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Formulation Strategies to Overcome Amphotericin B Induced Toxicity
Sanat Kumar Dash1, Derajram Benival2, Anil B Jindal1
1Department of Pharmacy, Birla Institute of Technology and Science Pilani (BITS Pilani), Pilani Campus, Pilani, Rajasthan 333031, India.
Molecular Pharmaceutics
|October 7, 2024
Summary
Fungal infections are a global health crisis. New formulations of Amphotericin B (AmB) aim to reduce its toxicity and improve antifungal treatment outcomes, though clinical success remains limited.
Area of Science:
- Mycology and Infectious Diseases
- Pharmacology and Drug Development
- Biotechnology
Background:
- Fungal infections represent a significant global health burden, characterized by high prevalence, mortality, diagnostic challenges, and increasing drug resistance.
- Amphotericin B (AmB), a polyene antibiotic used since 1960, exhibits broad-spectrum antifungal and antileishmanial activity by disrupting fungal cell membranes.
- Clinical application of AmB is hampered by severe nephrotoxicity, primarily due to its binding to mammalian sterols.
Purpose of the Study:
- To review strategies for mitigating Amphotericin B-induced toxicity.
- To evaluate the efficacy of novel AmB formulations in improving antifungal therapeutic outcomes.
- To discuss the translational gap between preclinical success and clinical performance of AmB formulations.
Main Methods:
- Review of literature on Amphotericin B formulations, including nanoformulations, self-assembled systems, prodrugs, and combination therapies.
- Analysis of studies investigating AmB's mechanism of action and toxicity pathways.
- Assessment of preclinical and clinical data for various AmB delivery systems.
Main Results:
- Various AmB formulations (nanoformulations, prodrugs, etc.) have shown promise in preclinical studies by reducing toxicity and improving drug delivery.
- These formulations aim to control AmB aggregation, enable sustained release, and modify pharmacokinetic profiles.
- Despite promising preclinical results, the clinical efficacy and safety improvements of these advanced AmB formulations have been largely insignificant.
Conclusions:
- Novel AmB formulations offer potential for enhanced antifungal therapy by reducing toxicity.
- Bridging the gap between preclinical promise and clinical reality requires further research and interdisciplinary collaboration.
- Optimizing Amphotericin B therapy at the clinical stage necessitates continued investigation and partnerships between researchers, clinicians, and industry.
Keywords:
Albumin based AmB formulationsAmB CochleatesAmB NanoformulationsAmB ProdrugsAmB self-assembled nanostructuresAmB targeted deliveryAmB toxicity mitigationAmB- mAb combination therapyAmphotericin BCholesterol based AmB formulationsMore Related Videos
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