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Colloids Surf B Biointerfaces. 2016 Apr 1;140:11-18. doi: 10.1016/j.colsurfb.2015.12.025. Epub 2015 Dec 18.

Acetal-linked polymeric prodrug micelles for enhanced curcumin delivery.

Author information

1
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.
2
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.
3
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.
4
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.

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.

KEYWORDS:

Conjugate; Curcumin; Drug delivery; Micelle; Stimuli-responsive

PMID:
26731193
DOI:
10.1016/j.colsurfb.2015.12.025
[Indexed for MEDLINE]

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