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

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 similar to 2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was similar to 3.3 ng/ml on day 1, which dropped to similar to 0.2 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 +/- 7.3 vs 2.7 +/- 0.8 ng/g) and were still significant even after 90 days (7.7 +/- 3.8 vs 2.2 +/- 0.8 ng/g). Although curcumin levels were similar in liver from both the routes (similar to 25-30 ng/g from day 1-4 and similar to 10-15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at similar to 28-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. (C) 2012 Elsevier B.V. All rights reserved.