Human serum albumin (HSA) has been shown to be an ideal protein for nanoparticle preparation. These are usually prepared by using cross linker agents such as glutaraldehyde (GAD). Liquid lipid nanocapsules (LLN) constitute a new generation of nanoparticles more biocompatible and versatile for oral delivery of lipophylic drugs. The first barrier that an orally administered formulation must cross is the gastrointestinal tract. Hence, it is crucial to address the impact of gastrointestinal digestion on these structures in order to achieve an optimal formulation. This study evaluates the effect of gastric digestion on HSA emulsions structured with GAD as a model substrate for the preparation of LLN. This is done by SDS-PAGE, emulsion microstructure, and interfacial tension techniques. Our results demonstrate that the cross- linking procedure with GAD strongly inhibits pepsin digestion by formation of inter- and/or intramolecular covalent bonds between substrate amino acids. Emulsification of HSA also protects from gastric digestion probably by the orientation of the HSA molecule, which exposes the majority of pepsin cleaving sites preferably to the hydrophobic part of the oil-water interface. In this emulsified HSA, cross-linking with GAD at the interface promotes structural modifications on the HSA interfacial layer, restricting the access of pepsin to cleavage sites. We identify interfacial aspects underlying enzymatic hydrolysis of the protein. Assuring that HSA-GAD structures resist passage through the gastric compartment is crucial is important towards the rational design of oral delivery systems and the first step to get the complete digestion profile.
Keywords: Cross linker; Digestion; Emulsion; Interfacial tension; Nanocapsules; Oral delivery.
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