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|Title:||Method of treatment of infected tissues|
|Abstract:||A method of treating a site of systemic infection which includes administering a therapeutic compound entrapped in liposomes. Also included is a liposomal composition and a method of preparing a liposomal composition for use in concentrating a therapeutic compound to an infected region via the bloodstream. The liposomes, which contain the agent in entrapped form, are composed of vesicle-forming lipids, a vesicle-forming lipid derivatized with hydrophilic biocompatible polymer, and have sizes in a selected size range between 0.07 and 0.2 microns. After parenteral administration, the liposomes are selectively taken up by the infected region within 24-48 hours, for release of entrapped compound into the infected region.|
|Inventor(s):||Woodle; Martin C. (Menlo Park, CA), Bakker-Woudenberg; Irma A.J.M. (Bergschenhoek, NL), Martin; Francis J. (San Francisco, CA)|
|Assignee:||SEQUUS Pharmaceuticals, Inc. (Menlo Park, CA)|
|Filing Date:||Mar 27, 1992|
|Claims:||1. A method of treating a systemic infection which is localized at a site other than the fixed macrophages residing in the liver or the spleen, comprising |
administering to the subject, by intravenous injection, a composition of liposomes (i) composed of vesicle-forming lipids, including 1-35 mole percent of a diacyl-chain amphipathic vesicle-forming lipid derivatized with polyethylene glycol having a molecular weight between about 350 and 5,000 daltons (ii) having a selected mean particle diameter in the size range between about 0.07-0.20 microns, and (iii) containing in liposome-entrapped form, a therapeutic compound effective against the source of the infection, and
by said injecting, achieving at least about a ten-fold increase in the concentration of liposomes in the infected tissue over that achievable by the such liposomes in the absence of the amphipathic vesicle-forming lipid derivatized with said polyethylene glycol.
2. The method of claim 1, wherein the infection is bacterial in origin and the therapeutic compound is an antibiotic.
3. The method of claim 2, wherein at least about 60% of the antibiotic agent is in liposome-entrapped form.
4. The method of claim 1, wherein the antibiotic agent is an aminoglycoside antibiotic, the concentration of which entrapped in the liposomes is greater than 20 .mu.g compound/.mu.mole liposome lipid.
5. The method of claim 1, wherein the infection site is lung, the source of the infection is Klebsiella, and the therapeutic agent is gentamicin.
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