eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-06-30 18 2 1559 1570 10.13005/bpj/3193 65671 article Sunidhi Lohan 1 Meenakshi Bhatia 1 Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, India Amphotericin B (BCS Class IV), an effective treatment for cutaneous leishmaniasis, has limited topical application due to poor skin penetration and stability. To overcome these challenges, this study aimed to formulate Amphotericin B-loaded nanostructured lipid carrier (NLC) gel to enhance drug encapsulation, stability, and controlled release. Amphotericin B-loaded NLCs were synthesized using a microwave-assisted method, which improved encapsulation efficiency and controlled particle size. The NLC dispersion was then incorporated into Carbopol 934 to form a gel. Characterization included particle size, zeta potential, morphology, spreadability, extrudability, in vitro drug release, ex-vivo skin permeation, and histopathological evaluation. The NLCs had a particle size of 180 nm, a polydispersity index of 0.32, and a zeta potential of –28.8 mV, ensuring stability. The Amphotericin B-NLC gel exhibited favorable physicochemical properties, including a smooth texture, a pH of 6.3, extrudability (9.5 ± 0.12 gm/cm²), and spreadability (6.4 cm). In vitro release studies demonstrated sustained release, with 48.05% drug release after 8 hours. The release kinetics followed the Higuchi model, indicating Fickian diffusion as the release mechanism. Ex-vivo permeation studies showed significantly enhanced skin permeation with the NLC and NLC gel formulations compared to the aqueous dispersion. Histopathological analysis indicated no signs of toxicity, with preserved skin integrity. The Amphotericin B-NLC gel formulation may significantly improve drug delivery for treating cutaneous leishmaniasis by enhancing skin penetration, providing controlled release, and demonstrating excellent safety. https://biomedpharmajournal.org/vol18no2/amphotericin-b-loaded-nanostructured-lipid-carrier-gel-preparation-and-evaluation-for-enhanced-skin-permeation/ Amphotericin B Histopathology Microwave Nanostructured Lipid Carriers Topical Drug Delivery