IMX Talks - Gastric stable double Pickering emulsions as oral co-delivery systems for hydrophilic drugs and hydrophobic permeation enhancers

Oral administration is the most facile, cheap, and compliant drug delivery route, but bioavailability is often impaired by the harsh gastric environment and limited intestinal permeation, particularly in case of peptide drugs. To that end, we have developed a novel gastric stable water-in-oil-in water double emulsion toward simultaneous administration of hydrophilic drugs and hydrophobic permeation enhancers, respectively. Exploiting a two-step emulsification and a Pickering stabilization mechanism using solid nanoparticles, we were able to obtain double emulsions that remain stable over several months and can efficiently encapsulate hydrophilic compounds in the internal water phase. The double emulsions remain stable under simulated in vitro gastric conditions and show limited leakage of the encapsulated compound. The oil phase further allows the incorporation of a hydrophobic permeation enhancer (C10) at physiologically relevant concentrations. Studies on differentiated Caco-2 cell model intestinal monolayers confirmed that double emulsions containing C10 were able to temporarily reduce monolayer integrity and facilitate permeation of peptide-sized model drugs. We conclude that Pickering double emulsions are a potential gastric stable oral delivery system for the co-delivery of hydrophilic and hydrophobic excipients such as peptide drugs and permeation enhancers.