Nanogel-based antifungal drug delivery systems: Advances in design, characterization, therapeutic applications, and future directions

Fungal infections continue to impose a substantial global health burden, with limitations in conventional antifungal therapies including poor penetrability, systemic toxicity, and emerging drug resistance necessitating the development of more effective delivery platforms. Nanogels, defined as nanoscale three-dimensional crosslinked hydrophilic polymer networks, have emerged as innovative carriers capable of enhancing antifungal drug solubility, stability, and targeted delivery. Their tunable physicochemical properties, such as particle size (20–200 nm), stimuli responsiveness, high drug-loading capacity, and biocompatibility, enable improved permeation across biological barriers and controlled release at the site of infection. This review outlines the key features of nanogel systems, including their synthesis via physical (microfluidics, nanoemulsions, inverse nanoprecipitation) and chemical (covalent and non-covalent crosslinking, bioconjugation) methods, with additional emphasis on the integration of herbal bioactives and nanoemulsion-based matrices to enhance antifungal efficacy. Comprehensive characterization approaches such as particle size analysis, rheology, FTIR, SEM, drug release studies, and ex vivo skin permeation are discussed in relation to optimizing formulation performance. Notable findings demonstrate that Vitamin E TPGS-based nanogels significantly improve the dermal delivery of antifungal agents like amphotericin B, achieving up to 3.9-fold higher skin deposition and enhanced inhibitory activity. The broad applicability of nanogels extends beyond antifungal therapy to vaccine delivery, anti-inflammatory treatment, and CNS-targeted administration. Despite considerable progress, challenges related to toxicity, long-term stability, large-scale manufacturing, and regulatory approval persist. This review highlights current advancements and identifies future opportunities for targeted, stimuli-responsive, and combination nanogel systems to advance antifungal therapeutics.