Treatment of systemic fungal infections with phospholipid particles encapsulating polyene antibiotics
First Claim
1. An injectable composition comprising a polyene antifungal antibiotic encapsulated in small unilamellar vesicles of less than 2000 Å
- in an amount of about 4 to about 12 mole percent, said vesicles comprising at least one phospholipid and cholesterol, hydrated in a low ionic strength aqueous phase composed of a mono or disaccharide, said composition being stable upon storage and having an acute intravenous toxicity (LD50) in mice greater than approximately 21.2 mg of said polyene antibiotic per kg of animal weight.
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Abstract
Formulations consisting of phospholipid small unilamellar particles encapsulating polyene antifungal antibiotics and methods for using such compositions to treat systemic fungal infections are described. In a preferred embodiment, the particles are in the form of vesicles which comprise a polyene antifungal antibiotic, preferably amphotericin B and/or nystatin, egg phosphatidylcholine and cholesterol, preferably in the molar ratio of about 0.2 (AMB):2(PL):1(CHOL). These vesicles may also have an amine modified surface. The vesicles are suspended in a low isonic strength saccharide/tris solution at a pH of from about 6.0 to about 8.0 and may be administered to deliver the antifungal antibiotic to treat systemic fungal infections.
55 Citations
26 Claims
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1. An injectable composition comprising a polyene antifungal antibiotic encapsulated in small unilamellar vesicles of less than 2000 Å
- in an amount of about 4 to about 12 mole percent, said vesicles comprising at least one phospholipid and cholesterol, hydrated in a low ionic strength aqueous phase composed of a mono or disaccharide, said composition being stable upon storage and having an acute intravenous toxicity (LD50) in mice greater than approximately 21.2 mg of said polyene antibiotic per kg of animal weight.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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12. An injectable composition comprising small unilamellar vesicles of less than 2000 Å
- which contain a polyene antifungal antibiotic in an amount of about 4 to about 12 mole percent prepared by a process comprising the steps of;
a) dissolving at least one phospholipid and cholesterol in an aliphatic alcohol having from four to eight carbon atoms; b) dissolving a polyene antifungal antibiotic in a solvent selected from the group consisting of dimethylsulfoxide or dimethylformamide; c) mixing the solutions of steps (a) and (b); d) evaporating the mixed solvents to produce a lipid cholesterol antibiotic mixture; e) hydrating the mixture with saccharide solution of low ionic strength; and f) forming small unilamellar vesicles containing the polyene antifungal antibiotic from the hydrated mixture. - View Dependent Claims (13, 14, 26)
- which contain a polyene antifungal antibiotic in an amount of about 4 to about 12 mole percent prepared by a process comprising the steps of;
Specification