title: Preparation of intravenous injection nanoformulation via co-assemble between cholesterylated gemcitabine and cholesterylated mPEG: enhanced cellular uptake and intracellular drug controlled release.
abstract: The objective of this study was to prepare the CHS-mPEG/CHS-dFdC nanoformulation could be administrated through intravenous injection in nude mice. Particularly, CHS-mPEG was selected to co-assemble with CHS-dFdC to improve the prodrug concentration and enhance the stability of nanoformulation. The nanoformulation could be prepared by codissolution-coprecipitation. All of the nanoformulations kept stable in PBS at 4 °C or simulative human plasma at 37 °C. As molar ratios of CHS-mPEG1900/CHS-dFdC increased from 0.1/1 to 2/1, the weight concentration of CHS-dFdC increased from 2.5 to 15 mg/mL. It was found the optimal CHS-mPEG1900/CHS-dFdC nanoformulation displayed controlled drug release in simulative lysosome condition. The amount of released dFdC reached up to 90% within 10 h. It also exhibited enhanced cellular uptake ability, 7-folds higher than that of dFdC during 2.5 h incubation. And it showed superior cytotoxicity resulted from the enhanced cellular uptake ability on BxPC-3 cells.
authors.affiliation: a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering , East China Normal University , Shanghai , PR China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering , East China Normal University , Shanghai , PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering , East China Normal University , Shanghai , PR China.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering , East China Normal University , Shanghai , PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering , East China Normal University , Shanghai , PR China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Yu
authors.affiliation: b Department of Radiology and Nuclear Medicine , Changzheng Hospital, The Second Millitary Medical University , Shanghai , PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: b Department of Radiology and Nuclear Medicine , Changzheng Hospital, The Second Millitary Medical University , Shanghai , PR China.
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: c School of Chemistry and Chemical Engineering , Southwest University , Chongqing , PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics*; D002460:Cell Line; D003692:Delayed-Action Preparations; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000737:chemistry*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D003841:Deoxycytidine; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D000093542:Gemcitabine
keywords: CHS-dFdC; CHS-mPEG; enhanced cellular uptake; intracellular drug controlled release; nanoformulation