Enhanced Antifungal Activity by Ab-Modified Amphotericin B-Loaded Nanoparticles Using a pH-Responsive Block Copolymer

Area of Science:

• Nanotechnology
• Pharmaceutical Sciences
• Mycology

Background:

• Fungal infections pose significant risks to immunocompromised individuals.
• Amphotericin B (AMB) is a potent antifungal but limited by toxicity and pH-dependent efficacy.
• Localized acidity at infection sites reduces AMB effectiveness.

Purpose of the Study:

• To develop pH-responsive, surface charge-switching nanoparticles for improved AMB delivery.
• To enhance AMB's antifungal efficacy and reduce toxicity by overcoming pH-related limitations.
• To improve AMB targetability using antibody-conjugated nanoparticles.

Main Methods:

• Fabrication of poly(D,L-lactic-co-glycolic acid)-b-poly(L-histidine)-b-poly(ethylene glycol) (PLGA-PLH-PEG) nanoparticles loaded with AMB.
• Surface modification of nanoparticles with anti-Candida albicans antibody (CDA) to create CDA-AMB-NPs.
• Characterization of CDA-AMB-NPs for physical properties, drug release, stability, encapsulation efficiency, and toxicity.
• In vitro and in vivo evaluation of targetability and antifungal activity.

Main Results:

• CDA-AMB-NPs demonstrated enhanced targetability and bioavailability of AMB.
• The pH-responsive nanoparticles effectively addressed localized acidity issues.
• Significant improvement in antifungal activity and reduction in AMB toxicity were observed.
• Nanoparticle formulation showed good physical characteristics, stability, and encapsulation efficiency.

Conclusions:

• CDA-AMB-NPs represent a promising drug delivery system for enhancing AMB's therapeutic potential.
• This approach effectively overcomes AMB's limitations, including pH-dependent activity and toxicity.
• The developed nanoparticles offer a viable strategy for improving antifungal treatments in vulnerable patient populations.