title: Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles.
abstract: Curcumin (CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability. To progress the bioavailability and water solubility of CUR, we synthesized five series of mono methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by H NMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxicity of void CUR, mPEG-PCL and CUR/mPEG-PCL micelles was compared to each other by performing MTT assay of the treated MCF-7 and 4T1 cell line. Study of the in vivo pharmacokinetics of the CUR-loaded micelles was also carried out on selected copolymers in comparison with CUR solution formulations. The results showed that the zeta potential of CUR-loaded micelles was about -11.5mV and the average size was 81.0nm. CUR was encapsulated into mPEG-PCL micelles with loading capacity of 20.65±0.015% and entrapment efficiency of 89.32±0.34%. The plasma AUC (0-t), t1/2and Cmaxof CUR micelles were increased by 52.8, 4.63 and 7.51-fold compared to the CUR solution, respectively. In vivo results showed that multiple injections of CUR-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of CUR. These results suggested that mPEG-PCL micelles would be a potential carrier for CUR.
authors.affiliation: Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Kheiri Manjili
authors.affiliation: School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Ghasemi
authors.affiliation: School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Hojjat
authors.initials: H
authors.lastname: Malvandi
authors.affiliation: School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Mir Sajjad
authors.initials: MS
authors.lastname: Mousavi
authors.affiliation: School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Attari
authors.affiliation: Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address: danafar@zums.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Danafar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Cancer therapy; Copolymer; Curcumin; Micelles; Pharmacokinetics