymeric implants for continuous systemic delivery of curcumin were developed and tested for their safety and biocompatibility. Two 2-cm polycaprolactone implants containing polyethylene glycol and 20% (w/w) curcumin were grafted subcutaneously at the back of the Augustus Copenhagen Irish rats. Rats were euthanized and blood was analyzed for various hematological parameters; biochemical markers of liver/kidney function and local tissues were analyzed for local inflammatory reactions. Curcumin implants exhibited biphasic release kinetics with ∼3.6 + 0.8, 5.8 ± 1.1, 13.1 ± 2.1, 21.8 ± 0.3, 38.1 ± 0.6, and 47.2 ± 1.6 mg cumulative curcumin being released from both the implants after 1, 4, 12, 25, and 90 days. No significant differences in various hematological parameters (like white blood cells, red blood cells, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin), liver enzymes (like aspartate transaminase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, amylase, or lipase), or biochemical parameters of kidney function (like blood urea nitrogen, creatinine, Ca(2+), Na(+), and Cl(-) levels) were observed at any of these time points. However, a significant increase in serum phosphorus levels was observed at all the time points in sham implants as well as in curcumin diet and implant groups. Local implantation site showed foreign body granulomatous reaction with influx of histiocytes and occasional multi-nucleated giant cells with sham implants and was minimal around the curcumin implants. These polymeric implants were found to have little or no systemic toxicity with an acute reaction at local site which was reduced significantly by curcumin implants.
姜黄素是一种抗氧化、抗炎和抗肿瘤的药物，但由于其生物利用度差，口服疗效有限。为了克服这一限制，开发了用于姜黄素持续全身递送的聚合物植入物，并对其安全性和生物相容性进行了测试。将含有聚乙二醇和 20%（w/w）姜黄素的两个 2 厘米长的聚己内酯植入物皮下植入奥古斯都哥本哈根爱尔兰大鼠的背部。处死大鼠，分析血液的各种血液学参数；分析生化标志物肝/肾功能和局部组织的局部炎症反应。姜黄素植入物表现出两相释放动力学，在 1、4、12、25 和 90 天后，从两个植入物中分别释放出约 3.6±0.8、5.8±1.1、13.1±2.1、21.8±0.3、38.1±0.6 和 47.2±1.6 毫克累积姜黄素。在任何时间点，各种血液学参数（如白细胞、红细胞、血红蛋白、平均红细胞体积和平均红细胞血红蛋白）、肝酶（如天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转肽酶、淀粉酶或脂肪酶）或肾功能的生化参数（如血尿素氮、肌酐、Ca(2+)、Na(+)和 Cl(-)水平）均无显著差异。然而，在假植入物以及姜黄素饮食和植入物组中，所有时间点的血清磷水平均显著升高。在假植入物和姜黄素植入物周围，局部植入部位显示异物性肉芽肿反应，伴有组织细胞浸润和偶尔的多核巨细胞。这些聚合物植入物被发现具有很少或没有全身毒性，局部部位的急性反应被姜黄素植入物显著减轻。
