title: Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin.
abstract: To precisely manipulate the intracellular delivery of pleiotropic curcumin, this work reports two types of acid-responsive polymer-curcumin conjugates with different structures. One or two amphiphilic poly(ethylene glycol)-co-poly(lactic acid) (PEG-PLA) copolymer(s) were linked to curcumin via pH-liable hydrazone, producing a linear or phospholipid-like conjugate, respectively. Both conjugates efficiently self-assembled into micellar nanocarriers with enhanced stability in contrast to the paralleling PEG-PLA micelles. In comparison to the micelles assembled by phospholipid-like conjugates, the linear conjugate micelles exhibited similar size, doubled loading dose, higher release rate, and hence enhanced cellular uptake and cytotoxicity at the cost of increased critical micelle concentration. This work highlighted the importance of precise tuning of polymer-drug conjugate architecture in determining the pharmaceutical properties and thus delivery efficiency of the corresponding conjugate micelles.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, Tianjin, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, Tianjin, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, Tianjin, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, Tianjin, China. Electronic address: zhaoyj@tju.edu.cn.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D003474:Curcumin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Curcumin; Drug delivery; Micelle; Polymeric conjugate; Self-assembly; Stimuli-responsive