title: Acetal-linked polymeric prodrug micelles for enhanced curcumin delivery.
abstract: On-demand curcumin delivery via stimuli-responsive micellar nanocarriers holds promise for addressing its solubility and stability problem. Polymer-curcumin prodrug conjugate micelle is one of such nanosystems. The diversity of linker and conjugation chemistry enabled the generation and optimization of different curcumin micelles with tunable stimuli-responsiveness and delivery efficiency. The aim of the current work was to generate and assess acetal-linked polymeric micelles to enrich the pH-responsive curcumin delivery platforms. Curcumin was slightly modified prior to conjugating to amphiphilic methoxy poly(ethylene glycol)-poly(lactic acid) (mPEG-PLA) copolymer via an acetal bond, whereas an ester bond-linked conjugate was used as the control. The acetal-containing micelles showed a hydrodynamic diameter of 91.1 ± 2.9(nm) and the accompanying core size of 63.5 ± 7.1 (nm) with a zeta potential of -10.9 ± 0.7(mV). Both control and pH-labile micelles displayed similar critical micelle concentration at 1.6 μM. The acetal-containing nanocarriers exhibited a pH-dependent drug release behavior, which was faster at lower pH values. The cytotoxicity study in HepG2 cells revealed a significantly lower IC50 at 51.7 ± 9.0(μM) for acetal-linked micelles in contrast to the control at 103.0 ± 17.8(μM), but the polymer residue showed no cytotoxicity upon drug release. The acetal-linked micellar nanocarrier could be a useful addition to the spectrum of currently available stimuli-responsive curcumin nano-formulations.
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Yunlan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Fan
authors.affiliation: Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, People's Republic of China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: wangzheng2006@tju.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: zhaoyj@tju.edu.cn.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000080:Acetals / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000080:Acetals; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011355:Prodrugs; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Conjugate; Curcumin; Drug delivery; Micelle; Stimuli-responsive