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

Abstract

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.

Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery

“…Its performance extending the elimination half-life of a drug has become the gold standard for nanoscale materials 6 . So far, more than 20 PEGylated liposomes or RNA have been approved by the Food and Drug Administration of the United States, such as Doxil ® and Macugen ® for clinical application, which plays an extremely vital role in treating cancer and neovascular age-related macular degeneration, respectively 7 . Compared with linear PEG, other shapes of PEG were rarely used.…”

Anti-Survival Effect of SI306 and Its Derivatives on Human Glioblastoma Cells

“…Indeed, a careful analysis of the literature highlighted that introducing a poly(ethylene glycol) (PEG) chain can successfully modulate drug delivery [ 17 ]. As different studies pointed out that the activity of many small molecules is improved by PEGylation [ 18 ], we synthesized compound 3 ( Figure 1 ), which bears two ethylene glycol units on the carbamate moiety. We chose this short PEG chain driven by the rationale to balance a feasible synthesis with the chance to afford a compound characterized by improved ADME (Absorption, Distribution, Metabolism, Excretion) properties.…”

Journey of Poly(ethylene Glycol) in Living Cells

“…), and a lot of candidates are still in clinical/preclinical trails [e.g., polyglutamate–paclitaxel (Xyotax), N -(2-hydroxypropyl)­methacrylamide (HPMA) copolymer–doxorubicin–galactosamine poly­(ethylene glycol) (PEG)–camptothecin, and dextran–doxorubicin] (clinical status from: ). Among the strategies of polymer modification, PEGylation, which is proposed to dramatically improve pharmacological and physiological properties of the conjugated drug by reducing cytotoxicity and immunogenicity, prolonging blood circulation time, diminishing degradation by the enzymes, and altering bio-distribution profile, has a preponderant use in pharmaceutical industry since 1970s. − Currently, 26 PEGylated products have been approved by FDA for clinical use, proving the applicability and effectiveness of PEGylation technology. , …”

“…4−9 Currently, 26 PEGylated products have been approved by FDA for clinical use, proving the applicability and effectiveness of PEGylation technology. 10,11 With the wide application of PEG and PEGylation, it is necessary to interpret the interaction between PEG and biological systems. Meanwhile, because many complex networks of events occurred in living cells have been deciphered, the ability to target therapeutics inside cells is becoming more and more important and current drug design strategies are focused on specific intracellular organelle delivery.…”