Bloodvesselofbrain endodermis cell target polylactic acid nanometer particle carrier, producing method and application thereof

A technology of cerebrovascular endothelium and nanoparticles, which is applied in the direction of extracellular fluid diseases, cardiovascular system diseases, blood diseases, etc., and can solve the problems of unresolved toxicity problems

Inactive Publication Date: 2008-06-18
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] PACA was once widely used in the research of drug carriers, but the emulsion polymerization method was used in the preparation process of PACA nanoparticles, which required a large amount of surfactants, and its LD 50 Only 20mg / kg, the toxicity problem has not been solved

Method used

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  • Bloodvesselofbrain endodermis cell target polylactic acid nanometer particle carrier, producing method and application thereof
  • Bloodvesselofbrain endodermis cell target polylactic acid nanometer particle carrier, producing method and application thereof
  • Bloodvesselofbrain endodermis cell target polylactic acid nanometer particle carrier, producing method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0116] Preparation of PLA nanoparticles:

[0117] Adopt nano-deposition method to prepare PLA nanoparticles, the preparation steps are as follows:

[0118] (1) Preparation of surfactant-free nanoparticles (blank nanoparticles, BNPs): PLA was dissolved in acetonitrile, and the resulting solution was slowly added to 50% (v / v) aqueous ethanol, and subsequently, the prepared suspension was Add it into distilled water while shaking, and then remove the organic solvent and part of the water with a rotary evaporator to prepare a BNPs suspension with a concentration of 1% (w / V);

[0119] (2) Preparation of fluorescently labeled PLA nanoparticles (FNPs): In order to facilitate the tracking of nanoparticles in animal experiments, FITC-Dextran (FITC-D) was added to the BNPs suspension, so that the weight of nanoparticles and FITC-Dextran The ratio was 10:1, and the FNPs suspension was prepared by standing for 24 hours;

[0120] (3) Preparation of T-80-modified PLA nanoparticles: T-80 w...

Embodiment 2

[0122] Preparation of PLA nanoparticles loaded with NF-κB decoy oligonucleotide fragments oligonucleotides, ODNs:

[0123] (1) Take an appropriate amount of NF-κB decoy ODNs aqueous solution, add 7.5% (wt / V) CTAB dropwise at a molar ratio of 1:1 to the base, and the obtained white flocs are subjected to high-speed centrifugation and freeze-drying to obtain ODNs - CTAB complex;

[0124] (2) Dissolving the ODNs-CTAB complex in dimethyl sulfoxide, and then into PLA, so that PLA:ODNs is 100:1 (mass ratio); then, under the condition of magnetic stirring, add 0.5-2.5% ( wt / V) of polyvinyl alcohol (PVA) aqueous solution, wherein the ratio of dimethyl sulfoxide solution to PVA aqueous solution is 1:4~1:6.6 (V / V), and then three times of high-speed centrifugation to remove dimethyl sulfoxide and PVA, add an appropriate amount of distilled water to obtain a suspension of ODNs nanoparticles loaded with NF-κB decoy (hereinafter referred to as ODNs-nanoparticles);

[0125] (3) ODNs-nanop...

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Abstract

The invention provides a polylactic-acid-nanometer-particle vector which can carry therapeutic gene fragments and induct the fragments directly to cerebral vascular endothelial cells. The invention, whose transfection efficiency is higher than the current vector, has the characteristics of tissue directionality and brain tissue accessibility. The invention, with good biological compatibility, is an ideal carrying tool. The invention simultaneously discloses a method for preparing PLA nanometer used for carrying NF- Kappa B decoy oligonucleotide fragments and the application in preparing the medicine for preventing cerebral thrombosis.

Description

technical field [0001] The present invention is a carrier and technology for introducing active substances for gene therapy into cerebrovascular endothelial cells, and is a multidisciplinary project involving biomedicine, material science, pharmacy and the like. Background technique [0002] As people's understanding of growth and disease mechanisms gradually penetrates to the molecular and gene levels, gene therapy is becoming an effective means to completely cure some diseases. Due to the special anatomical location of cerebrovascular diseases, common drugs are difficult to reach, and there is currently a lack of good treatment methods. Gene therapy is a new method that is expected to cure such diseases, but one of the difficulties facing gene therapy research is the lack of safe and cerebrovascular tissue-targeted gene carriers. Commonly used gene carriers, such as liposomes, have low transfection efficiency and cannot be applied to the treatment of cerebrovascular disea...

Claims

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Application Information

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IPC IPC(8): A61K47/34A61K48/00A61K9/107A61P7/02A61P9/10
Inventor 胡豫王华芳
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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