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Mechanoresponsive, Proteolytically stable and Biocompatible Supergelators from Ultra Short Enantiomeric Peptides with sustained drug release propensity

Abstract

Stimuli-responsive low molecular weight hydrogelators invites immense interest from diverse segments of biomedices and biotechnology. Distinctly, herein we report the newly synthesized enantiomeric ultrashort peptides of general formula Me-(CH2)8-CO-NH-CH(X)-COOH, where X = CH2Ph in hydrogelator I (L-Phe) & II (D-Phe) respectively, that displays 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 dependant 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 structurall aspect sheet of the hydrogelators were concluded on the basis of temperature dependant NMR , IR, PXRD and computation 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 enhanced surface area. Also the HNPs revealed excellent drug release kinetics for the model drugs 5FU/Doxorubicin at physiological conditions in a sustained manner depending on the physicochemical parameters of the drugs. Taken together these results we envision that our designed hydrogelators and the delivery vehicle generated therefrom might represent a promising tool for administration of significant drug concentration at the lesion sites for prolonged period, thus providing a better strategy for quick pain relief, rapid recovery and reduced systemic side effects.

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Supplementary files

Article information


Submitted
08 Jan 2020
Accepted
04 Mar 2020
First published
05 Mar 2020

New J. Chem., 2020, Accepted Manuscript
Article type
Paper

Mechanoresponsive, Proteolytically stable and Biocompatible Supergelators from Ultra Short Enantiomeric Peptides with sustained drug release propensity

R. R. Mehra, A. Basu, R. M. Christman, J. Harjit, A. K. Mishra, A. Tiwari and A. DuttKonar, New J. Chem., 2020, Accepted Manuscript , DOI: 10.1039/D0NJ00102C

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