title: Preparation, characterization, and in vitro drug release behavior of glutathione-sensitive long-circulation micelles based on polyethylene glycol prodrug.
abstract: In this paper, a kind of glutathione-sensitive polymeric micelles was prepared through assembling in aqueous solution of an amphiphilic polymeric prodrug which was synthesized by linkage of 6-mercaptopurine (6-MP) and polyethylene glycol monomethyl ether using propiolic acid as a connecting arm. The glutathione (GSH)-sensitive strategy is based on a Michael addition-elimination reaction, that is the amphiphilic polymeric prodrug which contains α, β-unsaturated carbonyl group acts as a Michael acceptor to receive the attack of nucleophile - glutathione, and undergoes elimination reaction to release the original drug. Transmission electron microscope observation showed that the polymeric micelles (PMs) had a spherical-like morphology with a mean diameter of 28 ± 3.2 nm. The dynamic light scattering investigation data exhibited that the size and distribution changes of PMs are negligible after being placed for 15 days. In vitro drug release study indicated that only less than 13% of 6-MP was released from the micelles under GSH stimulation at micromolar level, while 34.5, 53.7, and 77.8% accumulative release rates were achieved under GSH stimulation at millimolar level (1, 2 and 10 mM), respectively. The cell inhibition rate of PM solution against HL-60 cells carried out by MTT method reached 85%. The cellular uptake and the intracellular drug release of PMs in HL-60 cells were observed through determining the intracellular 6-MP content by UV-vis spectrophotometer. In vitro macrophage uptake study showed a low phagocytosis rate, indicating the long-circulation ability of the PMs.
authors.affiliation: a Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , Wuhan , P.R. China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Shi
authors.affiliation: a Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , Wuhan , P.R. China.
authors.forename: Kaikai
authors.initials: K
authors.lastname: Ding
authors.affiliation: a Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , Wuhan , P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: a Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , Wuhan , P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , Wuhan , P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zeng
authors.affiliation: a Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , Wuhan , P.R. China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yin
authors.affiliation: a Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , Wuhan , P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D015122:Mercaptopurine / Q000737:chemistry; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011355:Prodrugs; D014867:Water; D011092:Polyethylene Glycols; D015122:Mercaptopurine; D005978:Glutathione
keywords: 6-mercaptopurine; Polyethylene glycol monomethyl ether; glutathione sensitive; long-circulation ability; prodrug-based polymeric micelle