N‐Hydroxyalkanamide Based Organo/hydrogels as Novel Scaffolds for pH‐Dependent Metronidazole and Theophylline Release

Abstract

The traditional delivery of metronidazole and theophylline presents challenges like bitter taste, variable absorption, and side effects. However, gel‐based systems offer advantages including enhanced targeted drug delivery, minimized side effects, and improved patient compliance, effectively addressing these challenges. Consequently, a cost‐effective synthesis of N‐hydroxyalkanamide gelators with varying alkyl chain lengths was achieved in a single‐step reaction procedure. These gelators formed self‐assembled aggregates in DMSO/water solvent system, resulting in organo/hydrogels at a minimum gelation concentration of 1.5% w/v. Subsequently, metronidazole and theophylline were encapsulated within the gel core and released through gel‐to‐sol transition triggered by pH variation at 37 °C, while maintaining the structural‐activity relationship. UV‐vis spectroscopy was employed to observe the drug release behavior. Furthermore, in vitro cytotoxicity assays revealed cytotoxic effects against A549 lung adenocarcinoma cells, indicating anti‐proliferative activity against human lung cancer cells. Specifically, the gel containing theophylline (16HAD+Th) exhibited cytotoxicity on cancerous A549 cells with IC50 values of 19.23 ± 0.6 µg/mL, followed by the gel containing metronidazole (16HAD+Mz) with IC50 values of 23.75 ± 0.7 µg/mL. Moreover, the system demonstrated comparable antibacterial activity against both gram‐negative (E. coli) and gram‐positive bacteria (S. aureus).