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Solid-phase-core coating recombinant lipoprotein, preparation and applications thereof

A technology of solid-phase core and apolipoprotein, which is applied in the direction of non-active ingredient medical preparations, active ingredient-containing medical preparations, drug combinations, etc., and can solve the problem of limited loading method, physical and chemical properties of drug molecules, low loading capacity, etc. problems, to achieve the effect of improving load capacity and stability, and not easy to gather

Active Publication Date: 2018-08-28
SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although lipoproteins have been successfully used to load various drugs, the loading capacity is low, and the loading method is largely limited by the physicochemical properties of drug molecules.

Method used

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  • Solid-phase-core coating recombinant lipoprotein, preparation and applications thereof
  • Solid-phase-core coating recombinant lipoprotein, preparation and applications thereof
  • Solid-phase-core coating recombinant lipoprotein, preparation and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1. Preparation and Characterization of Recombinant Lipoprotein Containing Calcium Phosphate Solid Phase Core

[0047] (1) Preparation

[0048] The calcium phosphate solid-phase inner core is prepared by a reverse microemulsion method, and the reverse microemulsion is prepared by dispersing an aqueous solution into a cyclohexane oil phase solution containing nonylphenol polyoxyethylene ether. First, 300 μL of 2.5 M CaCl 2 The solution is dispersed in 20mL oil phase to form a uniformly dispersed water-in-oil reverse microemulsion, and this step is the preparation of the calcium phase. The phosphorus phase was prepared by dissolving 300 μL of 12.5 mM Na 2 HPO 4 The solution was dispersed in another 20 mL oil phase, and after stirring for 10 min, 100 μL of 20 mg / mL 1,2-dioleoyl phosphatidic acid (DOPA) solution was added to the phosphorus phase. After the two phases were evenly dispersed, the two phases were mixed and stirred for 45 min. After the microemulsion...

Embodiment 2

[0053] Example 2. Preparation of recombinant lipoprotein containing calcium carbonate solid phase core

[0054] The calcium carbonate solid-phase core is prepared by a reverse microemulsion method, and the reverse microemulsion is prepared by dispersing an aqueous solution into a cyclohexane oil phase solution containing nonylphenol polyoxyethylene ether. First add a small amount of CaCl 2 The solution is dispersed in the oil phase to form a uniformly dispersed water-in-oil inverse microemulsion, and this step is the preparation of the calcium phase. The carbon phase is prepared by Na 2 CO 3 The solution was dispersed in another oil phase, and after stirring for 10 min, 100 μL of 20 mg / mL 1,2-dioleoylphosphatidic acid (DOPA) solution was added to the carbon phase. After the two phases were evenly dispersed, the two phases were mixed and stirred for 45 min. After the microemulsions react after exchange, calcium carbonate precipitation will be produced. At this time, 40 mL ...

Embodiment 3

[0056] Example 3. Incubate the recombinant lipoprotein of the calcium phosphate solid-phase inner core of NC siRNA or ordinary liposomes, and co-incubate with 10% FBS, evaluate the stability of the recombinant lipoprotein of the NC siRNA calcium phosphate solid-phase inner core

[0057] (1) Preparation

[0058] The calcium phosphate solid-phase inner core is prepared by the inverse microemulsion method as in Example 1. First, 300 μL of CaCl with a concentration of 2.5M 2 The solution was mixed with 80 μL of 2 mg / mL NC siRNA solution and then dispersed in 20 mL of oil phase to form a uniformly dispersed water-in-oil inverse microemulsion. This step was the preparation of the calcium phase. The subsequent preparation method was the same as that in Example 1. The calcium phosphate solid-phase core loaded with NC siRNA and DOPA was prepared, dispersed in 1 mL of chloroform and stored in a glass bottle for subsequent experiments.

[0059] Prepare ordinary liposomes containing calc...

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Abstract

The invention discloses a lipoprotein nanometer drug delivery system containing a solid phase core, and a preparation method thereof, and applications of the lipoprotein nanometer drug delivery systemin preparation of drugs. According to the present invention, the drug-loading solid phase core is coated with the recombinant lipoprotein, such that the limitation that the drug coating method is limited by the physical and chemical properties of the drug is solved, and the loading ability and the stability of the hydrophilic drug are improved; the nanometer drug delivery system has performancesof lysosome escape, high Ras expression or activated tumor cell targeting property, blood-brain barrier permeability and the like; and the preparation method is simple, and is suitable for large-scaleproduction.

Description

technical field [0001] The invention relates to the fields of biotechnology and chemical pharmacy, relates to a drug delivery system, in particular to a recombinant lipoprotein containing a solid-phase inner core, a preparation method thereof, and an application thereof in preparing medicine. Background technique [0002] In recent years, the research on gene therapy has been paid more and more attention. For example, the research on RNAi is a new type of tumor treatment strategy developed in recent years. Since the use of RNAi technology can specifically eliminate or turn off the expression of specific genes, this technology has been widely used In the field of exploring gene function and gene therapy of malignant tumors. However, how to efficiently target and deliver complete and functional gene drugs is still the main rate-limiting step in the application of gene therapy for tumors and other diseases, that is, how to efficiently target and deliver gene drugs to tumor tiss...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/24A61K47/28A61K47/14A61K47/18A61K47/02A61K31/7105A61K48/00A61P35/00A61P25/00
CPCA61K9/5115A61K9/5123A61K9/5169A61K31/7105
Inventor 高小玲黄佳琳江淦宋清香陈红专
Owner SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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