High drug payload curcumin nanosuspensions stabilized by mPEG-DSPE and SPC: in vitro and in vivo evaluation.
BACKGROUND
Curcumin (CUR) is a promising drug candidate based on its broad bioactivities and good antitumor effect, but the application of CUR is potentially restricted because of its poor solubility and bioavailability.


OBJECTIVE
This study aims at developing a simple and effective drug delivery system for CUR to enhance its solubility and bioavailability thus to improve its antitumor efficacy.


METHODS
Curcumin nanosuspensions (CUR-NSps) were prepared by precipitation-ultrasonication method using mPEG2000-DSPE and soybean lecithin as a combined stabilizer.


RESULTS
CUR-NSps with a high drug payload of 67.07% were successfully prepared. The resultant CUR-NSps had a mean particle size of 186.33 ± 2.73 nm with a zeta potential of -19.00 ± 1.31 mV. In vitro cytotoxicity assay showed that CUR-NSps exhibited enhanced cytotoxicity compared to CUR solution. The pharmacokinetics results demonstrated that CUR-NSps exhibited a significantly greater AUC0-24and prolonged MRT compared to CUR injections after intravenous administration. In the biodistribution study, CUR-NSps demonstrated enhanced biodistribution compared with CUR injections in liver, spleen, kidney, brain, and tumor. The CUR-NSps also showed improved antitumor therapeutic efficacy over the injections (70.34% versus 40.03%, p < 0.01).


CONCLUSIONS
These results suggest that CUR-NSps might represent a promising drug formulation for intravenous administration of CUR for the treatment of cancer.
a Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
Jingyi
J
Hong
a Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.|b School of Pharmacy, Heilongjiang University of Chinese Medicine , Harbin , China , and.
Yingying
Y
Liu
a Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.|b School of Pharmacy, Heilongjiang University of Chinese Medicine , Harbin , China , and.
Yao
Y
Xiao
a Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
Xiaofeng
X
Yang
c Life Science and Environmental Science Center, Harbin University of Commerce , Harbin , China.
Wenjing
W
Su
c Life Science and Environmental Science Center, Harbin University of Commerce , Harbin , China.
Mingzhu
M
Zhang
a Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
Yonghong
Y
Liao
b School of Pharmacy, Heilongjiang University of Chinese Medicine , Harbin , China , and.
Haixue
H
Kuang
a Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
Xiangtao
X
Wang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D054709:Lecithins / Q000737:chemistry* / Q000302:isolation & purification; D008297:Male; D008813:Mice, Inbred ICR; D050997:Nanomedicine; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013025:Glycine max / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D014961:X-Ray Diffraction; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D054709:Lecithins; C099730:N-carbamylmethoxypoly(ethylene glycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D003474:Curcumin
Curcumin; antitumor efficacy; biodistribution; high drug payload; nanosuspensions; pharmacokinetics