Enhanced Antifungal Efficacy through Controlled Delivery of Amphotericin B Loaded in Polyetheramine-Epoxide Nanogels

Polymeric nanomaterials have emerged as promising carriers for drug delivery systems, offering improved therapeutic efficacy and reduced toxicity. In this study, we present an environmentally friendly and scalable approach for engineering nanogels as an innovative delivery platform for Amphotericin B (AmB), which is a potent antifungal agent. The nanogel system, named NanoT, was synthesized via an amine–epoxide reaction, enabling effective encapsulation and sustained release of AmB. Comprehensive physicochemical characterization was conducted using transmission electron microscopy (TEM), dynamic light scattering (DLS), ζ potential analysis, proton nuclear magnetic resonance (1H-NMR), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and synchrotron-based ultra-small angle X-ray scattering (USAXS). These analyses confirmed the successful formation of spherical nanogels and provided insights into their structural features. Additionally, molecular simulations indicated noncovalent interactions between AmB and the nanogel particles, supporting polymer-drug interactions. The NanoT system achieved an AmB loading capacity of approximately 55%. Notably, encapsulation promoted the formation of AmB superaggregates, which facilitated a controlled release of the active drug, leading to a 4-fold enhancement in antifungal activity. Mechanistic studies suggest that the antifungal efficacy of NanoT is attributed to both the sustained release of AmB and the electrostatic interactions with fungal cell surfaces. Overall, this study demonstrates the potential of amine–epoxide-based nanogels as effective carriers for antifungal therapeutics and contributes significantly to the development of advanced polymer-based drug delivery systems.