Figure 1.
PNP hydrogels for the prolonged delivery of GLP-1 RAs
(A) From literature reports it is clear that once-weekly dosing frequency does not significantly improve patient compliance compared with a once-daily dosing frequency.7
(B) Localized depots form in the subcutaneous space immediately after subcutaneous injection, providing a tunable platform for sustained release of GLP-1-RA compounds.
(C) Clinical data showing the release profile of current GLP-1 treatments, where the black dotted line represents repeated weekly injections that patients take every week for 4 months to reach therapeutic concentrations of GLP-1 RA. In contrast, the blue line represents the target delivery profile of a single PNP hydrogel depot injection that sustains release of GLP-1 RA for 120 days. Current state-of-the-art strategies require daily or weekly subcutaneous injections with significant ramp-up time to achieve therapeutic concentrations. The red dotted line indicates the therapeutic threshold.
(D) Semaglutide and liraglutide are once-weekly and once-daily, respectively, GLP-1 RA therapies that were investigated in this study.
(E) PNP hydrogels prepared by mixing hydrophobically modified HPMC with PEG-PLA nanoparticles enable facile encapsulation of GLP-1-receptor agonists with 100% efficiency.