Supramolecular phenoxy-alkyl maleate-based hydrogels and their enzyme/pH-responsive curcumin release

Abstract

Low-molecular-weight gelators that self-assemble via non-covalent interactions have been attracting significant attention due to their good biocompatibility, low toxicity, inherent biodegradability as well as their convenience of design. Enzymatically digestible and pH-sensitive hydrogels play an important role in controlled drug delivery applications. In the present study, we synthesized four simple phenoxy alkyl maleate amphiphiles with various hydrophobic chain lengths (C₆–C₁₂). The gelation ability of four amphiphiles was examined in a phosphate buffer solution; among them, the maleates with C₁₀ and C₁₂ chain lengths exhibited gelation ability at the minimum gelation concentrations (MGC) of 1.6 and 1.3% w/v, respectively. These hydrogelators have shown strong three-dimensional cross-linked networks that can capture water molecules. The obtained supramolecular hydrogels were thoroughly characterized using differential scanning calorimetry (DSC), scanning electron microscopy, density functional theory (DFT) calculation, X-ray diffraction, and rheological studies. More importantly, curcumin, a hydrophobic drug, was encapsulated (1% w/v) into the gel core, and its subsequent release was achieved through gel-to-sol transition induced by lipozyme (biological stimuli). Additionally, the drug-loaded hydrogel exhibited pH-responsive drug release behavior. The drug release behavior was monitored by employing UV-Vis spectroscopy. Overall, the prepared hydrogelators may be useful in the stimuli-responsive delivery of hydrophobic drugs.