Proteolysis-Resistant Self-Assembled ω-Amino Acid Dipeptide-Based Biocompatible Hydrogels as Drug Delivery Vehicle

In this report we demonstrate the excellent hydrogelating ability of two Fluorenylmethoxycarbonyl (Fmoc) protected dipeptides, Fmoc-Xaa-Phe-OH (Xaa, Gaba, Hydrogelator I; Xaa, Ava, Hydrogelator II; Gaba=gamma -aminobutyric acid; Ava= delta-Amino Valeric acid) with omega-amino acids exhibiting conformational flexibility. Since Proteolysis is the disadvantage for peptide-based therapeutic agents, our design includes dipeptides known to show resistance towards proteolysis. The gelation property of the hydrogels were characterized by various analysis. It was concluded that the hydrogels were non cytotoxic in four completely different cell lines, which indicates its biocompatibility. These biomaterials were used to stabilize nanoparticles (HNPs) using the concept of self-assembly, utilizing weak interactions rather than extreme conditions as seen in other polymers. These hydrogelators have shown good entrapment efficiency and release kinetics of the model drug curcumin from the hydrogel matrix. Our investigation reveals that hydrogelator II has an enhanced release profile due to the presence of methylene groups in the peptide backbone. This hypothesis is also supported by our computational studies.Thus our research holds future promise for using these biomaterials as vehicles for drug delivery.