The University of Texas System

The University of North Carolina at Chapel Hill

Southern Research Institute

Rudolph L Juliano

Gabriel Lopez-Berestein

Reeta Mehta

Roy L Hopfer

Kapil Mehta

Evan M Hersh

Xin Ming

Victor Fainstein

Joseph A Maddry

Bing Yang

William Perry Janzen

Lindsey James

Canhong Cao

Silvia M Kreda

Ranathunga Arachchillage Yamuna Kumari Ariyarathna

Ling Wang

This disclosure is directed to methods, compounds and compositions for delivering nucleic acids to a cell of interest. In particular, it provides salts that are particularly effective in delivering nucleic acids to cells in the lung for disorders such as cystic fibrosis (CF).

Benzimidazoles that enhance the activity of oligonucleotides

Methods of administering an oligonucleotide of interest into a cell in vitro or in vivo are described. In the methods, a small organic compound active agent is concurrently administered to the cell in an amount effective to increase the delivery of the oligonucleotide into the cell, and/or increase the activity of said oligonucleotide in the cell. Compositions useful for carrying out the method are also described.

Small molecules that enhance the activity of oligonucleotides

The present invention involves a liposomal agent for treating disseminated fungal infection in an animal. This liposomal agent comprises the polyene antifungal compound mepartricin. The mepatricin is encapsulated within a liposome. The liposome in which the mepartricin is incorporated is preferably a stable multilamellar vesicle. The liposome broadly comprises one or more lipids one or more of phosphomonoglyceride, phosphatidic acid and sphingolipid. The lipids are preferably one or more of phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, sphingomyelin or phosphatidic acid. The lipids are most preferably one or more of dimyristoylphosphatidylchlorine, dimyristoylphosphatidylglycerol, phosphatidylcholine and phosphatidylglycerol. The liposome of the present invention may comprise a sterol most preferably cholesterol. An important aspect of the present invention involves a method for treating disseminated fungal infection in an animal. This method comprises administering to an animal subject to disseminated fungal infection a fungicidally effective amount of mepartricin encapsulated within a liposome. The liposome is composed as described above. The administering is preferably parenteral in most instances but may be oral or topical if specific colonies of fungus are thereby more directly reached. This treatment method is most useful when the animal is a human suffering from disseminated fungal infection. The method of treatment involves a fungicidally effective amount of liposome-incorporated mepartricin of between about 1 mg mepartricin/kg body weight and about 6 mg mepartricin/kg body weight.

Liposome-incorporated mepartricin

A method is disclosed for treatment of disseminated fungal infection in a mammal comprising the administration of a fungicidally effective amount of Amphotericin B encapsulated in a substantially sterol-free liposome to the infected mammal. Also provided is an agent for treatment of disseminated fungal infection in a mammal comprising Amphotericin B encapsulated in a liposome which consists essentially of lipids other than sterols.

Composition and method for treatment of disseminated fungal infections

The present invention involves a liposomal agent for treating disseminated fungal infection in an animal. This liposomal agent comprises the polyene antifungal compound nystatin. The nystatin is encapsulated within a liposome. The liposome in which the nystatin is incorporated is preferably a stable multilamellar vesicle. The liposome broadly comprises one or more lipids one or more of phosphomonoglyceride, phosphatidic acid and sphingolipid. The lipids are preferably one or more of phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, sphingomyelin or phosphatidic acid. The lipids are most preferably one or more of dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol, phosphatidylcholine and phosphatidylglycerol. The liposome of the present invention may comprise a sterol most preferably cholesterol. An important aspect of the present invention involves a method for treating disseminated fungal infection in an animal. This method comprises administering to an animal subject to disseminated fungal infection a fungicidally effective amount of nystatin encapsulated within a liposome. The liposome is composed as described above. The administering is preferably parenteral in most instances but may be oral or topical if specific colonies of fungus are thereby more directly reached. This treatment method is most useful when the animal is a human suffering from disseminated fungal infection. The method of treatment involves a fungicidally effective amount of liposome-incorporated nystatin of between about 1 mg nystatin/kg body weight and about 6 mg nystatin/kg body weight. In a most preferred embodiment the treatment method comprises liposomes consisting essentially of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a ratio of about 7:3.

Liposome-incorporated nystatin

Method for treatment of disseminated fungal infection in a mammal comprising the administration of a fungicidally effective amount of Amphotericin B encapsulated in a substantially sterol-free liposome to the infected mammal. Also provided is an agent for treatment of disseminated fungal infection in a mammal comprising liposome-encapsulated Amphotericin B, said liposome being comprised of lipids other than sterols.

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Chapel Hill, NC, United States of America

Rudolph L Juliano