From self-Assembly to healing: Engineering ultra-Small peptides into supramolecular hydrogels for controlled drug release.

ABSTRACT

The aim of this study was the evaluation of suitability of novel mucoadhesive hydrogel platforms for the delivery of therapeutics useful for the management of disorders related to the gastrointestinal tract (GI). At this purpose, here we describe the preparation, the physicochemical characterization and drug delivery behaviour of novel hydrogels, based on self-assembling lipopeptides (MPD02-09), obtained by covalently conjugating lauric acid (LA) to SNA's peptide derivatives gotten by variously combining D- and L- amino acid residues. LA conjugation was aimed at improving the stability of the precursor peptides, obtaining amphiphilic structures, and triggering the hydrogels formation through the self-assembling. Budesonide (BUD), an anti-inflammatory drug, was selected as model because of its use in the treatment in GI disorders. Preliminary studies were performed to correlate the chemical structure of the conjugates with the key physicochemical properties of the materials for drug delivery. Two lipopeptides, MPD03 and MPD08, were found to form hydrogels (MPD03h and MPD08h, respectively) with characteristics suitable for drug delivery. These materials showed mucoadhesiveness of about 60 %. In vitro studies carried out with BUD loaded hydrogels showed about 70 % drug release within 6 h. Wound healing assessed in Caco-2 and HaCaT cells, showed reduction of cell-free area to values lower than 10 %. Taking together these results MPD03h and MPD08h have been shown to be excellent candidates for BUD delivery.