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Apoptosis-Modulating Protein Therapy for Proliferative Disorders and Nanoparticles Containing the Same

Inactive Publication Date: 2009-01-15
BOARD OF RGT UNIV OF NEBRASKA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016]In yet another embodiment, a method of inhibiting inflammation in a patient following angioplasty is provided comprising administering to said

Problems solved by technology

Repeated delivery of the vector may cause toxicity, including an inflammatory response and the therapy may not be effective (Maheshwari, A. et al.
It has been also suggested the loss of p53 function also affects the efficacy of anti-cancer drugs.
Increased formation of RS can promote the development of malignancy, and the ‘normal’ rates of RS generation may account for the increased risk of cancer development in the aged.
For example, it is difficult to ensure that enough p53 nucleic acid enters the cell to be subsequently encoded into sufficient levels of functional p53 protein to ameliorate the symptoms of proliferative disease.
Additionally, it is unclear whether diseased cells are capable of transcribing and producing protein in an efficient manner.

Method used

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  • Apoptosis-Modulating Protein Therapy for Proliferative Disorders and Nanoparticles Containing the Same
  • Apoptosis-Modulating Protein Therapy for Proliferative Disorders and Nanoparticles Containing the Same
  • Apoptosis-Modulating Protein Therapy for Proliferative Disorders and Nanoparticles Containing the Same

Examples

Experimental program
Comparison scheme
Effect test

example i

Sustained Release of p53 Protein From Nanoparticles

[0074]A western blot was performed to assess p53 release from the nanoparticle formulation (FIG. 3). The western blot analysis of p53 protein release from NPs demonstrated robust bands corresponding to the p53 protein band prior to its encapsulation. This confirms that the protein maintained its configuration following its encapsulating into the NPs, and also when it is released slowly from NPs.

example ii

Balloon Injury and Inhibition Restenosis With p53 Protein-Loaded NP in a Rat Carotid Artery Model

[0075]The preliminary study in rat carotid artery model demonstrated significant inhibition of restenosis with a single-dose localized administration of p53 protein-loaded NPs (dose of protein=1.6 microgram). After balloon injury, NP suspension in saline was infused over 5 minutes at 2 atm of pressure (three 1-min periods between infusions of 70 μl of the suspension, with a 1 min period between infusions). The control group contained NPs without p53 protein. After three weeks, infused arteries were isolated, sectioned every 3 mm from the proximal to the distal ends, and were analyzed for proliferation. See FIGS. 4A-4D. The data demonstrate that p53 protein in modified NPs is effective in inhibiting restenosis. There is significant inhibition of intima to media ratio (65% inhibition of restenosis), and a corresponding increase in the lumen diameter in the p53 protein treated animals as co...

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Abstract

Protein containing nanoparticles and methods of use thereof for the treatment of proliferative disorders are disclosed.

Description

[0001]This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application, 60 / 958,830 filed Jul. 9, 2007, the entire content of which is incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to the fields of drug delivery and proliferative disorders. More specifically, the invention provides p53 protein containing nanoparticles and methods of use thereof for the treatment of diseases associated with aberrant p53 functions, including without limitation, restenosis, tumor growth, for modulating drug effects which are dependent on p53 functional activity (e.g., drug resistance in cancer therapy), and altered artherogenesis.BACKGROUND OF THE INVENTION[0003]Several references and patent documents are cited throughout this application to better define the state of the art to which the invention pertains. Each of these citations is incorporated by reference herein as though set forth in full.[0004]Gene delivery using non-viral syste...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P9/00A61P29/00
CPCA61K38/1709A61K38/1761A61K2300/00A61P29/00A61P9/00A61P9/14
Inventor LABHASETWAR, VINOD
Owner BOARD OF RGT UNIV OF NEBRASKA
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