Sustained release of GLP-1 analog from γ-PGA-PAE copolymers for management of type 2 diabetes

GLP-1 has been clinically exploited for treating type 2 diabetes, while its short circulation half-life requires multiple daily injections to maintain effective glycemic control, thus limiting its widespread application. Here we developed a drug delivery system based on self-assembling polymer-amino acid conjugates (γ-PGA-PAE) to provide sustained release of GLP-1 analog (DLG3312). The DLG3312 loaded γ-PGA based nanoparticles (DLG3312@NPs) exhibited a spherical shape with a good monodispersity under transmission electron microscope (TEM) observation. The DLG3312 encapsulation was optimized, and the loading efficiency was as high as 78.4 ± 2.2 %. The transformation of DLG3312@NPs to network structures was observed upon treatment with the fresh serum, resulting in a sustained drug release. The in vivo long-term hypoglycemic assays indicated that DLG3312@NPs significantly reduced blood glucose and glycosylated hemoglobin level. Furthermore, DLG3312@NPs extended the efficacy of DLG3312, leading to a decrease in the dosing schedule that from once a day to once every other day. This approach combined the molecular and materials engineering strategies that offered a unique solution to maximize the availability of anti-diabetic drug and minimize its burdens to type 2 diabetic patients.