Gliadin/pectin hybrid nanoparticles for improved oral bioavailability of amphotericin B for the treatment of fungal infections.

Amphotericin B (AmB) is a broad-spectrum antifungal agent whose clinical use is limited by its poor oral bioavailability and dose-dependent toxicity. In this study, gliadin/pectin nanoparticles (GLI/PEC/AmB NP) were developed as a biopolymer-based oral delivery system for AmB. The nanoparticles obtained by nanoprecipitation exhibited a mean size of 398 ± 25 nm, polydispersity index of 0.24 ± 0.04, and zeta potential of -32 ± 3 mV, and encapsulation efficiency of 87 ± 4 %. FTIR, DSC and XRD analyses confirmed amorphization and molecular dispersion of AmB within the polymeric matrix. Under simulated gastrointestinal conditions, drug release was limited to 6 % in acidic medium and reached 79 % at 96 h in neutral buffer, following Weibull kinetics consistent with Fickian diffusion. UV-Vis spectra suggested reduced H-aggregation and preservation of the monomeric form. Mucin-binding assays demonstrated high affinity (>90 %) and Langmuir-type adsorption, confirming strong mucoadhesive potential of the gliadin/pectin hybrid. For nanoparticles than free AmB (p < 0.05), confirming enhanced mucoadhesion. In vitro antifungal assay against Candida albicans, C. tropicalis, and C. krusei showed concentration-dependent inhibition and morphological damage comparable to free AmB at 1.0 μg/mL. Hemolysis was reduced by 70 % and Vero cell viability remained >88 % indicating improved biocompatibility. Pharmacokinetic evaluation in rats revealed a 1.7-fold increase in Cmax and 1.6-fold higher AUC0-24h compared with oral AmB-deoxycholate, confirming enhanced systemic exposure and oral bioavailability. Collectively, these results demonstrate that GLI/PEC/AmB NP provide a stable, mucoadhesive, and biocompatible platform for effective oral delivery of AmB, warranting further investigation in vivo antifungal efficacy models.