Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as stabilizer.
BACKGROUND
CUR is a promising drug candidate based on its good bioactivity, but use of CUR is potentially restricted because of its poor solubility and bioavailability.


OBJECTIVE
The aim of this study was to prepare an aqueous formulation of curcumin nanosuspension (CUR-NS) to improve its solubility and change its in vivo behavior.


METHODS
CUR-NS was prepared by high-pressure homogenization method. Drug state in CUR-NS was evaluated by powder X-ray diffraction. Pharmacokinetics and biodistribution of CUR-NS after intravenous administration in rabbits and mice were studied.


RESULTS
The solubility and dissolution of CUR in the form of CUR-NS were significantly higher than those of crude CUR. X-ray crystallography diffraction indicated that the crystalline state of CUR in nanosuspension was preserved. Pharmacokinetics and biodistribution results of CUR-NS after intravenous administration in rabbits and mice showed that CUR-NS presented a markedly different pharmacokinetic property as compared to the CUR solution. AUC(0-infinity) of CUR-NS (700.43 +/- 281.53 microg/mL, min) in plasma was approximately 3.8-fold greater than CUR solution (145.42 +/- 9.29 microg/mL min), and the mean residence time (194.57 +/- 32.18 versus 15.88 +/- 3.56 minutes) was 11.2-fold longer.


CONCLUSIONS
Nanosuspension could serve as a promising intravenous drug-delivery system for curcumin.
Gao
Yan
Y
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, China.
Li
Zhonggang
Z
Sun
Min
M
Li
Houli
H
Guo
Chenyu
C
Cui
Jing
J
Li
Aiguo
A
Cao
Fengliang
F
Xi
Yanwei
Y
Lou
Hongxiang
H
Zhai
Guangxi
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004355:Drug Stability; D005079:Excipients; D007262:Infusions, Intravenous; D051379:Mice; D053758:Nanoparticles; D054118:Nanospheres / Q000032:analysis* / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols; D011208:Powders; D011817:Rabbits; D012995:Solubility; D013535:Suspensions; D014018:Tissue Distribution; D014810:Vitamin E / Q000031:analogs & derivatives*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005079:Excipients; D011208:Powders; D013535:Suspensions; D014810:Vitamin E; D011092:Polyethylene Glycols; D003474:Curcumin; C014225:tocophersolan