Fluorinated diphenylalanine analogue based supergelators: a stencil that accentuates the sustained release of antineoplastic drugs

Abstract

Inspired by the prolonged metabolism displayed by para substituted fluorinated drugs, we intended to design two isomers Fmoc-(4F)-Phe-Phe-OH (hydrogelator I) & Fmoc-(3F)-Phe-Phe-OH (hydrogelator II) to explore the propensity of fluorine substitution in the aromatic ring of phenylalanine, in assisting or disrupting the gelation phenomena. However, our experimental observation reveals that hydrogelator I and II containing fluorines in the aromatic core illustrates excellent hydrogelation ability in comparison to the unsubstituted analogue, in accordance with the computational findings. Indeed, the hydrogelators displayed b-sheet with a fibrillar tape like morphology and were found to be biocompatible. We developed hydrogel nanoparticles (HNPs) that exhibited particle size less than 200 nm, and were found to release the antineoplastic drugs, 5Fluorouracil, curcumin and doxorubicin in a sustained manner depending on the architectural parameters of the drugs. Thus the prospective use of these compounds holds immense promise as a potential tool for future drug delivery applications.