Anion-responsive self-assembled hydrogels of a phenylalanine–TREN conjugate allow sequential release of propranolol and doxorubicin. Issue 40 (6th October 2022)

• Record Type: Journal Article
• Authors: Pradhan, Manas Kumar; Gupta, Deepika; Namdev, Kavthekar Rupesh; Anjali, ; Miglani, Chirag; Pal, Asish; Srivastava, Aasheesh
• Is Part Of: Nanoscale. Volume 14:Issue 40(2022)
• Page Start: 15079
• Page End: 15090
• Publication Date: 2022-10-06
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d2nr04320c
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Self-assemblies of a phenylalanine–TREN conjugate undergo anion-responsive nanofiber-to-nanoglobule transformation and its hydrogels allow sequential release of entrapped drugs. Abstract : Stimuli-responsive self-assembled and supramolecular hydrogels derived from peptide amphiphiles have opened exciting new avenues in biomedicine and drug delivery. Herein, we screened a series of phenylalanine-amphiphiles possessing polyamine and oxyethylene appendages for their self-assembly and anion-responsiveness and found that the tris(aminoethyl)amine (TREN) containing amphiphile NapF-TREN formed injectable hydrogels that could be disrupted upon the addition of stoichiometric amounts of tetrahedral monovalent anions such as H2 PO4 − and HSO4 −, while the addition of other anions such as Cl −, HPO4 2−, CO3 2−, HCO3 − or SO4 2− did not affect the gel stability. The anion–gelator interaction was investigated by 1 H and 31 P NMR spectroscopy as well as by Isothermal Titration Calorimetry (ITC). These studies confirmed a 1 : 1 stoichiometry and revealed negative enthalpy and negative entropy for the binding of H2 PO4 − with NapF-TREN. Microscopic investigations by TEM, AFM, and SAXS revealed that H2 PO4 − anions induced a nanofiber-to-nanoglobule morphological change in the aqueous self-assemblies of NapF-TREN. However, upon ageing the samples, slow reformation of the nanofibers was also observed, reflecting the reversibility of the anion–gelator interaction. The anion- and pH-responsive nature of the NapF-TREN hydrogels was exploited to program sequential release of entrapped drugs propranolol and doxorubicin.