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Components of macrophage targeting carrier system, preparation method of macrophage targeting carrier system and application of macrophage targeting carrier system to medicines and nucleic acid delivery

A technology for targeting macrophages and drugs, which is applied in the field of components of macrophage targeting carrier systems, and can solve the problems of high cytotoxicity, ineffective macrophages, and low gene transfection efficiency.

Pending Publication Date: 2021-10-29
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these methods often have low gene transfection efficiency or high cytotoxicity
In addition, non-viral vectors based on cationic lipids and polymers, such as liposomes and poly(β-amino Phage cells are not efficient gene transfection vehicles

Method used

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  • Components of macrophage targeting carrier system, preparation method of macrophage targeting carrier system and application of macrophage targeting carrier system to medicines and nucleic acid delivery
  • Components of macrophage targeting carrier system, preparation method of macrophage targeting carrier system and application of macrophage targeting carrier system to medicines and nucleic acid delivery
  • Components of macrophage targeting carrier system, preparation method of macrophage targeting carrier system and application of macrophage targeting carrier system to medicines and nucleic acid delivery

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preparation example Construction

[0162] The preparation method of the nanoparticle of the present invention mainly includes steps: (1) preparation of the nanoparticle unit in the compound and (2) mixing of the nanoparticle unit to obtain the nanoparticle of the present invention.

[0163] Wherein, the preparation method of the nanoparticle unit can be prepared by methods well known to those skilled in the art.

[0164] Preferably, in step (2), mixing is performed in the presence of a stabilizer. Wherein, the stabilizer is selected from the group consisting of polyvinyl alcohol, polyglycerin fatty acid ester, Tween 80, Tween 20, Span80, Span60, sodium dodecylsulfonate, or a combination thereof. Preferably, the stabilizer is used at a concentration of 0.1wt%-10wt%.

[0165] In another preferred example, the method further includes step (iii): separating the nanoparticles, including removing the stabilizer.

[0166] In a preferred embodiment, the nanoparticle units can be compounded by a precipitation method t...

Embodiment 1

[0248] Example 1: Synthesis and Characterization of Carbohydrate-Conjugated PLGA or PLGA-PEG Polymers

[0249] Such as figure 1 As shown in A, we use PD's 1 Peak c (4.49ppm, dextran terminal proton) and peak a (5.21ppm, -OCH(CH) in the H NMR spectrum 3 )CONH-) to assess the number of PLGA chains in each dextran. The number of PLGA chains grafted to dextran can be controlled by adjusting the feed molar ratio (γ), when PLGA / D-70-NH 2 When the γ was 18.4, the average number of PLGA chains grafted per dextran was 20. The GPC trace of PD showed no residual unreacted PLGA, and the polymer had a low polydispersity (ηfigure 1 D). PPM and PPG polymers were synthesized in a similar manner, sequentially undergoing acylation, amine deprotection, and acylation reactions (Scheme 2&3). The first step, by calculating the phenyl protons (7.5, 7.0ppm) and tert-butyl protons (1.37ppm, -C(CH 3 ) 3 ), the reaction rate of grafting mannose or galactose to PEG was 100% (Fig. S4&S5). In the s...

Embodiment 2

[0250] Embodiment 2: Preparation and characterization of NPs

[0251] Using carbohydrate-modified polymers, we designed and prepared a series of NPs by nanoprecipitation method ( figure 2 A). Briefly, the polymer was dissolved in an organic solvent and added dropwise to deionized water. Two kinds of NPs were formulated, including NPs of the same composition (i.e., PPM, PPG, and PD) and PPM / G NPs composed of a mixture of PPM and PPG at a weight ratio of 1:1. In addition, during the formulation process, Cy5.5-labeled PLGA-PEG (PP-Cy5.5) was incorporated into NPs for subsequent flow cytometry detection of phagocytosis of NPs by macrophages. The average hydrodynamic size of the resulting NPs was measured using dynamic light scattering (DLS). We found that the particle size depends on the type of organic solvent used and the polymer concentration. The particle size was larger when NPs were formulated with acetone compared to DMSO, and increased polymer concentration also resul...

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Abstract

The invention provides a macrophage targeting carrier system. Specifically, the invention provides a macrophage targeting nano-particle carrier system, components of the nano-particle carrier system, a preparation method of the nano-particle carrier system and an application of the nano-particle carrier system to the aspects of medicines and nucleic acid delivery. The main body material of the nano-particles provided by the invention has biodegradability, biocompatibility and delayed slow release property, and can be injected locally or wholly. Moreover, the synthesis method is simple, convenient and efficient, the surfaces of the prepared nano-particles contain high-density targeting elements, and the medicines and genes can be efficiently delivered to macrophages in a targeted mode. The nano-particles rich in targeting elements and the developing agents can be specifically enriched in macrophages and are used for diagnosis and treatment of diseases.

Description

technical field [0001] The invention belongs to the field of medical materials, and in particular relates to the components of a macrophage targeting carrier system, its preparation method and its application in drug and nucleic acid delivery. Background technique [0002] Macrophages are important cells in the innate immune system and play critical roles in tissue homeostasis and immunity. But they can also contribute to a variety of pathological processes, including autoimmune diseases, cancer, infectious diseases, and inflammatory diseases. [0003] In general, macrophages have two important subpopulations: "classically activated macrophages" (M1) and "selectively activated macrophages" (M2), which are present in the inflammatory environment of various diseases , such as solid tumors, type II diabetes and atherosclerosis. M1s and M2s are thought to be responsible for distinct functions in these microenvironments. For example, in the tumor microenvironment, M2s macropha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K47/26A61K47/36A61K9/14A61K48/00A61K49/00A61K49/12A61K49/10A61K49/18A61K51/04A61K51/06A61K51/12A61P3/10A61P3/04A61P35/00A61P11/00A61P9/00A61P29/00C12N15/87
CPCA61K9/145A61K9/146A61K48/0041A61K48/0033A61K49/0054A61K49/0052A61K49/0093A61K49/126A61K49/10A61K49/1845A61K49/1857A61K49/186A61K49/1863A61K51/0491A61K51/06A61K51/1244A61K49/00A61P3/10A61P3/04A61P35/00A61P11/00A61P9/00A61P29/00C12N15/87
Inventor 章雪晴陈起静高明珠
Owner SHANGHAI JIAO TONG UNIV
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