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lüll Development of liposomal polyene antibiotics: an historical perspective Ng AW; Wasan KM; Lopez-Berestein GJ Pharm Pharm Sci 2003[Jan]; 6 (1): 67-83PURPOSE: 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.|Adenosine Triphosphate/history/metabolism[MESH]|Amphotericin B/administration & dosage/adverse effects/history[MESH]|Animals[MESH]|Antifungal Agents/administration & dosage/adverse effects/*history[MESH]|Chemistry, Pharmaceutical/history[MESH]|Cholesterol/history/metabolism[MESH]|Drug Carriers/history[MESH]|Drug Delivery Systems/history[MESH]|History, 20th Century[MESH]|History, 21st Century[MESH]|Humans[MESH]|Liposomes/administration & dosage/*history[MESH]|Nystatin/administration & dosage/adverse effects/history[MESH]|Polyenes/chemistry/history[MESH] |