Poly(pro-curcumin) Materials Exhibit Dual Release Rates and Prolonged Antioxidant Activity as Thin Films and Self-Assembled Particles
Poly(pro-curcumin) Materials Exhibit Dual Release Rates and Prolonged Antioxidant Activity as Thin Films and Self-Assembled Particles
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DOI：
10.1021/acs.biomac.2c01135
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发表时间：
2023-01-09
影响因子：
6.2
通讯作者：
Palermo, Edmund F.
中科院分区：
文献类型：
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作者：
Chen, Ruiwen;Funnell, Jessica L.;Palermo, Edmund F.
姜黄素是一种天然多酚，具有显著的抗氧化和抗炎活性，但其生理不稳定性在一定程度上限制了其临床应用。在这里，我们报道了姜黄素衍生的聚酯的合成，这些聚酯在水解降解时释放姜黄素，以改善姜黄素在生理条件下的稳定性和溶解性。姜黄素在二十二烷基氯和聚乙二醇一锅缩聚反应中被引入到聚合物主链中。其热学和力学性质、表面润湿性、自组装行为和药物释放动力学都敏感地依赖于姜黄素在这些统计共聚物中的摩尔百分比。姜黄素的释放是由聚合物主链上的酚酸酯的水解触发的，用聚乙二醇化的姜黄素模型化合物证实了这一点，该化合物代表了聚合物中的一个假定的重复单元。姜黄素的释放速率受聚合物的亲水性控制。根据共聚物中姜黄素含量的不同，同一聚合物可以实现爆释(2天)和缓释(>；8周)。该材料可以在体外至少8周的时间内抑制自由基，保护原代神经元免受氧化应激的影响。此外，根据溶剂型浇注条件的不同，这些共聚材料可以加工成薄膜和自组装颗粒。最后，我们展望这些材料可能具有神经组织工程应用的潜力，其中抗氧化剂的释放可以减轻神经损伤后的氧化应激和炎症反应。
Curcumin is a natural polyphenol that exhibits remarkable antioxidant and anti-inflammatory activities; however, its clinical application is limited in part by its physiological instability. Here, we report the synthesis of curcumin-derived polyesters that release curcumin upon hydrolytic degradation to improve curcumin stability and solubility in physiological conditions. Curcumin was incorporated in the polymer backbone by a one-pot condensation polymerization in the presence of sebacoyl chloride and polyethylene glycol (PEG, Mn = 1 kDa). The thermal and mechanical properties, surface wettability, self-assembly behavior, and drug-release kinetics all depend sensitively on the mole percentage of curcumin incorporated in these statistical copolymers. Curcumin release was triggered by the hydrolysis of phenolic esters on the polymer backbone, which was confirmed using a PEGylated curcumin model compound, which represented a putative repeating unit within the polymer. The release rate of curcumin was controlled by the hydrophilicity of the polymers. Burst release (2 days) and extended release (>8 weeks) can be achieved from the same polymer depending on curcumin content in the copolymer. The materials can quench free radicals for at least 8 weeks and protect primary neurons from oxidative stress in vitro. Further, these copolymer materials could be processed into both thin films and self-assembled particles, depending on the solvent-based casting conditions. Finally, we envision that these materials may have potential for neural tissue engineering application, where antioxidant release can mitigate oxidative stress and the inflammatory response following neural injury.