Currently, most drugs are directly administered into patients orally or systemically, without any specific formulation, via parenteral routes. Therefore, to get the desired therapeutic effect, high doses are required due to substantial biodegradation of the drug prior to interaction with the biological target. These high doses can however also result in the appearance of adverse effects. To overcome the need of repeated high dose administration, hydrogels have been reported as suitable controlled drug-delivery systems. More specifically, peptide hydrogels loaded with active ingredients can liquefy during injection (shear thinning behavior), followed by quick hydrogel reformation once injected. These systems present several advantages such as the protection of the drug against the enzymatic degradation by encapsulation in the hydrogel network, while maintaining the therapeutic plasma drug concentration over a long period via diffusion from the hydrogel or by degradation of the network.[1] Consequently, lower dosage and frequency of administration are possible and result in an improvement of the drug efficacy while reducing the risk of side effects. Due to their biocompatibility, their low toxicity and their physically crosslinked properties, peptide-based hydrogels represent an important class of injectable hydrogels suitable to be used as matrices for controlled and slow drug release.
In this work, a new family of hydrogel-forming peptides was designed starting from the short, tunable and amphipathic hexapeptide hydrogelator H-Phe-Glu-Phe-Gln-Phe-Lys-OH. This peptide showed interesting results in terms of gelation and in vitro drug release profile.[2] To potentially increase the enzymatic stability of the newly designed peptide hydrogelators, containing all-D-amino acid analogues were prepared as well. All hydrogels were characterized at the macroscopic and microscopic level by rheology, cryogenic transmission electron microscopy (TEM) and negative staining TEM analysis. In order to study their eventual therapeutic potential, the hydrogels have been used for entrapment and sustained release of opioid drugs. The in vitro drug release properties and hydrogel toxicity (cell viability experiments) were also determined. Based on the best physicochemical, mechanical, and noncytotoxic properties, selected hydrogels were investigated for in vivo release of opioids. Opioid administration by subcutaneous injection and subsequent testing in the tail-flick assay (acute pain model), showed sustained antinociceptive effects over longer periods of times, as compared to drug injections in saline solutions.