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 ∼2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ∼3.3 ng/ml on day 1, which dropped 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 (∼25-30 ng/g from day 1-4 and ∼10-15 ng/g at 90 days), 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.
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY-40202, USA.
Shyam S
SS
Bansal
Hina
H
Kausar
Manicka V
MV
Vadhanam
Srivani
S
Ravoori
Ramesh C
RC
Gupta
D020341:Absorbable Implants; D000284:Administration, Oral; D000818:Animals; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003580:Cytochromes / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D008862:Microsomes, Liver / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D011912:Rats, Inbred ACI; D014018:Tissue Distribution / Q000187:drug effects
D003580:Cytochromes; D003692:Delayed-Action Preparations; D011108:Polymers; D003577:Cytochrome P-450 Enzyme System; C465260:Cyp3a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D005982:Glutathione Transferase; D003474:Curcumin