An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug

TitleAn injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug
Publication TypeJournal Article
Year of Publication2023
AuthorsOzer, I, Slezak, A, Sirohi, P, Li, X, Zakharov, N, Yao, Y, Everitt, JI, Spasojevic, I, Craig, SL, Collier, JH, Campbell, JE, D'Alessio, DA, Chilkoti, A
JournalBiomaterials
Volume294
Pagination121985
Date Published12/2023
ISSN01429612
Abstract

Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. However, the improvement in the plasma half-life of PEGylated drugs' is at an asymptote because the development of branched PEG has only had a modest impact on pharmacokinetics and pharmacodynamics. Here, we developed an injectable PEG-like conjugate that forms a subcutaneous depot for the sustained delivery of biologics. The PEG-like conjugate consists of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) conjugated to exendin, a peptide drug used in the clinic to treat type 2 diabetes. The depot-forming exendin-POEGMA conjugate showed greater efficacy than a PEG conjugate of exendin as well as Bydureon, a clinically approved sustained-release formulation of exendin. The injectable depot-forming exendin-POEGMA conjugate did not elicit an immune response against the polymer, so that it remained effective and safe for long-term management of type 2 diabetes upon chronic administration. In contrast, the PEG conjugate induced an anti-PEG immune response, leading to early clearance and loss of efficacy upon repeat dosing. The exendin-POEGMA depot also showed superior long-term efficacy compared to Bydureon. Collectively, these results suggest that an injectable POEGMA conjugate of biologic drugs that forms a drug depot under the skin, providing favorable pharmacokinetic properties and sustained efficacy while remaining non-immunogenic, offers significant advantages over other commonly used drug delivery technologies.

URLhttps://www.sciencedirect.com/science/article/pii/S0142961222006251
DOI10.1016/j.biomaterials.2022.121985
Short TitleBiomaterials