Quality and defined chemical composition are essential for pharmaceutical formulations. Purity requirements dictated by regulatory agencies and pharmacopoeias ensure the safety and reproducibility of all ingredients in marketed formulations. Poly(ethylene glycol) (PEG) derivatives are one of the most widely used polymeric excipients, with over 50 years of applications in medicine. Initially employed to “hide” proteins from the immune system, its use has expanded to liposomal formulations, copolymers and drug conjugates. The rise of antibody drug-conjugates has demonstrated the benefit of single-length, also known as monodisperse, PEG derivatives. In this article, we summarise the current applications of monodisperse PEG derivatives in both academic and commercial settings. With the newly available monodisperse PEG 2000 and new research on PEG 5000, we also highlight potential
areas where polydisperse PEG could be replaced with its monodisperse equivalent.
Uniformity and Defined Composition of Monodisperse PEG Polymers are inherently polydisperse, consisting of a mixture of different molecule lengths, which is a consequence of the industrial polymerisation methods.1 PEG is typically obtained via anionic ring-opening polymerisation (ROP) of ethylene oxide (EO). This method yields a mixture of PEG molecules with a Gaussian distribution of chain lengths (Figure 1). Although modern polymerisation methods have been improved with new catalysts and post-synthetic treatments to narrow the distribution, heterogeneous materials are still generated. For instance, PEG 2000 with a narrow polydispersity index (PDI) of 1.02 still contains over 25 different PEG chain lengths.2
