Amphotericin B microspheres: a therapeutic approach to minimize toxicity while maintaining antifungal efficacy

Pawan K Angra1, Carl Oettinger, S Balakrishna Pai

  • 1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341, USA.

Insights

New amphotericin B microspheres show stable, safe, and effective antifungal properties. These novel drug delivery systems offer comparable efficacy to conventional formulations without increased toxicity.

Area of Science:

  • Pharmaceutical Sciences
  • Biomaterials Science
  • Mycology

Background:

  • Amphotericin B is a critical antifungal agent, but its use is limited by toxicity.
  • Microsphere formulations offer potential for improved drug delivery and reduced side effects.
  • Cross-linked bovine serum albumin provides a biocompatible matrix for drug encapsulation.

Purpose of the Study:

  • To prepare and characterize amphotericin B microspheres using cross-linked bovine serum albumin.
  • To evaluate the stability, drug release kinetics, in vitro toxicity, and antifungal activity of these novel formulations.
  • To assess the impact of polyethylene glycol 2000 addition on microsphere properties.

Main Methods:

  • Preparation of amphotericin B microspheres with and without polyethylene glycol 2000.
  • Characterization of microspheres for particle size, zeta potential, and drug-excipient interactions using DSC and FTIR.
  • Assessment of in vitro drug release profiles.
  • Evaluation of in vitro toxicity via haemoglobin and potassium release assays.
  • Determination of antifungal activity using the broth dilution method.

Main Results:

  • Microspheres exhibited a particle size below 5 micrometers and a zeta potential of approximately 30 mV.
  • DSC and FTIR analyses confirmed stable formulations with no significant drug-excipient degradation.
  • Drug release predominantly occurred via diffusion.
  • In vitro toxicity assessments showed no adverse effects compared to conventional amphotericin B solutions.
  • In vitro antifungal activity was comparable to the solution formulation.

Conclusions:

  • Amphotericin B microspheres formulated with cross-linked bovine serum albumin are stable and safe.
  • These microspheres demonstrate effective in vitro antifungal activity with a release mechanism primarily by diffusion.
  • The addition of polyethylene glycol 2000 did not negatively impact formulation stability or efficacy.

Related Concept Videos

Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...
Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
Anthelminthic Agents01:15

Anthelminthic Agents

Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
Fungal Phylum Microsporidia01:28

Fungal Phylum Microsporidia

Microsporidia are a group of obligate intracellular fungi that were initially classified as protists but were later reclassified based on phylogenetic, molecular, and structural evidence linking them to the Chytridiomycota. These unicellular, non-motile organisms are highly specialized parasites that infect a wide range of animal hosts, including humans. They have evolved extensive genomic and metabolic reductions, making them highly dependent on their hosts for survival.Morphology and Genomic...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...