Controlled systemic delivery by polymeric implants enhances tissue and plasma curcumin levels compared with oral administration

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• 作者：Shyam S. Bansal^a ; ^b ; ^c ; Hina Kausar^b ; Manicka V. Vadhanam^b ; Srivani Ravoori^b ; Ramesh C. Gupta^a ; ^b ; ^{rcgupta@louisville.edu}
• 关键词：PCL-121 ; poly (蔚-caprolactone) of 121 ; 000 molecular weight ; PEG 8K ; polyethylene glycol (molecular weight 8000) ; CYP1A1 ; cytochrome P450 1A1 ; CYP3A4 ; cytochrome P450 3A4 ; GSTM ; glutathione S-transferase (渭) ; PBS ; phosphate-buffered-saline ; BCS ; bovine c
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2012
• 期刊代码：16_09396411
• 类别：pha
• 出版时间：April, 2012
• 卷：80
• 期：3
• 页码：571-577
• 文件大小：457 K

摘要

Curcumin possesses potent anti-inflammatory and anti-proliferative activities but with poor biopharmaceutical attributes. To overcome these limitations, curcumin implants were developed and tissue (plasma, brain and liver) curcumin concentrations were measured in female ACI rats for 3 months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with 鈭?-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was 鈭?.3 ng/ml on day 1, which dropped to 鈭?.2 ng/ml after 3 months, whereas only 0.2-0.3 ng/ml concentration was observed from 4-12 days with diet and was undetected subsequently. Almost 10-fold higher curcumin levels were observed in brain on day 1 from implants compared with diet (30.1 卤 7.3 vs 2.7 卤 0.8 ng/g) and were still significant even after 90 days (7.7 卤 3.8 vs 2.2 卤 0.8 ng/g). Although curcumin levels were similar in liver from both the routes (鈭?5-30 ng/g from day 1-4 and 鈭?0-15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at 鈭?8-fold lower doses at 90 days. Curcumin implants provided much higher plasma and tissue concentrations and are a viable alternative for delivery of curcumin to various organs like brain.