Research ArticlesAmphotericin B in Oil–Water Lecithin-Based Microemulsions: Formulation and Toxicity Evaluation
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INTRODUCTION
Amphotericin B (AmB) is a macrocyclic, polyene antibiotic with a potent fungistatic and fungicidal activity against a broad range of pathogenic and opportunistic fungal species, and since its introduction in 1956 it has remained the most effective systemic therapy for serious fungal infections such as candidiasis, histoplasmosis, and aspergillosis.1,2 The incidence of these infections has increased in recent years due to frequent use of indwelling intravascular cathethers, immunossuppressive
Materials and Chemicals
All chemicals were used as received. Sodium hydroxide was obtained from Panreac (Barcelona, Spain). Isopropyl myristate (IPM) was obtained from Merck Schuchardt (Madrid, Spain). Polyoxyethylene-10-oleyl ether (Brij® 96V) was obtained from Fluka Chemika (Madrid, Spain). L-α-phosphatidyl-choline (L-α-Lecithin) was obtained from Sigma. Amphotericin B and Fungizone® (AmB) were a gift from Squibb Pharmaceutical Industry (Barcelona, Spain). Triple-distilled water, obtained from a Milli-Q Plus system
RESULTS AND DISCUSSION
Microemulsion components were IPM, water, lecithin and Brij® 96V. Lecithin, a nontoxic, naturally occurring biological surfactant, is a major component of membrane lipids. When administered in optimum amounts, it does not have the toxicity and sensitivity problems associated with most other surfactants. Hence, it is the ideal surfactant choice for preparing pharmaceutically acceptable microemulsions, especially via the parenteral route.21 Lecithin could not be used as surfactant alone because
CONCLUSIONS
The results presented in this article demonstrate that AmB microemulsions present optimal characteristics to be administered by the parenteral route. Their mean particle size, pH, and viscosity make them highly attractive carrier systems for the controlled delivery of AmB. It has also been demonstrated that AmB microemulsions were less toxic than was Fungizone®, suggesting its potential therapeutic application.
Acknowledgements
This work was supported by a grant from the Science and Education Ministry and by a grant No. 99/0853 from the National Fonds for Health Investigation (FIS). We also would like to acknowledge David Castro for valuable comments and critical reading of the manuscript.
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