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Cationic liposome, and preparation method and application thereof

A cationic liposome and carrier technology, which is applied to other methods of inserting foreign genetic materials, pharmaceutical formulas, genetic material components, etc., can solve the problems of low transfection efficiency, achieve optimized preparation parameters, improve transfection efficiency, and use Dose Reduction Effects

Inactive Publication Date: 2014-07-23
HUAQIAO UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the disadvantage is that its transfection efficiency is still lower than that of viral gene vectors, so it is necessary to develop new liposomes with better safety and transfection activity, and use cationic liposomes to co-carry genes and chemotherapeutic drugs for combined treatment to play a more effective role. good therapeutic effect

Method used

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  • Cationic liposome, and preparation method and application thereof
  • Cationic liposome, and preparation method and application thereof
  • Cationic liposome, and preparation method and application thereof

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preparation example Construction

[0049] The present invention also relates to a preparation method of cationic liposome, comprising the following steps:

[0050] Step 10, take 1 weight part of DOPE, 1 weight part of DC-Chol, and 2.5 weight parts of OQCMC according to the proportion and dissolve them in the chloroform solvent;

[0051] Step 11, mix the solution obtained in step 10, add ultrapure water for blending, and sonicate the probe for 10 minutes;

[0052] Step 12, remove the residual solvent of the product obtained in step 11 in a rotary evaporator, and obtain it in a vacuum state; the evaporation temperature of the rotary evaporator is 35°C.

[0053] The present invention also relates to a cationic liposome complex. The cationic liposome complex uses cationic liposome as an encapsulation layer, and a drug carrier, a gene carrier, or a gene and a drug are co-loaded in the encapsulation layer. At least one of the carriers; the cationic liposome is prepared from the following components in parts by weigh...

Embodiment 1

[0061] Embodiment one cationic liposome formula of the present invention and preparation technology are preferred

[0062] Cationic liposomes were selected as the target liposome type, and after preliminary screening tests, octadecyl quaternary ammonium carboxymethyl chitosan (OQCMC), dioleoylphosphatidylethanolamine (DOPE) and 3-β-N-N '-N'-Dimethylaminoethyl-carbamoylcholesterol (DC-Chol), as the base ingredient, was then optimized for formulation.

[0063] The cationic liposome preparation method of the present invention and the amount of CLP and siRNA are optimized according to a certain ratio, as shown in Table 1 (the particle size and potential change of the complex caused by the mass ratio of the two): CLP-siRNA increases in size with the increase of siRNA mass. The size and charging conditions change, showing that the particle size increases continuously, while the potential decreases continuously. This indirectly shows that siRNA and CLP have an electrostatic binding ...

Embodiment 2

[0066] The preparation of embodiment two cationic liposome CLP of the present invention

[0067] Weigh 2.5 parts by weight of OQCMC, 1 part by weight of DOPE, and 1 part by weight of DC-Chol, and dissolve them in chloroform; The residual chloroform was removed by an instrument to obtain OQCMC-CLP (abbreviated as CLP) and CLP-PTX with a concentration of 2.67 mg / mL (V / W). The samples were sealed, protected from light, and stored at a low temperature of 4°C for later use.

[0068] The physical and chemical properties of the prepared cationic liposomes were characterized by infrared spectroscopy (FTIR), Malvern particle size analyzer, TEM, and AFM for blank CLP and CLP complexes. Its infrared spectrum is as figure 1 As shown, CLP was successfully prepared from DC-Chol, DOPE and OQCMC. In the DC-Chol-DOP spectrum, at 1050cm -1 A new absorption peak (-P=O-group) appeared at , which corresponds to the carboxyl group of DOPE, proving that DOPE was attached to DC-Chol. At the same...

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Abstract

The invention provides a cationic liposome, and a preparation method and application thereof. The cationic liposome is prepared from the following components in parts by weight by adopting a reverse evaporation method: 1 part of DOPE (dioleoyl phosphatidyl ethanolamine), 1 part of DC-Chol and 2.5 parts of OQCMC (octadecyl quaternized carboxymethyl chitosan). A cationic liposome complex adopts the cationic liposome as an encapsulating layer, wherein at least one of a medicinal carrier, a gene carrier or a gene-medicine co-carrier is encapsulated in the encapsulating layer. The liposome component is close to the cytomembrane component, the cationic liposome has better biodegradability, better biocompatibility, low immunity and low cell toxicity; the liposome is an amphoteric matter, so that the liposome can be used for encapsulating polar chemotherapeutic drugs or non-polar chemotherapeutic drugs or simultaneously encapsulating polar and non-polar drugs.

Description

【Technical field】 [0001] The invention relates to a cationic liposome and its preparation method and application. 【Background technique】 [0002] Non-viral gene vectors are currently one of the most potential vectors in gene therapy, especially cationic liposomes. It has the advantages of good source and biocompatibility, and can load foreign gene fragments up to 52kb in size. At present, the carrier has become one of the research hotspots of gene therapy. [0003] Although at present cationic liposomes are mainly due to the higher charge, they can cause cytoplasmic shrinkage, inhibit normal cell division, inhibit protein kinase activity, and generate vacuoles in the cytoplasm. Modification or addition of negative polymers, colipids, and finding the best N / P can obtain cationic liposomes with high transfection efficiency, high targeting, and low cytotoxicity. It has been used more and more clinically. Among them, the cationic liposome DMRIE / DOPE is used as the gene carri...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P35/00C12N15/87
Inventor 王士斌陈伟光陈爱政刘源岗吴文果
Owner HUAQIAO UNIVERSITY
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