Murphy Jennifer N, Kobti Joy-Lynn, Dao Michelle, Wear Darcy, Okoko Michael, Pandey Siyaram, Vukotic V Nicholas
Department of Chemistry and Biochemistry, University of Windsor 401 Sunset Avenue Windsor ON N9B 3P4 Canada
Department of Chemistry, University of Guelph 50 Stone Rd E Guelph ON N1G 2W1 Canada.
Chem Sci. 2024 Apr 11;15(19):7041-7050. doi: 10.1039/d4sc00732h. eCollection 2024 May 15.
Developing tunable materials which exhibit sustained drug release is a considerable challenge. Herein, we report the concept of Therapeutic Coordination Polymers (TCPs); non-porous coordination polymers constructed from biocompatible components which demonstrate tunable zero-order drug release kinetics upon degradation of metal-ligand bonds. TCPs were constructed from three principal components: (i) a cationic metal center (M = Mg, Mn, Zn, or Cu); (ii) an anionic drug (Diclofenac); and (iii) an alkyl bis-imidazole organic ligand which behaves as a "linker" between metal centers. Most drug-release materials, such as amorphous polymer dispersions, or metal-organic frameworks rely on a diffusion-based mechanism for drug release, but the degradation-controlled release of drugs from non-porous one-periodic coordination polymers has been largely unexplored. TCPs described herein exhibit a high wt% of pharmaceutical (>62%), tailorable zero-order drug release rate kinetics which span over three orders of magnitude, and stimuli-responsive drug release behavior making them well suited for extended drug-release applications.
开发具有持续药物释放性能的可调谐材料是一项巨大的挑战。在此,我们报告了治疗性配位聚合物(TCPs)的概念;由生物相容性成分构建的无孔配位聚合物,在金属-配体键降解时表现出可调谐的零级药物释放动力学。TCPs由三种主要成分构成:(i)阳离子金属中心(M = 镁、锰、锌或铜);(ii)阴离子药物(双氯芬酸);(iii)烷基双咪唑有机配体,其作为金属中心之间的“连接体”。大多数药物释放材料,如无定形聚合物分散体或金属有机框架,依赖基于扩散的药物释放机制,但从无孔单周期配位聚合物中通过降解控制药物释放的情况在很大程度上尚未得到探索。本文所述的TCPs表现出高重量百分比的药物(>62%)、可定制的零级药物释放速率动力学,其跨越三个数量级,以及刺激响应性药物释放行为,使其非常适合长效药物释放应用。