amphotericin B

Overview

Amphotericin B is a broad-spectrum polyene antifungal agent used for serious systemic fungal infections and, in some settings, for parasitic diseases such as cutaneous leishmaniasis. It is a clinically important drug because of its potent activity against a wide range of pathogenic fungi, including Candida species and invasive molds, and because it remains a key option when infections are severe, refractory, or life-threatening. In the recent literature provided, amphotericin B is described as an FDA-approved therapy with recognized efficacy but also with substantial toxicity concerns, particularly when administered systemically.

Its biological activity is generally attributed to binding ergosterol in fungal cell membranes, leading to membrane disruption and cell death. This mechanism underlies its use against invasive fungal disease, but the same membrane-associated effects also contribute to adverse reactions that have driven the development of improved formulations, especially liposomal amphotericin B. Recent research has continued to focus on balancing efficacy and toxicity through drug delivery innovations, combination therapy, and alternative administration routes.

Focus of Latest Publications

Recent publications have focused on amphotericin B as a formulation and delivery challenge, with several studies aiming to improve its therapeutic index by enhancing local delivery, stability, and tolerability. In ophthalmology, a bioresponsive nanocubosomal in situ gelling system was developed for amphotericin B delivery to treat fungal keratitis. The optimized formulation showed nanoscale particle size, high entrapment efficiency, colloidal stability, pH-triggered gelation at ocular pH, sustained in vitro release over 24 hours, stronger antifungal activity against Candida albicans than marketed Amfocare®, and no ocular irritation in rabbit Draize testing. The authors concluded that the system may help maintain amphotericin B in monomeric form while improving ocular retention and reducing irritation.

Other studies explored alternative routes to reduce systemic toxicity and improve access to difficult-to-treat infections. A hollow microneedle-based delivery approach was tested in mice with Leishmania mexicana–infected American cutaneous leishmaniasis lesions, where microneedle administration of Fungizone/amphotericin B limited lesion growth and reduced parasitic burden after treatment, without increases in serum creatinine or blood urea nitrogen. In a separate CNS-focused study, an HS15-based nanocomplex containing lecithin and cholesterol was designed for intranasal nose-to-brain delivery of amphotericin B. This formulation showed stable particle characteristics, good spray and placement stability, longer and higher intracerebral distribution in release and imaging studies, and minimal mucosal toxicity and nephrotoxicity, supporting intranasal delivery as a potential strategy for fungal infections of the central nervous system.

Amphotericin B also served as a comparator or combination partner in antimicrobial studies. A marine-derived fungal metabolite study found that compounds 1 and 15 enhanced amphotericin B activity against Candida albicans strains, including C. albicans ATCC 10231 and drug-resistant clinical isolates. In another antimicrobial paper, benzimidazole-based derivatives were compared with amphotericin B against Candida albicans, and two compounds showed lower MIC values than the reference drug. Additionally, a photodynamic inactivation study of Leishmania amazonensis reported parasite killing comparable to amphotericin B, underscoring its continued role as a benchmark antiparasitic agent.

Clinical literature in the recent set also reflects amphotericin B’s ongoing use in severe invasive fungal disease. A case report of breakthrough invasive pulmonary Coprinopsis cinerea infection in an immunocompromised patient described switching antifungal therapy to liposomal amphotericin B, followed by surgical resection and subsequent step-down therapy. Separately, a review of liposome-based drug delivery systems highlighted AmBisome® as a clinically established liposomal amphotericin B formulation that exemplifies how nanocarrier engineering can improve efficacy and reduce toxicity relative to conventional formulations.

Key Publications

May Development and in vivo evaluation of novel bioresponsive nanocubosomal in-situ gelling system for ophthalmic delivery of Amphotericin B. (International journal of pharmaceutics, 2026, PMID 42150646): "Amphotericin B (AmB), the drug of choice for fungal keratitis, displays poor aqueous solubility, physiological instability, and pH-dependent aggregation causing ocular irritation."
May Microneedle-based injection of Fungizone/Amphotericin B: an effective treatment for American cutaneous leishmaniasis in mice. (Drug delivery, 2026, PMID 42083326): "Amphotericin B (AmB) is a potent, accessible, FDA-approved drug against CL with damaging side effects."
Jun Furanocoumarin-rich extracts from Trichocline plicata as natural photosensitizers for the photodynamic inactivation of Leishmania amazonensis: Insights into ROS- and DNA-mediated mechanisms. (Journal of photochemistry and photobiology. B, Biology, 2026, PMID 42066647): "Photodynamic treatment reduced parasite viability by up to 97%, comparable to amphotericin B, and microscopy revealed severe morphological damage in irradiated parasites."
Apr Liposome-Based Drug Delivery Systems: Mechanisms, Preparation Strategies, Clinical Status, and Therapeutic Applications. (AAPS PharmSciTech, 2026, PMID 42026392): "Clinically established formulations such as Doxil® and AmBisome® are highlighted as representative examples demonstrating improved therapeutic efficacy and reduced toxicity compared with conventional formulations."
May Breakthrough invasive pulmonary Coprinopsis cinerea (Hormographiella aspergillata) infection successfully managed with antifungal therapy and surgical resection enabling cord blood transplantation. (Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2026, PMID 41895473): "Antifungal therapy was switched to liposomal amphotericin B."
Jun Design and synthesis of benzimidazole-based derivatives with antimicrobial activity: mechanistic insights into ROS-mediated oxidative damage, hemolytic assessment, and molecular docking studies. (Bioorganic chemistry, 2026, PMID 41831427): "In contrast, compounds 3c and 3i demonstrated pronounced antifungal potency against C. albicans, exhibiting MIC values of 8.2 ± 1.84 and 9.8 ± 1.92 μg/mL, respectively, outperforming the reference drug Amphotericin B (MIC = 11.8 ± 0.41 μg/mL)."
May HS15-based nanotherapeutics for direct nose-to-brain delivery against central nervous system fungal. (Journal of pharmaceutical sciences, 2026, PMID 41780885): "Amphotericin B (AmB) is a broad-spectrum antifungal drug, but its use in the treatment of fungal infections in the central nervous system (CNS) has been limited by the constraints of the blood-brain barrier (BBB) and the severe toxicity of systemic administration."
Jun Six previously undescribed bisabolane-type sesquiterpenes from marine derived fungus Aspergillus sp. WHUF04-170 and their antimicrobial activity. (Phytochemistry, 2026, PMID 41651325): "Notably, synergistic antimicrobial assays revealed that compounds 1 and 15 enhanced the activity of amphotericin B against Candida albicans strains..."