Curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of paclitaxel upon administration in nanoemulsion formulation.
The aim of this study was to evaluate the effect of curcumin (CUR) in oral bioavailability and therapeutic efficacy of paclitaxel (PTX) administered in nanoemulsion to SKOV3 tumor-bearing nu/nu mice. Oral administration of the mice with CUR at 50 mg/kg for 3 consecutive days resulted in a down regulation of intestinal P-glycoprotein (Pgp) and cytochrome P450 3A2 (CYP3A2) protein levels. PTX, a Pgp and CYP3A2 substrate, was administered orally at 20 mg/kg in solution or nanoemulsion either as single agent or upon pretreatment with CUR at 50 mg/kg in tumor-bearing mice. Plasma AUC(0-∞) of PTX administered in nanoemulsion to CUR pretreated mice showed 4.1-fold increase relative to controls. Similarly, relative PTX bioavailability was increased by 5.2-fold, resulting in a 3.2-fold higher PTX accumulation in the tumor tissue. PTX administered in nanoemulsion to CUR pretreated mice also showed significantly enhanced anti-tumor activity. Preliminary safety evaluation showed that CUR + PTX combination did not induce any acute toxicity as measured by body weight changes, blood cell counts, liver enzyme levels, and liver histopathology. The results of this study suggest that combination of PTX and CUR, administered in nanoemulsions, could improve oral bioavailability and therapeutic efficacy in ovarian adenocarcinoma.
Ganta
Srinivas
S
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, USA.
Devalapally
Harikrishna
H
Amiji
Mansoor
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004655:Emulsions / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D004791:Enzyme Inhibitors; D051544:Cytochrome P-450 CYP3A; D003474:Curcumin; D017239:Paclitaxel