title: Particle size effect of curcumin nanosuspensions on cytotoxicity, cellular internalization, in vivo pharmacokinetics and biodistribution.
abstract: This study aimed to investigate the particle size effect on bioactivity, cellular internalization and bioavailability of curcumin (CUR) nanosuspension (CUR-NS). CUR-NSs of different particle sizes were prepared by two different anti-solvent precipitation methods. CUR-NS with the smallest size showed similar in vitro anticancer activity and bioavailability to the CUR solution, whereas nanosuspensions of larger particle sizes displayed higher in vitro cellular internalization and cytotoxicity, as well as higher in vivo AUC and slower clearance rate after i.v. administration in rats. CUR solution and different sized CUR-NSs reached the highest concentrations in the lung, followed by liver and spleen while the lowest concentration was observed in the brain after i.v. administration in mice. Specifically, CUR-NS of 70nm accumulated more in the brain, whereas CUR-NS of 200nm accrued more in liver and spleen. CUR-NS of 20nm displayed no significant biodistribution difference compared with CUR solution in all tissues.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR, China; Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, China.
authors.forename: Xiao Qing
authors.initials: XQ
authors.lastname: Miao
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, China.
authors.forename: Sing Fung
authors.initials: SF
authors.lastname: Chow
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR, China.
authors.forename: Wen Jin
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Yan
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Liao
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, China.
authors.forename: Albert Hee-Lum
authors.initials: AH
authors.lastname: Chow
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR, China. Electronic address: yzheng@umac.mo.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000032:analysis; D009369:Neoplasms / Q000188:drug therapy; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin
keywords: Anticancer activity; Biodistribution; Curcumin nanosuspensions; Multi-inlet vortex mixer; Particle size; Pharmacokinetics