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Summary for Patent: 5,814,335
|Title:||Sphingosomes for enhanced drug delivery|
|Abstract:||Liposomal formulations having extended circulation time in vivo and increased drug retention are comprised of sphingomyelin and cholesterol and have an acidic intraliposomal pH. The formulations have enhanced stability and thus are used in methods which provide improved drug delivery and more effective treatment. The delivery of ciprofloxacin, and alkaloid drugs, particularly swainsonine, vincristine and vinblastine, is significantly improved.|
|Inventor(s):||Webb; Murray S. (Vancouver, CA), Bally; Marcel B. (Bowen Island, CA), Mayer; Lawrence D. (N. Vancouver, CA), Miller; James J. (Vancouver, CA), Tardi; Paul G. (Richmond, CA)|
|Assignee:||Inex Pharmaceuticals Corporation (CA)|
1. A liposome for delivery of an alkaloid therapeutic compound, produced by the process of:
forming a liposome from a mixture which comprises sphingomyelin and cholesterol, in a first buffered aqueous solution having an acidic pH greater than pH 2; and
suspending the liposome in a second buffered solution having a pH which is greater than that of the first buffered aqueous solution, whereby a transmembrane pH gradient is formed which facilitates the transfer of the therapeutic compound to the liposome.
2. The liposome produced by the process of claim 1, wherein the process further comprises the step of separating the liposome containing the therapeutic compound from the second buffer containing therapeutic compound which has not been entrapped by the liposome.
3. A liposome of claim 1, wherein the cholesterol is present in the liposomal composition at a total molar proportion of 30% to 50%.
4. A liposome of claim 1, wherein the sphingomyelin and cholesterol are present at a ratio of about 55/45, mol %/mol %, respectively.
5. A liposome of claim 1, wherein the alkaloid compound is vincristine or swainsonine.
6. A liposome of claim 1, wherein the alkaloid compound is vincristine.
7. A liposome of claim 1, wherein the alkaloid compound is swainsonine.
8. A liposome of claim 1, wherein the liposomes are unilamellar.
9. A liposome of claim 1, wherein the liposomes have mean diameters of about 0.05 microns to 0.45 microns.
10. A liposome of claim 1, wherein the liposomes have mean diameters of about 0.05 microns to 0.2 microns.
11. A liposome of claim 1, wherein the interior of said liposome is pH 2 to pH 5.
12. A liposome of claim 1, wherein the interior comprises a citrate buffer at about pH 4.0.
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