Supramolecular peptide hydrogels have many important applications in biomedicine, including drug delivery applications for the sustained release of therapeutic molecules. Targeted and selective drug administration is often preferential to systemic drug delivery, as it can allow reduced doses and can avoid the toxicity and side-effects caused by off-target binding. New discoveries are continually being reported in this rapidly developing field. In this review, we report the latest developments in supramolecular peptide-based hydrogels for drug delivery, focusing primarily on discoveries that have been reported in the last four years (2018–present). We address clinical points, such as peptide self-assembly and drug release, mechanical properties in drug delivery, peptide functionalization, bioadhesive properties and drug delivery enhancement strategies, drug release profiles, and different hydrogel matrices for anticancer drug loading and release.

Gold nanoparticles functionalized with Gd³⁺ chelates displaying fast water exchange, superb pH stability and inertness towards transmetalation with Zn²⁺ have been prepared and characterized as a new high relaxivity (29 mM⁻¹ s⁻¹, 30 MHz, 25 °C) contrast agent potentially safe for in vivo MRI applications. The Lipari–Szabo treatment for internal rotation was used to evaluate the effect of linker flexibility on the relaxivity of the gold nanoparticles. The effect of fast water exchange on the relaxivity of gold nanoparticles functionalized with Gd³⁺ chelates is also addressed in this communication.

By using a 4-dimethylaminopyridine (DMAP) catalysed reaction of β-hydroxyamino acid derivatives with tert- butyl pyrocarbonate [(Boc)₂O], dehydroamino acid derivatives are obtained in high yields. The same methodology applied to dipeptides with a β-hydroxyamino acid residue gives the corresponding dipeptides with a dehydroamino acid residue.

A potential antitumoral fluorescent indole derivative, methyl 6-methoxy-3-(4-methoxyphenyl)-1H-indole-2-carboxylate, was evaluated for the in vitro cell growth inhibition on three human tumor cell lines, MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), and NCI-H460 (non-small cell lung cancer), after a continuous exposure of 48 h, exhibiting very low GI50 values for all the cell lines tested (0.25 to 0.33 μM). This compound was encapsulated in different nanosized liposome formulations, containing egg lecithin (Egg-PC), dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG), DSPC, cholesterol, dihexadecyl phosphate, and DSPE-PEG. Dynamic light scattering measurements showed that nanoliposomes with the encapsulated compound are generally monodisperse and with hydrodynamic diameters lower than 120 nm, good stability and zeta potential values lower than -18 mV. Dialysis experiments allowed to monitor compound diffusion through the lipid membrane, from DPPC/DPPG donor liposomes to NBD-labelled lipid/DPPC/DPPG acceptor liposomes.

Michael additions of nitrogen heterocycles, thiols, carbon nucleophiles and amines to dehydroalanine derivatives, including a glycyldehydroalanine peptide, are performed in fair to good yields. Didehydroaminobutyric acid derivatives react only with the stronger nucleophiles but in considerably lower yields and often no reaction is observed with the corresponding didehydrophenylalanine derivatives. When a tosyl group is bonded to the nitrogen atom of the dehydroamino acid, in some cases the addition product undergoes elimination of this group and yields the corresponding β-substituted derivative of the α,β-didehydroamino acid. Addition of some β-dicarbonyl compounds leads to formation of products to which the structure of α,α-disubstituted cyclic amino acid derivatives is assigned.