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Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes

a technology of cisplatin and other drugs, applied in the direction of drug compositions, genetic material ingredients, peptide/protein ingredients, etc., can solve the problems of limited therapeutic efficacy, limited therapeutic efficiency, and no synthesized compound showed significant cytotoxic activity against three, so as to improve the entrance across the cell membrane, high therapeutic efficacy, and high yield

Inactive Publication Date: 2009-11-12
REGULON INC
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Problems solved by technology

However, none of the synthesized compounds showed any significant cytotoxic activity against three cell lines that were treated (Kim et al., 1998).
Thus, while the prior reports indicate that liposome mediated delivery of cisplatin and other therapeutic drugs is possible, therapeutic efficiency has been limited by the low aqueous solubility and low stability of cisplatin.
Therapeutic efficacy also is limited by the high toxicity of the drug.

Method used

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  • Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes
  • Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes
  • Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes

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Preparation of Micelles and Lipid-Encapsulated Cisplatin

[0100]One formula for encapsulation includes the steps of: (A) mixing cisplatin (in powder or other form) with DPPG (dipalmitoyl phosphatidyl glycerol) or other negatively-charged lipid molecules at a 1:1 to 1:2 molar ratio in at least a 30% ethanol, 0.1 M Tris HCl, pH 7.5 to achieve about 5 mg / ml final cisplatin concentration. Variations in the molar ratio between cisplatin and DPPG are also of therapeutic value targeting different tissues. (B) Heating at 50 .degree. C.

[0101]During steps A and B the initial powder suspension, which tends to give a precipitate of the yellow cisplatin powder, is converted into a gel (colloidal) form; during steps A and B there is conversion of cisplatin to its aqua form (by hydrolysis of the chloride atoms and their replacement by water molecules bound to the platin) which is positively-charged and is the active form of cisplatin endowed with the antineoplastic activity; the aqua cisplatin is si...

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Abstract

A method for encapsulating cisplatin and other positively-charged drugs into liposomes having a different lipid composition between their inner and outer membrane bilayers is disclosed. The liposomes are able to reach primary tumors and their metastases after intravenous injection to animals and humans. The encapsulated cisplatin has a high therapeutic efficacy in eradicating a variety of solid human tumors including but not limited to breast carcinoma and prostate carcinoma. Combination of the encapsulated cisplatin with encapsulated doxorubicin or with other antineoplastic drugs are claimed to be of therapeutic value. Also of therapeutic value in cancer eradication are claimed to be combinations of encapsulated cisplatin with a number of anticancer genes including but not limited to p53, IL-2, IL-12, angiostatin, and oncostatin encapsulated into liposomes as well as combinations of encapsulated cisplatin with HSV-tk plus encapsulated ganciclovir.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit under 35 U.S.C. § 120 of U.S. Ser. No. 09 / 434,345, filed Nov. 5, 2000, now U.S. Pat. No. ______, issued ______, the contents of which are hereby incorporated by referenced into the present disclosure.FIELD OF THE INVENTION[0002]The present invention relates to liposome encapsulated drugs and delivery systems, specifically liposome encapsulated cisplatin. The drugs are useful to kill cancer cells in a variety of human malignancies after intravenous injection.BACKGROUND OF THE INVENTION[0003]Throughout this application various publications, patents and published patent specifications are referenced by author and date or by an identifying patent number. Full bibliographic citations for the publications are provided within this disclosure or immediately preceding the claims. The disclosures of these publications, patents and published patent specifications are hereby incorporated by reference into the prese...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/127A61K33/24A61K38/20A61K38/21A61K9/107A61K31/282A61K31/337A61K31/437A61K31/522A61K31/573A61K31/704A61K31/7064A61K31/7072A61K33/243A61K45/00A61K45/06A61K47/28A61K47/34A61K47/42A61K47/48A61K48/00A61P35/00C12N15/88
CPCA61K9/1075A61K9/127A61K31/7072A61K31/704A61K31/573A61K31/475A61K31/337A61K38/14A61K38/00C12N15/88A61K48/00A61K47/488A61K45/06A61K33/24A61K9/1278A61K9/1271A61K2300/00A61K47/6907A61P35/00A61P35/04A61K33/243
Inventor BOULIKAS, TENI
Owner REGULON INC
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