Adagen,腺苷脱氨酶缺乏症的酶替代疗法,是1990年代初批准的第一个蛋白质-聚合物缀合物。在这一监管批准之后,许多聚合物药物和聚合物纳米颗粒已经进入市场作为先进或下一代聚合物为基础的治疗,而其他许多人目前已经进行了临床试验。与治疗部分缀合的聚合物提供了几个优点,比如增强药物的溶解,控释,降低免疫原性,延长循环。本综述旨在强调治疗有效的聚合物-药物缀合物(PDC)设计中的考虑因素,包括接头化学的选择。制定PDC的潜在合成策略已经随着不同类型的PDC的最新进展进行了讨论,即,聚合物-小分子量药物偶联物,聚合物-蛋白质结合物,和刺激响应性PDC,正在进行临床/临床前调查。已经解决了阻碍PDC临床转化为改善疾病状况的有效治疗方案的当前障碍和调节障碍。
Adagen, an enzyme replacement treatment for adenosine deaminase deficiency, was the first protein-polymer conjugate to be approved in early 1990 s. Post this regulatory approval, numerous polymeric drugs and polymeric nanoparticles have entered the market as advanced or next-generation polymer-based therapeutics, while many others have currently been tested clinically. The polymer conjugation to therapeutic moiety offers several advantages, like enhanced solubilization of drug, controlled release, reduced immunogenicity, and prolonged circulation. The present review intends to highlight considerations in the design of therapeutically effective polymer-drug conjugates (PDCs), including the choice of linker chemistry. The potential synthetic strategies to formulate PDCs have been discussed along with recent advancements in the different types of PDCs, i.e., polymer-small molecular weight drug conjugates, polymer-protein conjugates, and stimuli-responsive PDCs, which are under clinical/preclinical investigation. Current impediments and regulatory hurdles hindering the clinical translation of PDC into effective therapeutic regimens for the amelioration of disease conditions have been addressed.