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18. Development and characterization of oral liposomes of vegetal ceramide based amphotericin B having enhanced dry solubility and solubility.

Author

Skiba-Lahiani, Malika, Hallouard, François, Mehenni, Lyes, Fessi, Hatem, and Skiba, Mohamed

Subjects
*MYCOSES, *COMMUNICABLE disease treatment, *LIPOSOMES, *CERAMIDES, *AMPHOTERICIN B, *SOLUBILITY, *ANTIFUNGAL agents
Abstract

Despite the development of new antifungal, amphotericin B remains one of the most effective agents in the treatment of systemic fungal infections. Many patients exhibit nevertheless intolerance to amphotericin B at higher dosages and parenteral formulations present unlike per os ones, associated risks and high care cost. Free amphotericin B per os showed however an apparently poor absorption. In this study, we evaluate the potential of amphotericin B liposomes formulated with vegetal ceramides for oral administration. Ceramides, one of the constituents of cellular cytoplasmic membranes, constitute an important element in the construction and stability of their lipid bilayer. To fulfill this objective, vegetal ceramides, composed essentially of glucosylceramides, were firstly incorporated in various liposome preparations, entrapping or not amphotericin B, in comparison with phosphatidylcholine liposomes. Then, these preparations were introduced in an “Artificial-Stomach–Duodenum” model to improve their stability for oral administration. The formulation of amphotericin B liposomes containing ceramides presented a mean hydrodynamic size of about 200 nm. We showed also that cholesterol and phospholipids are required to prevent drug leakage and to obtain lamellar structure respectively. In “Artificial-Stomach–Duodenum” model, ceramides conferred to liposomes better membrane stability. In addition, ceramides did not alter their drug encapsulation yield being by 75%. This could be explained by the fact that ceramides as we proved, limited the detergent effect of bile salts on liposome membranes. [ABSTRACT FROM AUTHOR]

Published
2015
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