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

• Published in: European journal of pharmaceutics and biopharmaceutics 2012-04, Vol.80 (3), p.571-577
• Main Authors: Bansal, Shyam S., Kausar, Hina, Vadhanam, Manicka V., Ravoori, Srivani, Gupta, Ramesh C.
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Administration, Oral; Animals; Bioavailability; Biological and medical sciences; Chemoprevention; Controlled release; Curcumin; Curcumin - administration & dosage; Curcumin - pharmacokinetics; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Cytochromes - drug effects; Cytochromes - metabolism; Delayed-Action Preparations; Drug Delivery Systems - methods; Female; General pharmacology; Glutathione Transferase - genetics; Implants; Kinetics; Liver - drug effects; Liver - metabolism; Medical sciences; Metabolic Detoxication, Phase I - genetics; Metabolic Detoxication, Phase II - genetics; Microsomes, Liver - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymers - administration & dosage; Polymers - pharmacokinetics; Rats; Rats, Inbred ACI; Tissue curcumin levels; Tissue Distribution - drug effects
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.12.009

Schematic of observed curcumin distribution to various tissues from polymeric implants as compared to dietary 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 3months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with ∼2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ∼3.3ng/ml on day 1, which dropped to ∼0.2ng/ml after 3months, whereas only 0.2–0.3ng/ml concentration was observed from 4–12days 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±0.8ng/g) and were still significant even after 90days (7.7±3.8 vs 2.2±0.8ng/g). Although curcumin levels were similar in liver from both the routes (∼25–30ng/g from day 1–4 and ∼10–15ng/g at 90days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at ∼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.