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Preparation method of mediated-heparin intracellular delivery crosslinking nanometer carrier

A nanocarrier, heparin technology, applied in the field of biomedicine, can solve problems such as degradation and entry into cells

Inactive Publication Date: 2015-04-22
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the anti-tumor effect of heparin shows a good application prospect, it is difficult to enter the cell through the negatively charged cell membrane due to the large amount of negative charge on the surface of the heparin molecule, and it is easy to bind to the protein in the plasma, and it is easy to be degraded by heparinase on the cell surface

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0010] Example 1: Preparation of PEG-COOH

[0011] Measure a certain amount of acetonitrile, add 0.5-1% P2O5, azeotropically reflux at 82°C for 8 hours, obtain anhydrous acetonitrile by fractional distillation, soak in 4A molecular sieves for later use; pyridine and a certain amount of NaOH azeotropically reflux at 116°C After 12 hours, anhydrous pyridine was obtained by fractional distillation, which was soaked in 4A molecular sieves for use. Weigh 10g of PEG and dissolve in 20mL of anhydrous acetonitrile, add 3g of succinic anhydride and 15mL of anhydrous pyridine, stir overnight at room temperature, remove the acetonitrile and pyridine by rotary evaporation, drop the remaining colorless transparent viscous liquid into 150mL of anhydrous diethyl ether and stir vigorously, A white precipitate was produced, and the solid obtained by suction filtration was repeatedly washed with anhydrous ether 3 times, and finally the white solid obtained by suction filtration was recrystalliz...

Embodiment 2

[0012] Embodiment two: the preparation of PEG-PEI block copolymer

[0013] Weigh 0.2g PEG-COOH and dissolve it in 10mL deionized water, adjust the pH value to between 4.5 and 6, add 0.077g EDC·HCl and stir to dissolve; weigh 0.432g PEI and dissolve it in 10mL deionized water, slowly drop the PEI solution Add to the solution of PEG-COOH, vortex and shake while adding dropwise, stir at room temperature for 24 hours, dialyze in deionized water with MWCO 1000Da dialysis bag for 3 days, remove small molecular impurities, freeze-dry to obtain PEG-PEI copolymer . The formation of the product was detected by nuclear magnetic resonance and infrared spectroscopy, and the infrared was at 1103 cm -1 There is a strong absorption peak at , here is the absorption peak of C-O-C; 1471cm -1 The stretching vibration absorption peak of C-N is at 1628cm -1 The place is the absorption peak of amide I with C=O, 2949cm -1 at -CH 2 The absorption peak of -, 3369cm -1 The place is the absorption ...

Embodiment 3

[0014] Example 3: Preparation and crosslinking of PEG-PEI / Heparin nanocomposite

[0015] Weigh 40mg PEG-PEI and 40mg heparin sodium and dissolve in 4mL deionized water respectively. Take a certain amount of heparin sodium solution, slowly drop it into a certain amount of PEG-PEI solution, shake it while adding it, shake it for 5-10 minutes immediately after the dropwise addition, and let it stand for 30 minutes. Prepare PEG-PEI:Hep composites with weight ratios (w / w) of 0.4, 0.6, 0.8, 1, 2, and 5 respectively according to the above method, and control the final concentration of heparin sodium to 0.5 mg / mL. On this basis, add an appropriate amount of DMSO solution of cross-linking agent DSP (the amount of DMSO is less than 5%), mix evenly with a pipette tip, and place it for 30 minutes to make the cross-linking reaction fully proceed, and obtain cross-linked PEG-PEI / Heparin nano Complex. The particle size and distribution of the cross-linked nanocomposites and the Zeta-potent...

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PUM

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a preparation method of a mediated-heparin intracellular delivery crosslinking nanometer carrier. PEG-modified PEI is adopted; and heparin is entrapped by using cation performance of PET, so that the cell endocytosis ability is increased; the water solubility, the stability and the blood metabolic capability of a carrier and nano composites are improved by PEG molecules; removal of combination of composites and protein is avoided; meanwhile, degradation of the heparin caused by heparin enzyme action is avoided; in addition, effective release of the heparin in cells is achieved; and a disulfide bond is introduced through a crosslinking agent on the basis, so that nanoparticles are degraded to release the heparin, thus the heparin plays a biological effect in the cells.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a preparation method of a cross-linked nano-carrier mediating intracellular transmission of heparin. Background technique [0002] As an anticoagulant drug widely used clinically, heparin has a history of more than 60 years. Its anticoagulant activity is mainly through the binding of antithrombin (AT-III) through its pentose active center, and inducing its conformational transformation, thereby activating AT-III, and AT-III further binds and inhibits a variety of coagulation chain reactions. Thrombin (including coagulation factors Xa and IIa, etc.), thus showing anticoagulant activity. In addition to the classic anticoagulation and related antithrombotic activities, heparin also has various biological activities such as anti-smooth muscle cell proliferation, anti-inflammation, anti-tumor and anti-virus, and these biological activities are closely related to the special mol...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/727A61P35/00
Inventor 滕丽萍付海田王敏陈敬华
Owner JIANGNAN UNIV
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