The bioavailability, release, and stability of pharmaceuticals under physicochemical conditions is the major cause of drug candidates failing during their clinical trials. Therefore, extensive efforts have been invested in the development of novel drug delivery systems that are able to transport drugs to a desired site and improve bioavailability. Hydrogels, and peptide hydrogels in particular, have been extensively investigated due to their excellent biocompatibility and biodegradability properties. However, peptide hydrogels often have weak mechanical strength, which limits their therapeutic efficacy. Therefore, a number of methods for improving their rheological properties have been established. This review will cover the broad area of drug delivery, focusing on the recent developments in this research field. We will discuss the variety of different types of nanocarrier drug delivery systems and then, more specifically, the significance and perspectives of peptide-based hydrogels. In particular, the interplay of intermolecular forces that govern the self-assembly of peptide hydrogels, progress made in understanding the distinct morphologies of hydrogels, and applications of non-canonical amino acids in hydrogel design will be discussed in more detail.

Bioavailability, release and stability of pharmaceuticals under physicochemical conditions is the major cause of drug candidates failing during their clinical trials. Therefore, extensive efforts have been invested in the development of novel drug delivery systems able to transport drugs to a desired site and to improve the bioavailability. Hydrogels, and peptide hydrogels in particular, have been extensively investigated due to their excellent biocompatibility and biodegradability properties. However, peptide hydrogels often have weak mechanical strength, which limits their therapeutic efficacy. Therefore, a number of methods in improving their rheological properties have been established. This review will cover the broad area of drug delivery focusing on the recent developments in this research field. We will discuss the variety of different types of nanocarrier drug delivery systems, and then, more specifically, the significance and perspectives of peptide-based hydrogels. In particular, the interplay of intermolecular forces that govern the self-assembly of peptide hydrogels, progress made in understanding the distinct morphologies of hydrogels, and applications of non-canonical amino acids in hydrogel design will be discussed in more detail.

We present a convenient and efficient approach for synthesizing lysine homologues via the Hofmann rearrangement of N-protected L-asparagine and L-glutamine. This method enabled the preparation of a diverse family of non-canonical amino acids (ncAAs) bearing side chains with varied properties, including electron-donating/accepting ability, redox activity, and fluorescence. The luminescence properties and redox behavior of these ncAAs were investigated. Furthermore, the newly synthesized Fmoc-protected ncAAs were successfully incorporated into a hexapeptide sequence using solid-phase peptide synthesis (SPPS), thus expanding the library of hexapeptide hydrogelators.

We present a convenient and efficient approach for synthesizing lysine homologs via the Hofmann rearrangement of N ‐protected L ‐asparagine and L ‐glutamine. This method enabled the preparation of a diverse family of noncanonical amino acids (ncAAs) bearing side chains with varied properties, including electron‐donating and electron‐accepting abilities, redox activity, and fluorescence. The luminescence properties and redox behavior of these ncAAs were investigated. Furthermore, the newly synthesized Fmoc‐protected ncAAs were successfully incorporated into a hexapeptide sequence using solid‐phase peptide synthesis, thus expanding the library of hexapeptide hydrogelators.