Nanocomposite films of halloysite nanotubes with gellan gum for the delivery of terbinafine hydrochloride

Millions of people worldwide suffer from fungal infections, which are becoming more difficult to treat because of resistance, biofilm formation, and the limited effectiveness of current antifungal medications. Despite its widespread use, the well-known antifungal drug terbinafine hydrochloride (TRB) has drawbacks in terms of resistance and bioavailability. This work addresses these challenges not by altering genetic resistance pathways, but by enhancing drug delivery efficiency, sustained release, and permeability, thereby maintaining higher local drug concentration for prolonged periods and potentially improving performance against strains with reduced susceptibility. In this work, new nanocomposite films made of magnesium sulphate (MgSO₄), gellan gum (GG), halloysite nanotubes (HNTs), and TRB are developed and characterized. The purpose of the films was to increase antifungal potency, sustain release, and improve drug entrapment. Different ratios of drug-loaded HNTs integrated into a GG polymer matrix, with or without MgSO₄, were used to prepare the formulations. Scanning electron microscopy (SEM), X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) structural characterization verified successful incorporation, decreased crystallinity, and enhanced stability. In optimized formulations, entrapment efficiency was over 90% and drug loading ranged from 34% to 42%. Compared to the pure drug,
in vitro
tests showed significantly larger inhibition zones against
Aspergillus niger
(
A.N
) and
Candida albicans (C.A)
, as well as prolonged TRB release with non-Fickian diffusion kinetics. Rat intestinal mucosa penetration tests showed improved drug flux, especially in films loaded with MgSO₄. Increased half-life, plasma concentration, and bioavailability were demonstrated by pharmacokinetic evaluation
in vivo
, and toxicity studies verified safety without appreciable changes in hematology or biochemistry. These results demonstrate the potential of nanocomposite films as a drug delivery system, providing enhanced pharmacokinetics, long-lasting therapeutic effects, and synergistic antifungal activity. In the treatment of resistant fungal infections, such formulations might offer safer and more efficient substitutes.