Document Detail


Curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of paclitaxel upon administration in nanoemulsion formulation.
MedLine Citation:
PMID:  20845461     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Srinivas Ganta; Harikrishna Devalapally; Mansoor Amiji
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  99     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4630-41     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc. and the American Pharmacists Association
Affiliation:
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy*
Animals
Antineoplastic Agents, Phytogenic / administration & dosage,  pharmacokinetics*,  pharmacology,  therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / administration & dosage,  pharmacokinetics,  pharmacology,  therapeutic use
Biological Availability
Curcumin / administration & dosage,  pharmacology*
Cytochrome P-450 CYP3A / metabolism
Emulsions / chemistry
Enzyme Inhibitors / administration & dosage,  pharmacology*
Female
Humans
Mice
Ovarian Neoplasms / drug therapy*
P-Glycoprotein / metabolism
Paclitaxel / administration & dosage,  pharmacokinetics*,  pharmacology,  therapeutic use*
Grant Support
ID/Acronym/Agency:
R01-CA119617/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Emulsions; 0/Enzyme Inhibitors; 0/P-Glycoprotein; 33069-62-4/Paclitaxel; 458-37-7/Curcumin; EC 1.14.14.1/Cytochrome P-450 CYP3A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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