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Development of liposomal polyene antibiotics: an historical perspective
Agatha W K Ng1, Kishor M Wasan, Gabriel Lopez-Berestein
1Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Purpose:
The purpose of this review article is to review the development of a number of liposomal polyene antibiotics.
Background:
In the past thirty years, the increase in life-threatening pre-systemic and systemic fungal infections within cancer, diabetic and AIDS patients have reached alarming proportions. A number of antifungal agents have been developed to combat this problem. In particular, polyene antibiotics such as Amphotericin B (AmB) and Nystatin (Nys) have remained the most effective and widely used agents in the treatment of these infections. However, their administration is limited by dose-dependent toxicities. One such dose-limiting toxicity is renal toxicity. Polyene antibiotic-induced renal toxicity is believed to be mediated by the drug anchoring to cholesterol within the mammalian cell membrane, resulting in pore formation, abnormal electrolyte flux, decrease in adenosine triphosphate (ATP), and eventually a loss of cell viability.
Conclusion:
In the 1980s and 90s a number of promising lipid-based AmB and Nys formulations were developed to overcome these toxicities. This article will review the development of these liposomal polyene antibiotics.
Insights
Liposomal formulations of Amphotericin B (AmB) and Nystatin (Nys) were developed to reduce the toxicity of these effective antifungal antibiotics. This review covers the advancements in liposomal polyene antibiotics for treating serious fungal infections.
Area of Science:
- Pharmaceutical Sciences
- Antimicrobial Agents
- Drug Delivery Systems
Background:
- Life-threatening fungal infections are increasing in immunocompromised patients (cancer, diabetes, AIDS).
- Polyene antibiotics, Amphotericin B (AmB) and Nystatin (Nys), are effective but have dose-limiting toxicities, notably renal toxicity.
- Renal toxicity is linked to polyene antibiotic interaction with cholesterol in mammalian cell membranes, causing cell damage.
Observation:
- Lipid-based formulations, including liposomal Amphotericin B (AmB) and Nystatin (Nys), emerged in the 1980s and 1990s.
- These formulations aimed to mitigate the toxicities associated with conventional polyene antibiotics.
- The development focused on improving the therapeutic index of these crucial antifungal agents.
Findings:
- Liposomal encapsulation alters the pharmacokinetic and pharmacodynamic properties of polyene antibiotics.
- Reduced nephrotoxicity and improved efficacy have been observed with certain liposomal formulations.
- Liposomal delivery systems offer a strategy to enhance the safety and effectiveness of established antifungal drugs.
Implications:
- Liposomal polyene antibiotics represent a significant advancement in managing invasive fungal infections.
- These formulations provide safer treatment options for vulnerable patient populations.
- Further research into novel liposomal drug delivery systems can lead to improved antifungal therapies.