Stimuli-responsive supramolecular gels from fatty acid amides for theophylline delivery and anticancer applications ☆
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Date
2026
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Abstract
Supramolecular gels derived from low-molecular-weight gelators (LMWGs) uniquely combine features of both
homogeneous and heterogeneous systems, making them highly valuable in synthetic and medicinal chemistry.
Their rising prominence in cancer therapy is attributed to their excellent biocompatibility, stimuli-responsive
behavior, and ability to deliver anticancer drugs directly to tumor sites-reducing systemic side effects and
improving treatment efficacy. In this study, a series of fatty acid amide-based gelators (3a-3h) were synthesized
through a one-step amidation of 4-aminopyridine, with alkyl chain lengths varying from C
6
to C
22
. These gelators
formed stable organo/hydrogels in DMSO/water at low minimum gelation concentrations (1 % w/v), qualifying
as supergelators. Longer alkyl chains enhanced gelation and thermal stability due to synergistic interactions
between amide groups and hydrophobic segments. Specifically, gelators 3e and 3h demonstrated effective
encapsulation of the hydrophilic drug theophylline, facilitating controlled, pH-responsive release at physiological
temperature without compromising drug integrity. Cytotoxicity assays of these gelators demonstrated promising
anticancer activity against A549 lung cancer cells, along with low toxicity in normal Vero cells. Furthermore, the
synergistic anticancer efficacy of the theophylline-loaded gel formulations (3e + Th and 3h + Th) showed
enhanced potency, with IC
50
values of 12.89 ± 0.4 and 21.50 ± 2.8
potential as advanced drug delivery systems for cancer therapy.
μ
g/mL, respectively, highlighting their