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Could the Lung Be a Gateway for Amphotericin B to Attack the Army of Fungi?
Beatriz Ferreira de Carvalho Patricio1,2, Juliana Oliveira da Silva Lopes Pereira1, Michelle Alvares Sarcinelli3
1Pharmacology Laboratory, Biomedical Institute, Federal University of State of Rio de Janeiro, 94 Frei Caneca Street, Rio de Janeiro 20211-010, Brazil.
Abstract:
Fungal diseases are a significant cause of morbidity and mortality worldwide, primarily affecting immunocompromised patients. Aspergillus, Pneumocystis, and Cryptococcus are opportunistic fungi and may cause severe lung disease. They can develop mechanisms to evade the host immune system and colonize or cause lung disease. Current fungal infection treatments constitute a few classes of antifungal drugs with significant fungi resistance development. Amphotericin B (AmB) has a broad-spectrum antifungal effect with a low incidence of resistance. However, AmB is a highly lipophilic antifungal with low solubility and permeability and is unstable in light, heat, and oxygen. Due to the difficulty of achieving adequate concentrations of AmB in the lung by intravenous administration and seeking to minimize adverse effects, nebulized AmB has been used. The pulmonary pathway has advantages such as its rapid onset of action, low metabolic activity at the site of action, ability to avoid first-pass hepatic metabolism, lower risk of adverse effects, and thin thickness of the alveolar epithelium. This paper presented different strategies for pulmonary AmB delivery, detailing the potential of nanoformulation and hoping to foster research in the field. Our finds indicate that despite an optimistic scenario for the pulmonary formulation of AmB based on the encouraging results discussed here, there is still no product registration on the FDA nor any clinical trial undergoing ClinicalTrial.gov.
Insights
Pulmonary delivery of Amphotericin B (AmB) offers a promising strategy for treating fungal lung infections, especially in immunocompromised patients. Research explores nanoformulations to improve AmB lung delivery, though no FDA-approved products are currently available.
Area of Science:
- Medical Mycology
- Pulmonary Drug Delivery
- Nanotechnology in Medicine
Background:
- Fungal infections cause significant global morbidity and mortality, particularly in immunocompromised individuals.
- Opportunistic fungi like Aspergillus, Pneumocystis, and Cryptococcus pose severe lung disease risks.
- Antifungal drug resistance is a growing concern, highlighting the need for alternative treatments.
Purpose of the Study:
- To review strategies for pulmonary Amphotericin B (AmB) delivery.
- To explore the potential of nanoformulations for nebulized AmB.
- To encourage further research into inhaled AmB therapies.
Main Methods:
- Literature review of pulmonary AmB delivery strategies.
- Analysis of nanoformulation approaches for nebulized AmB.
- Examination of the advantages of the pulmonary route for drug administration.
Main Results:
- Nebulized AmB administration offers advantages like rapid onset and reduced systemic toxicity compared to intravenous routes.
- Nanoformulations show potential for enhancing AmB lung deposition and efficacy.
- Despite promising research, no AmB pulmonary products are FDA-registered, and no clinical trials are listed on ClinicalTrials.gov.
Conclusions:
- Pulmonary delivery, particularly via nanoformulations, presents a viable strategy for optimizing AmB treatment of fungal lung infections.
- Further research and clinical development are necessary to translate these findings into approved therapies.
- Addressing the challenges in AmB solubility, stability, and delivery is crucial for clinical success.
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