Encapsulation and release of As pidasept peptides in polysaccharide formulation for oral application

•The antimicrobial peptide Aspidasept (Pep19–2.5) acts anti-inflammatory with high affinity against bacterial toxins such as lipopolysaccharide (LPS) and lipoprotein (LP).•Polysaccharide:peptide formulations for oral applications provide sufficient stability in the gastrointenstinal tract, in particular in the stomach.•These formulations still guarantee the anti-inflammatory property.•Alginate-peptide complexes were shown to fulfill the criteria of stability and anti-inflammatory activity.•In conclusion: a peptide formulation for oral application is available which should be useful for the fight against infections of the gastro-intestinal tract such as IBD (inflammatory bowel diseases) and Morbus Crohn. Due to the increase in bacterial resistance to common antibiotics and the lack of newly approved drugs, antimicrobial peptides (AMP) have been shown to be an alternative to combat infections caused by drug-resistant organisms. In particular, synthetic anti-lipopolysaccharide peptides (SALP) with the lead structure Aspidasept (Pep19–2.5) display a high anti-inflammatory activity in vitro and in vivo systems of endotoxemia and bacteremia. This was found not only when SALP were applied systemically (i.e. against sepsis), but also in topical therapies aimed at treating wound infections. A further important application involves combating common pathologies of the gastrointestinal tract, such as chronic infections of the small intestine and the colon (e.g., Crohn's disease). For the necessary oral application, the active pharmaceutical ingredient (API), Aspidasept®, must be encapsulated to ensure its protection against the low pH and the hydrolytic enzymes of the gastrointestinal tract. Here, the encapsulation of Aspidasept in polysaccharide matrices, essentially alginate and pectin, was systematically investigated with a variety of physico-chemical techniques. Specifically, we characterized key features of the nanoparticles such as their sizes and size distributions, as well as their stability in different environments mimicking digestive fluids. Finally, we studied the release of the drug from the polysaccharide matrices and the ability of nanoparticles to neutralize endotoxemia in vitro. We showed that our lead formulations exert an optimum inhibitory activity on immune cells stimulated by lipopolysaccharide. Encapsulated Pep19–2.5:alginate complexes at a molar ratio 100:1 as seen by atomic force microscopy at two magnifications: The particles are composed of