Amphotericin B-cholesterol Co-encapsulated Polymeric Nanoparticles in Protein Hydrogel-based Injectable Depot System...

Area of Science:

• Pharmacology and Drug Delivery
• Nanotechnology in Medicine
• Biomaterials Science

Background:

• Amphotericin B is a vital antifungal but causes significant dose-dependent nephrotoxicity and hepatotoxicity due to cholesterol interactions.
• Current formulations necessitate careful dosing to balance efficacy and toxicity.
• Developing advanced delivery systems is crucial for improving Amphotericin B's therapeutic index.

Purpose of the Study:

• To create an injectable albumin hydrogel co-encapsulating Amphotericin B and cholesterol.
• To achieve prolonged plasma drug concentrations and reduce Amphotericin B-induced toxicity.
• To evaluate the physicochemical properties, drug release kinetics, and in vivo safety of the novel formulation.

Main Methods:

• Amphotericin B-loaded polymeric nanoparticles (Amphotericin B-PNs) were prepared using nanoprecipitation.
• Cholesterol was co-encapsulated within the nanoparticles to improve stability and reduce aggregation.
• Albumin hydrogel was formed via ethanol-induced gelation, incorporating the Amphotericin B-PNs for sustained release.

Main Results:

• The co-encapsulated nanoformulation demonstrated reduced Amphotericin B aggregation and hemolysis.
• The hydrogel formulation exhibited sustained drug release over 14 days, with ~60% released in the first week.
• Biochemical and oxidative stress assays indicated reduced organ toxicity and improved safety compared to conventional Amphotericin B.

Conclusions:

• The Amphotericin B-PN-loaded albumin hydrogel represents a promising injectable depot for sustained Amphotericin B delivery.
• This formulation enhances pharmacokinetic profiles and significantly mitigates Amphotericin B's characteristic toxicities.
• The developed system offers a potential strategy for safer, long-acting antifungal therapy.