Drug Development through Modification of Small Molecular Drugs with Monodisperse Poly(ethylene glycol)s

Poly(ethylene glycol)s (PEGs) are the most used polymers in biomedicine, and their so-called "stealth" effects are the "gold standard" for biomaterials. However, the polydispersity in regular PEGs hampers their biomedical application, especially in modification of small molecular drugs (SMDs). To address this issue, many synthetic strategies for monodisperse PEGs (M-PEGs) have recently been developed. More importantly, M-PEGs have been successfully employed to modify SMDs, and the crucial roles of M-PEGs in PEGylated SMDs have been discovered in many cases. Herein we summarize the strategies for the synthesis of M-PEGylated SMDs, including Movantik, NKTR-181, polidocanol, propofol, and camptothecin, and the important roles of M-PEGs in optimizing the physicochemical properties, bioavailability, and therapeutic efficacy of SMDs. M-PEGylation is a convenient and effective strategy to develop novel SMDs, especially on the basis of marketed drugs. This review may shed light on the rational design and efficient synthesis of new M-PEGylated SMDs.