A novel performing PEG-cholane nanoformulation for Amphotericin B delivery.

Area of Science:

• Pharmaceutical Sciences
• Polymer Chemistry
• Mycology

Background:

• Amphotericin B (AmB) is a vital antifungal agent with poor solubility and significant toxicity.
• Developing effective drug delivery systems is crucial for improving AmB's therapeutic index.
• Micellar formulations offer a promising approach to enhance solubility and reduce side effects.

Purpose of the Study:

• To develop and characterize a novel micellar formulation of amphotericin B (AmB) using PEG 5kDa-cholane.
• To evaluate the solubility, stability, and antifungal activity of the new AmB formulation.
• To compare the performance of the novel formulation with Fungizone® and AmB in buffer.

Main Methods:

• Synthesis and characterization of PEG 5kDa-cholane micelles.
• Solubility, dynamic light scattering, and transmission electron microscopy for micelle analysis.
• Isothermal titration calorimetry, FT-IR, DSC, and X-ray diffractometry for interaction studies.
• Stability studies, serum albumin interaction assays, and in vitro antifungal activity tests against Candida albicans.

Main Results:

• PEG 5kDa-cholane dramatically increased AmB solubility by 1000-fold, forming 30 nm micelles.
• The freeze-dried formulation was easily re-dispersed, maintaining micelle integrity and stability for over a month.
• The AmB/PEG 5kDa-cholane formulation exhibited slower AmB disaggregation in serum albumin and 15% higher antifungal activity than AmB in buffer.

Conclusions:

• PEG 5kDa-cholane effectively forms stable micelles with amphotericin B, significantly enhancing its solubility and stability.
• The novel formulation demonstrates improved biopharmaceutical properties and enhanced antifungal efficacy.
• This micellar delivery system represents a promising advancement for amphotericin B therapy, potentially reducing toxicity and improving treatment outcomes.