Title : From self-assembly to healing: Engineering ultra-small peptides into supramolecular hydrogels for controlled drug release
Abstract:
The objective of this study was to assess the suitability of novel mucoadhesive hydrogel platforms for delivering therapeutics targeting gastrointestinal (GI) disorders. To this end, we developed and characterized novel hydrogels based on self-assembling lipopeptides namely MPD02-09, created by covalently conjugating lauric acid (LA) to ultra-small peptide with the sequence Ser-Asn-Ala (SNA) and its derivatives. These were obtained by incorporating various combinations of D- and L-amino acids into the native SNA structure. LA conjugation was performed to enhance peptide stability, induce amphiphilicity, and promote hydrogel formation via self-assembly. Budesonide (BUD), an anti-inflammatory drug, commonly used for the treatment of GI disorders, was chosen as model drug to evaluate the loading capacity of these systems. Initial investigations examined how the conjugates’ chemical structures influenced key physicochemical properties relevant to drug delivery. Among these, two selected lipopeptides, MPD03 and MPD08, successfully formed hydrogels (MPD03h and MPD08h) with proper rheological properties and promising drug delivery characteristics. These include approximately 60% mucoadhesiveness, an important characteristic that allows the formulation to withstand peristaltic movements as well as the washing effect of body fluids, which reduce the percentage of drug payload available systemically, providing a certain oral viscous media suitable for intended therapeutic applications. In vitro studies demonstrated that BUD-loaded hydrogels released around 70% of the drug within 6 hours. Wound healing assays using Caco-2 and HaCaT cells showed a reduction in cell-free area to below 10%. Together, these findings indicate that MPD03h and MPD08h are suitable candidates for the delivery of BUD in the management of GI disorders.
