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Composite For Liver-Specific Delivery and Release of Therapeutic Nucleic Acids or Drugs

a nucleic acid or drug technology, applied in the field of compound for liver-specific delivery of a therapeutic nucleic acid or a drug, can solve the problem of limited tissue-specific targeting and other problems, and achieve the effect of improving the efficiency of the liver

Inactive Publication Date: 2008-06-12
MOGAM BIOTECH RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has merely been demonstrated in vitro, but not in vivo, that the cellular uptake of the HDL carrier by a hepatoma cell line, SMMC-7721, is higher in compared with a normal liver cell line, L02, and the limitation in tissue-specific targeting remains to be solved.

Method used

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  • Composite For Liver-Specific Delivery and Release of Therapeutic Nucleic Acids or Drugs
  • Composite For Liver-Specific Delivery and Release of Therapeutic Nucleic Acids or Drugs
  • Composite For Liver-Specific Delivery and Release of Therapeutic Nucleic Acids or Drugs

Examples

Experimental program
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Effect test

example 1

Preparation of the Inventive Composite

[0043]An equimolar mixture of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP; Avanti Polar Lipids, USA) and cholesterol (Sigma, USA) was dispersed in chloroform and mixed to form a cationic liposome of DOTAP / cholesterol (DTC). After the liposome assembly was formed, the organic solvent was removed by evaporation under a stream of N2 gas and the residue was kept in a vacuum desiccator for 2 hours to ensure the removal of the residual organic solvent. The resulting dried film was hydrated in a 5% dextrose solution and the suspension thus obtained was sonicated using a bath sonicator. A solution containing 10% the Apo A-I purified in Test Example 1 was added thereto at a DTC: Apo A-I mix ratio of 10:1 (w / w), and the mixture was kept overnight at 4° C. to obtain the inventive composite (DTC-Apo).

example 2

Preparation of the Inventive Composite Containing Nucleic Acid

[0044]40 μg of HBV X gene-specific siRNA (SEQ ID NOs: 1 (sense) and 2 (antisense); Shin, D., Virus Res. (2006), 119: 146-153) was mixed with 400 μg of the inventive composite, DTC-Apo, in 200 μl of 5% dextrose solution and the mixture was incubated at room temperature for 30 min, to obtain the inventive composite containing HBV X gene-specific siRNA, named DTC-Apo / siHBV.

example 3

Preparation of the Inventive Composite Containing Nucleic Acid

[0045]The procedure of Example 2 was repeated except for using firefly luciferase-specific siRNA (SEQ ID NOs: 3 (sense) and 4 (antisense); Elbashir, S. M., Nature (2001), 411: 494-498) instead of HBV-specific siRNA, to obtain the inventive composite containing firefly luciferase-specific siRNA, named DTC-Apo / siLuc.

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Abstract

The inventive composite having a nanoscale particle size can specifically deliver therapeutic nucleic acids or drugs to the liver and selectively release them into hepatic cells to manifest potent therapeutic effects without inducing any enzymatic abnormalities or pathological damage to the normal liver function, when administered together with the therapeutic agents.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a composite for liver-specific delivery of a therapeutic nucleic acid or a drug, a process for preparing the same and a composition comprising the same with a pharmaceutically acceptable carrier.BACKGROUND OF THE INVENTION[0002]A tissue-specific gene and drug delivery system has long been considered important for drug discovery and pharmaceutical advancement because most drugs are systemically delivered and circulated in the body when administered to a patient, which might adversely affect healthy organs or cells. The tissue-specific delivery system allows the accumulation of a high drug concentration at the target tissue which eliminating adverse side effects, leading to efficient treatment of tissue-specific diseases.[0003]Some liver diseases arise from infection by pathogenic viruses, e.g., HBV (hepatitis B virus) and HCV (hepatitis C virus), while non-infectious liver diseases result from exposure to liver-toxic materi...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/7088
CPCA61K31/7088A61K9/1272A61P31/12A61P31/18A61P31/20A61P35/00A61K38/17
Inventor KIM, MEEHYEINKIM, SOO INSHIN, DUCKHYANGPARK, MAHNHOON
Owner MOGAM BIOTECH RES INST
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