title: A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery.
abstract: The purpose of this study was to develop a novel featured and flexible methotrexate (MTX) formulation, in which MTX was physically entrapped and chemically conjugated in the same drug delivery system. A series of poloxamer-MTX (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through an ester bond. p-MTX conjugates could self-assemble into micelle-like structures in aqueous environment and the MTX end was in the inner-core of micelles. Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic core region to increase the total drug loading. Importantly, the resulting MTX-loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast release of the entrapped MTX (about 6-7h) followed by a sustained release of the conjugated MTX. The pharmacokinetics study showed that the mean residence time (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed MTX elimination from the bloodstream and prolonged in vivo residence time. Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p-MTX micelles might be a promising nanosized drug delivery system for the cancer therapy.
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Target Drug and Clinial Application, School of Pharmacy, Xuzhou Medical College, 209 Tongshanlu, Xuzhou 221004, China.
authors: Jin
authors: J
authors: Ren
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Zhengjie
authors: Z
authors: Fang
authors: Department of Pharmaceutics, Siping central People's Hospital, 89 Yingbinjie, Siping 136000, China.
authors: Li
authors: L
authors: Yao
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Fatima Zohra
authors: FZ
authors: Dahmani
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Lifang
authors: L
authors: Yin
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: zhoujpcpu@163.com.
authors: Jianping
authors: J
authors: Zhou
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: yaoj3@163.com.
authors: Jing
authors: J
authors: Yao
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004952:Esters / Q000737:chemistry; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D008823:Micelles; D053758:Nanoparticles; D010316:Particle Size; D020442:Poloxamer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000963:Antimetabolites; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004952:Esters; D008823:Micelles; D020442:Poloxamer; D008727:Methotrexate
keywords: Bioavailability; Biphasic release; Dicyclohexylcarbodiimide (PubChem CID: 10868); Dicyclohexylurea (PubChem CID: 4277); Dimethylaminopyridine (PubChem CID: 14284); MTX; Methanol (PubChem CID: 887); Methotrexate (PubChem CID: 24897373); Micelles; N,N-dimethylformamide (PubChem CID: 6228); N-hydroxysuccinimide (PubChem CID: 80170); Poloxamer; Poloxamer (PubChem CID: 10129990); Pyrene (PubChem CID: 31423); Theophylline (PubChem CID: 2153)