Traditional approaches to achieve sustained delivery of pharmaceutical peptides\ntraditionally use co-excipients (e.g., microspheres and hydrogels). Here, we investigate the release of\nan amyloidogenic glucagon analogue (3474) from an aggregated state and the influence of surfactants\non this process. The formulation of peptide 3474 in dodecyl maltoside (DDM), rhamnolipid (RL), and\nsophorolipid (SL) led to faster fibrillation. When the aggregates were subjected to multiple cycles\nof release by repeated resuspension in fresh buffer, the kinetics of the release of soluble peptide\n3474 from different surfactant aggregates all followed a simple exponential decay fit, with half-lives\nof 5-18 min and relatively constant levels of release in each cycle. However, different amounts\nof peptide are released from different aggregates, ranging from 0.015 mg/mL (3475-buffer) up to\n0.03 mg/mL (3474-DDM), with 3474-buffer and 3474-RL in between. In addition to higher release\nlevels, 3474-DDM aggregates showed a different amyloid FTIR structure, compared to 3474-RL\nand 3474-SL aggregates and a faster rate of degradation by proteinase K. This demonstrates that\nthe stability of organized peptide aggregates can be modulated to achieve differences in release of\nsoluble peptides, thus coupling aggregate polymorphism to differential release profiles. We achieved\naggregate polymorphism by the addition of different surfactants, but polymorphism may also be\nreached through other approaches, including different excipients as well as changes in pH and\nsalinity, providing a versatile handle to control release profiles.
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