Development of Thermosensitive Injectable Depot Platform for GLP-1 Peptides using Methylene Blue as a Model Hydrophilic Compound

This study aimed to develop and optimize a thermosensitive, injectable, in-situ gel depot platform for the preliminary evaluation of hydrophilic peptide delivery. Methylene blue (MB), a model hydrophilic, UV-visible molecule was utilized to monitor release dynamics relevant to glucagon-like peptide-1 (GLP-1) analogues. MB offers the advantages of low cost, chemical stability, and facile UV-visible quantification, providing an analytically tractable approach to evaluating release dynamics within the thermosensitive matrix. Poloxamer 407 (P407) was used to prepare thermoresponsive gels through the cold procedure. Formulation variables influencing gelation temperature and initial drug release were optimized using a Box–Behnken design (BBD). Diffusion-controlled release from the hydrated gel matrix was demonstrated by Formulation F6 out of fifteen, which showed a sol–gel transition temperature of 33.2 ± 0.3 °C and an initial release of 74.8 ± 2.3% within two hours. It was found that the optimized formulation had a suitable pH, thermogelling behavior, syringeability and quick in-situ depot formation under ex vivo conditions. Although the system is not a replica of commercial long-acting GLP-1 depots, it creates a rational and thermosensitive injectable platform of screening formulations prior to incorporation of enzymatically labile GLP-1 peptide analogues and subsequent in vivo evaluation.