Mechanoresponsive, proteolytically stable and biocompatible supergelators from ultra short enantiomeric peptides with sustained drug release propensity

Abstract

Stimuli-responsive low molecular weight hydrogelators attract immense interest from diverse segments of biomedicine and biotechnology. Distinctly, herein we report newly synthesized enantiomeric ultrashort peptides of general formula Me-(CH₂)₈-CO-NH-CH(X)-COOH, where X = CH₂Ph in hydrogelators I (L-Phe) and II (D-Phe) respectively, which display excellent self-assembling propensity in physiological buffer at room temperature. Interestingly these biomolecules were endowed with mechanoresponsiveness, injectability and high mechanical integrity as confirmed by rheological measurements. Importantly they revealed resistance towards proteolytic degradation. Indeed dose dependent cell viability studies using MTT assay in four different cell lines, namely PANC-1, S1, HCT-116 and MDAMB-231, further confirmed the biocompatibility of the hydrogelators in vitro. The structural aspect of β-sheets of the hydrogelators was concluded on the basis of temperature dependent NMR, IR, PXRD and computational studies. We developed a user friendly delivery system, hydrogel nanoparticles (HNPs), with our mechanoresponsive and biocompatible hydrogelators, as these particles exhibited promising influence due to their enhanced surface area. Also the HNPs revealed excellent drug release kinetics for the model drugs 5FU/doxorubicin under physiological conditions in a sustained manner depending on the physicochemical parameters of the drugs. Taking these results together we envision that our designed hydrogelators and the delivery vehicle generated therefrom might represent a promising tool for administration of significant drug concentrations at lesion sites for a prolonged period, thus providing a better strategy for quick pain relief, rapid recovery and reduced systemic side effects.