Sulistio Adrian, Reyes-Ortega Felisa, D'Souza Asha M, Ng Sarah M Y, Valade David, Quinn John F, Donohue Andrew C, Mansfeld Friederike, Blencowe Anton, Qiao Greg, Prankerd Richard, Quirk Stephen, Whittaker Michael R, Davis Thomas P, Tait Russell J
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, 381 Royal Pde Parkville, VIC, 3052, Australia.
J Mater Chem B. 2017 Aug 21;5(31):6221-6226. doi: 10.1039/c7tb01518f. Epub 2017 Jul 31.
A facile synthesis method of polymer diclofenac conjugates (PDCs) based on biocompatible polyurethane chemistry that provides a high drug loading and offers a high degree of control over diclofenac (DCF) release kinetics is described. DCF incorporating monomer was reacted with ethyl-l-lysine diisocyanate (ELDI) and different amounts of polyethylene glycol (PEG) in a one-step synthesis to yield polymers with pendent diclofenac distributed along the backbone. By adjusting the co-monomers feed ratio, the drug loading could be tailored accordingly to give DCF loading of up to 38 w/w%. The release rate could also be controlled easily by changing the amount of PEG in the backbone. Above 10 w/w% of PEG, the in vitro DCF release studies in physiological conditions showed an apparent zero-order profile without an initial burst effect for up to 120 days. The PDCs described may be suitable for long-term intra-articular (IA) delivery for the treatment of osteoarthritis (OA).
描述了一种基于生物相容性聚氨酯化学的聚合物双氯芬酸缀合物（PDCs）的简便合成方法，该方法具有高载药量，并能高度控制双氯芬酸（DCF）的释放动力学。将含DCF的单体与乙基-L-赖氨酸二异氰酸酯（ELDI）和不同量的聚乙二醇（PEG）进行一步合成反应，生成沿主链分布有侧链双氯芬酸的聚合物。通过调整共聚单体的进料比，可以相应地调整载药量，使DCF载量高达38 w/w%。通过改变主链中PEG的量，也可以轻松控制释放速率。当PEG含量高于10 w/w%时，在生理条件下的体外DCF释放研究显示，在长达120天的时间内呈现明显的零级释放曲线，且无初始突释效应。所述的PDCs可能适用于骨关节炎（OA）治疗的长期关节内（IA）给药。
