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Radiation sensitive liposomes

a liposome and liposome technology, applied in the field of radiation sensitive liposomes, can solve the problems of slow passive leakage of encapsulated chemotherapeutics, can significantly affect the cells at the site, and can localize the destruction of target cells, and achieve the effect of enhancing the release of encapsulated water soluble molecules

Inactive Publication Date: 2006-05-11
VARIAN MEDICAL SYSTEMS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to liposomes that are sensitive to radiation and can be used for diagnostic and therapeutic purposes. The liposomes contain a polymerizable colipid that polymerizes upon exposure to ionizing radiation, resulting in the destabilization of the liposomal membrane and leakage of liposomal contents. The use of radiation to release liposomal contents is efficient and convenient, as it can be integrated into currently available radiation-based clinical methods. The radiation-sensitive liposomes can be used for diagnostic and therapeutic purposes, such as cancer treatment. The invention also provides methods for producing the radiation-sensitive liposomes and methods for attaching poly(ethylene glycol) to lipid(s) in the liposomes.

Problems solved by technology

However, it has been shown that once sterically stabilized liposomes have accumulated at tumor sites the slow passive leakage of encapsulated chemotherapeutics, e.g., doxorubicin, can significantly affect the cells at that site.
Hence, the photodynamic effect results in the localized destruction of the target cells.
However, while the use of ionizing radiation to initiate chain polymerizations is known in the art, less is known about the effects of ionizing radiation in order to stabilize lipid bilayer membranes composed of polymerizable lipids.
However, while the use of ionizing radiation to stabilize lipid bilayer membranes composed of polymerizable lipids is known, there are no reports about the use of ionizing radiation for the purpose of liposome destabilization.
UV light can only be used where the target tissue is superficially accessible to the light source.

Method used

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Embodiment Construction

[0037] a) Definitions and General Parameters

[0038] The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein.

[0039] The term “liposome” refers to a microscopic vesicle comprising lipid bilayer(s). Structurally, liposomes range in size and shape from long tubes to spheres and are normally 100±10 nm in diameter, but can be as small as 25 nm and as large as 500 nm in diameter. Liposomes may contain one or more bilayer(s). Agents or molecules can be incorporated into the liposome. For example, molecules may be encapsulated in or associated with the liposome. A liposome with such encapsulated or associated agents (e.g., therapeutic or diagnostic agents) may be targeted to specific site(s) (e.g., tissue of interest such as a tumor tissue) and its contents released when appropriate. Liposomes may also be targeted to specific site(s) in vitro or in vivo through attached targeting sequences such as pept...

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Abstract

The present invention relates to a radiation sensitive liposome, and the use of this liposome as carrier for therapeutic and diagnostic agent(s). In particular, the invention encompasses a liposomal delivery system, comprising a stable liposome-forming lipid and a polymerizable colipid, a fraction of which polymerizable colipid polymerizes upon exposure to ionizing, radiation, thereby destabilizing the liposomal membrane. Destabilization of liposomes allows for leakage of liposomal contents. The present invention further contemplates methods of diagnosing and treating conditions and diseases that are responsive to liposome-encapsulated or associated agents.

Description

BACKGROUND OF THE INVENTION [0001] a) Field of the Invention [0002] The present invention relates to radiation sensitive liposomes and the use of these liposomes as carriers for therapeutic and diagnostic agents. The invention further relates to methods of producing the radiation sensitive liposomes and to methods of diagnosing and treating cancer and other conditions and diseases. [0003] b) Description of Related Art [0004] Liposomes are microscopic vesicles consisting of concentric lipid bilayers. Structurally, liposomes range in size and shape from long tubes to spheres, with dimensions from a few hundred Angstroms to fractions of a millimeter. Regardless of the overall shape, the bilayers are generally organized as closed concentric lamellae, with an aqueous layer separating each lamella from its neighbor. Vesicle size normally falls in a range of between about 20 and about 30,000 nm in diameter. The liquid film between lamellae is usually between about 3 and 10 nm. A variety of...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K51/00A61K9/127A61K9/00A61K45/00A61K47/34A61K47/42A61K47/44A61N5/10
CPCA61K9/0009A61K9/1273A61P25/00A61P35/00A61P37/00
Inventor O'BRIEN, DAVID F.MCGOVERN, KATHY A.BONDURANT, BRUCESUTHERLAND, ROBERT
Owner VARIAN MEDICAL SYSTEMS
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