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Polycationic nucleic acid compound nano-particles as well as preparation method and application thereof

A nanoparticle and polycation technology, which is applied in the direction of drug combination, pharmaceutical formula, genetic material components, etc., to achieve the effect of inhibiting angiogenesis, avoiding adhesion, and improving the targeting effect

Inactive Publication Date: 2015-01-07
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0019] The purpose of the present invention is to provide a polycationic nucleic acid complex nanoparticle for the treatment of angiogenesis, so as to solve the above-mentioned technical problems existing in the existing anti-VEGF drugs for inhibiting angiogenesis
[0020] Another object of the present invention is to provide the above-mentioned preparation method of polycationic nucleic acid complex nanoparticles for treating angiogenesis, so as to solve the above-mentioned technical problems existing in the existing anti-VEGF drugs for inhibiting angiogenesis

Method used

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  • Polycationic nucleic acid compound nano-particles as well as preparation method and application thereof
  • Polycationic nucleic acid compound nano-particles as well as preparation method and application thereof
  • Polycationic nucleic acid compound nano-particles as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0047] The synthesis of embodiment 1 polycationic nucleic acid material (OPEI)

[0048] The synthetic route of polycationic nucleic acid material (OPEI) is as figure 1 shown. The whole reaction is carried out in an anhydrous and oxygen-free (high-purity nitrogen protection) environment, and the linear PEI 800Da and o-phthalaldehyde are reacted at a molar ratio of 1:2.5, and the reaction solvent is absolute ethanol (in anhydrous After adding anhydrous magnesium sulfate to ethanol, let stand for 48h, then distill to obtain fresh absolute ethanol for subsequent use). The infrared spectrum of PEI 800Da is as follows figure 2 shown. Dissolve PEI 800Da (1 mole) and o-phthalaldehyde (2.5 moles) in absolute ethanol to form 20 mL and 50 mL solutions, respectively. The reaction was carried out with stirring at room temperature, and the o-phthalaldehyde solution was added dropwise to the PEI 800Da solution using a constant pressure dropping funnel. Stop the reaction after 24 hours....

Embodiment 2

[0051] Example 2 Preparation of OPEI-encapsulated nanoparticles of plasmid DNA

[0052] The OPEI prepared in Example 1 was made into an aqueous solution with a concentration of 2 μg / μl, and diluted with sterilized water to form 20ng / μl, 40ng / μl, 100ng / μl, 200ng / μl, 1000ng / μl and 2000ng / μl solutions. In addition, the plasmid DNA containing 5'-GGAGUACCCUGAUGAGAUC-3' was made into an aqueous solution with a concentration of 20 ng / μl. Add an equal volume of the OPEI aqueous solution to the plasmid DNA aqueous solution, vortex for 5 minutes, and let stand for 20 minutes to obtain a series of nanoparticle solutions.

Embodiment 3

[0053] Example 3 Characterization of particle size and potential of nanoparticles

[0054] A series of particle solutions prepared in Example 2 are put into the test tank of the BIC90plus particle size potential analyzer, and the mass ratios of OPEI and plasmid DNA in the particles of the series of particle solutions are 1, 2, 5, 10, 50, 100, set The test temperature is 25°C, the medium is water, the viscosity is 0.89cp, the refractive index is 1.330, and the light scattering angle is 90°. , the detection wavelength is 659nm, each sample is tested 3 times, each run time is 2min, and the average particle size is recorded. Test results such as Figure 4 shown.

[0055] A series of particle solutions prepared in Example 2 are put into the test tank of the BIC90plus particle size potential analyzer, and the mass ratios of OPEI and plasmid DNA in the particles of the series of particle solutions are 1, 2, 5, 10, 50, 100, set The test temperature is 25°C, the medium is water, the...

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Abstract

The invention relates to the technical field of medicines for treating vascular proliferation and in particular relates to a polycationic nucleic acid compound for treating vascular proliferation as well as a preparation method and application thereof. According to the polycationic nucleic acid compound nano-particles for treating vascular proliferation disclosed by the invention, the nano-particles comprise polycationic nucleic acid materials and genetic substances, wherein a mass ratio of the polycationic nucleic acid materials to genetic substances is (1-100):1. The polycationic nucleic acid compound nano-particles for treating vascular proliferation comprise the polycationic nucleic acid materials and the genetic substances. Compared with the prior art, the nano-particles can effectively inhibit vascular proliferation and realize delivery of the genetic substances, and the problems of in-vivo toxicity and in-vivo immunogenicity are solved. Moreover, because the nano-particles are neutrally charged, adhesion of in-vivo non-target tissues can be avoided, and in-vivo pathological cell targeting is realized, so that the targeting effect is effectively improved, and endocytosis of in-vivo pathological cells is not influenced.

Description

technical field [0001] The invention relates to the technical field of drugs for treating vascular proliferation, in particular to a polycationic nucleic acid complex for treating vascular proliferation, its preparation method and application. Background technique [0002] Neovascularization can be accompanied by various conditions such as wound repair, tumor growth, and intraocular ischemic lesions. The formation of new blood vessels is a very complex biological process. A large number of current studies have shown that vascular endothelial growth factor (vascular endothelial growth factor, VEGF) and its family members can specifically promote the division, proliferation and migration of endothelial cells. important role in the formation process. [0003] VEGF is a kind of glycoprotein, which is widely distributed in brain, kidney, liver, spleen, lung, bone and other tissues in humans and animals. Human mature VEGF exists in five subtypes - VEGF121, VEGF145, VEGF165, VEGF...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/34A61K48/00C08J3/24A61P9/00A61P27/02C08L79/02
Inventor 袁伟恩陈顺车俊怡原明璐
Owner SHANGHAI JIAO TONG UNIV
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