Enable Therapeutic Peptides Delivery with Enhanced Stability and Bioavailability Through Advanced Characterization

Title: Enable therapeutic peptides delivery with enhanced stability and bioavailability through advanced characterization
Abstract: The global market for peptide therapeutics from both parenteral and oral delivery is expanding across various therapeutic domains, underscoring the potential of peptides in addressing unmet medical needs. For parenteral peptide formulation, peptides commonly aggregate into amyloid fibrils, which are highly undesirable due to the reductions in bioavailability and bioactivity resulting from the stability and insolubility of fibrils, as well as potentially increased toxicity and immunogenicity. Understanding the impact of peptide structure and formulation conditions on the peptide aggregation and stability through advanced characterization can aid building SAR and designing formulation with robust stability. In addition, in recent years, the quest for non-invasive, patient-friendly delivery methods has led to intensive research into alternative strategies, with oral delivery standing out as a highly desirable option. Efforts to circumvent these barriers have seen a mix of innovative chemistry and the adoption of intestinal permeation enhancers (PEs), which aim to increase membrane permeability and, consequently, oral bioavailability. This highlights the critical need for an in-depth exploration of the mechanisms through which PEs navigate the complex physiological barriers inherent to oral delivery systems. Despite these advancements, the bioavailability of peptides in the presence of PEs remains low, typically around 2% in both preclinical and clinical settings. Unraveling these mechanisms is crucial for the rational design and optimization of PEs, focusing on enhancing their structural properties to potentially improve bioavailability. In this presentation, we will share two the case studies (1) investigate the pH dependence of peptide oligomerization and explore the potential structural impacts of peptide lipidation on this process through biophysical and advanced analytical characterizations and (2) employs advanced spectroscopic tools to investigate how two common PEs interact with hydrated DMPC liposomes, measuring enhancements in membrane fluidity across interfacial and transmembrane regions.