biostudies-literatureOzer ICenter for AIDS Research, University of WashingtonNIDDK NIH HHSCenter for AIDS Research, Duke UniversityArmy Research OfficeNational Institutes of HealthSchool of Medicine, Duke University121985https://www.ebi.ac.uk/biostudies/studies/S-EPMC10918641biostudies-literatureUnknown294Many 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-releaBiomaterialsAn injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.PMC10918641R01DK124276W911NF-20-2-0182R01 DK124276Sirohi PCollier JHCampbell JED'Alessio DASpasojevic IChilkoti AZakharov NEveritt JILi XYao YOzer ISlezak ACraig SLfalseAn injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.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-relea2023-01-01T00:00:00Z2023 Mar2025-04-04T12:58:26.732Z2025-04-04T12:58:26.732ZS-EPMC109186413663082610.1016/j.biomaterials.2022.121985