Bolaamphiphilic Bis-Dehydropeptide Hydrogels as Potential Drug Release Systems

The self-assembly of nanometric structures from molecular building blocks is an effective

way to make new functional materials for biological and technological applications. In this work

four symmetrical bolaamphiphiles based on dehydrodipeptides

(phenylalanyldehydrophenylalanine and tyrosyldehydrophenylalanine) linked through phenyl

or naphthyl linkers (terephthalic acid and 2,6-naphthalenedicarboxylic acid) were prepared and

their self-assembly properties studied. The results showed that all compounds with the exception

of the bolaamphiphile of tyrosyldehydrophenylalanine and 2,6-naphthalene dicarboxylic acid

gave self-standing hydrogels with critical gelation concentrations of 0.3 and 0.4 wt% using a pH

trigger. The self-assembly of these hydrogelators was investigated using STEM microscopy,

which revealed a network of entangled fibres. According to rheology the dehydrodipeptide

bolaamphiphile hydrogelators are viscoelastic materials with an elastic modulus G’ that falls in

the range of native tissue (0.37 kPa brain – 4.5 kPa cartilage). In viability and proliferation studies,

it was found that these compounds were non-toxic towards the human keratinocyte cell line,

HaCaT. In sustained release assays, we studied the effects of the charge present on the model

drug compound on the rate of cargo release from the hydrogel networks. Methylene blue (MB),

methyl orange (MO) and ciprofloxacin were chosen as cationic, anionic and overall neutral cargo,

respectively. These studies have shown that the hydrogels provide a sustained release of methyl

orange and ciprofloxacin, while the methylene blue is retained by the hydrogel network.

Abstract