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<p>Amphotericin B (AmB), a potent antifungal, suffers from poor aqueous solubility, low oral bioavailability, and dose-limiting toxicity. This study reports the development and characterization of a turmeric essential oil (TEO)-based oil-in-water nanoemulsion (NEA) encapsulating AmB to enhance solubility, stability, and therapeutic performance. The formulation, composed of TEO, Tween 80, and PEG-400, was optimized using pseudo-ternary phase diagrams and high-energy ultrasonication. The optimized NEA exhibited a pale-yellow appearance, mean droplet size of 79.1&#xa0;nm, polydispersity index (PDI) of 0.336, and zeta potential of − 4.3 mV. Viscosity (81.03 ± 1.35 cp.), refractive index (1.402 ± 0.07), and high transmittance (90.54 ± 0.18%) confirmed clarity and stability. Electrical conductivity (512.746 ± 3.024 µS/cm) indicated an oil-in-water type system. FTIR, UV–Vis, and XPS analyses confirmed AmB encapsulation, molecular interactions at the oil–water interface, and suppression of drug aggregation. TEM imaging showed spherical, uniform droplets with higher electron density in NEA than in the blank NE. Stability studies revealed minimal changes in droplet size, PDI, and zeta potential over 90 days under refrigerated conditions. AmB content was 95.46 ± 0.05%, with no visible precipitation after centrifugation, and encapsulation efficiency exceeded 80%. In vitro release studies showed a sustained drug release (63% over 48&#xa0;h), fitting best to the Higuchi model (R² = 0.9967), indicating Fickian diffusion control. Hemolytic assays confirmed excellent blood compatibility (&lt; 10% hemolysis at 100 µL/mL). Antifungal assays demonstrated potent activity against <i>Candida albicans</i>, <i>Aspergillus flavus</i>, and <i>Aspergillus niger</i>, with MIC values lower than free AmB. The synergistic contribution of the inherent antimicrobial properties of TEO might further enhance efficacy. The findings suggest that the TEO-based NE platform offers improved solubility, stability, and controlled drug release, with potential to reduce dosing frequency and toxicity. This natural oil-based nanoemulsion system represents a biocompatible and patient-friendly strategy with potential for future scale-up, and shows promising applications in oral and topical antifungal delivery.</p> Graphical Abstract <p>Schematic illustration of the formulation and therapeutic performance of an Amphotericin B–loaded turmeric oil nanoemulsion stabilized with Tween 80</p> <p></p>

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Development of a Turmeric Essential Oil-Based Nanoemulsion for Amphotericin B with Improved Solubility, Sustained Release, and Synergistic Antifungal Efficacy

  • 期刊论文

  • 发表日期：

    2026年2月16日

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  • Divya Mathew,
  • Benny Thomas,
  • N. M. Sudheep,
  • Jewel Benny Thomas,
  • E. K. Radhakrishnan

摘要

Amphotericin B (AmB), a potent antifungal, suffers from poor aqueous solubility, low oral bioavailability, and dose-limiting toxicity. This study reports the development and characterization of a turmeric essential oil (TEO)-based oil-in-water nanoemulsion (NEA) encapsulating AmB to enhance solubility, stability, and therapeutic performance. The formulation, composed of TEO, Tween 80, and PEG-400, was optimized using pseudo-ternary phase diagrams and high-energy ultrasonication. The optimized NEA exhibited a pale-yellow appearance, mean droplet size of 79.1 nm, polydispersity index (PDI) of 0.336, and zeta potential of − 4.3 mV. Viscosity (81.03 ± 1.35 cp.), refractive index (1.402 ± 0.07), and high transmittance (90.54 ± 0.18%) confirmed clarity and stability. Electrical conductivity (512.746 ± 3.024 µS/cm) indicated an oil-in-water type system. FTIR, UV–Vis, and XPS analyses confirmed AmB encapsulation, molecular interactions at the oil–water interface, and suppression of drug aggregation. TEM imaging showed spherical, uniform droplets with higher electron density in NEA than in the blank NE. Stability studies revealed minimal changes in droplet size, PDI, and zeta potential over 90 days under refrigerated conditions. AmB content was 95.46 ± 0.05%, with no visible precipitation after centrifugation, and encapsulation efficiency exceeded 80%. In vitro release studies showed a sustained drug release (63% over 48 h), fitting best to the Higuchi model (R² = 0.9967), indicating Fickian diffusion control. Hemolytic assays confirmed excellent blood compatibility (< 10% hemolysis at 100 µL/mL). Antifungal assays demonstrated potent activity against Candida albicans, Aspergillus flavus, and Aspergillus niger, with MIC values lower than free AmB. The synergistic contribution of the inherent antimicrobial properties of TEO might further enhance efficacy. The findings suggest that the TEO-based NE platform offers improved solubility, stability, and controlled drug release, with potential to reduce dosing frequency and toxicity. This natural oil-based nanoemulsion system represents a biocompatible and patient-friendly strategy with potential for future scale-up, and shows promising applications in oral and topical antifungal delivery.

Graphical Abstract

Schematic illustration of the formulation and therapeutic performance of an Amphotericin B–loaded turmeric oil nanoemulsion stabilized with Tween 80