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Nucleic acid drug carrier with mucus permeation as well as preparation method and application thereof

A nucleic acid drug and mucus penetration technology, which is applied in the field of nanomaterials and nanobiomedicine, can solve problems such as the complexity of the preparation process, and achieve the effects of simple preparation, strong mucus penetration, and enhanced penetration

Active Publication Date: 2022-01-18
CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above system has high requirements on material properties and design, and the preparation process is complicated.

Method used

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  • Nucleic acid drug carrier with mucus permeation as well as preparation method and application thereof
  • Nucleic acid drug carrier with mucus permeation as well as preparation method and application thereof
  • Nucleic acid drug carrier with mucus permeation as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Preparation of dopamine-functionalized hyaluronic acid

[0041] Accurately weigh 500 mg of hyaluronic acid (HA), dissolve it in 50 mL of PBS (pH 5.5) buffer solution, and add 1.3 mmol of dopamine hydrochloride (237.1 mg) and 1.3 mmol of EDC·HCl (240.0 mg) under vigorous stirring. Subsequently, the pH value of the mixture was adjusted to about 5.5 using 1M hydrochloric acid, and the stirring reaction was continued for 2 h under the protection of nitrogen. Finally, the resulting mixture was dialyzed with deionized water (MWCO=3500DA) for 24 hours, and finally vacuum freeze-dried to obtain an off-white powder, ie, dopamine-functionalized hyaluronic acid (HA-DA).

Embodiment 2

[0043] Preparation of poly-β-urethane

[0044] Accurately weigh 54.3mmol (5.0g) of glycerin and 162.9mmol (22.6mL) of triethylamine (TEA), and dissolve them in 60mL of dichloromethane, stir and cool to 5°C in an ice bath. Accurately weighed 168.3mmol (13.7mL) of acryloyl chloride, slowly dropped it into the above mixture under the protection of nitrogen, stirred in an ice bath for 30min, then warmed up to room temperature and reacted for 12h under stirring. Finally, the organic layer was washed three times with 100 mL of saturated sodium bicarbonate (NaHCO3) solution, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation to finally obtain a yellow oil. The crude product was purified by silica gel column chromatography (developing solvent: ether / ethyl acetate=10:1) to obtain glycerol triacrylate (GA).

[0045] Accurately weigh 1.0mmol (256.2mg) of the above synthetic GA, 25.2mmol (5.0g) of 1,4-butanediol diacrylate and 21.0mmol of 5-a...

Embodiment 3

[0047] Preparation of mucus-permeable nucleic acid drug carriers

[0048] Dissolve BP in sodium acetate buffer (0.02Mm, pH=5.5), dissolve siRNA in DEPC water, mix BP and siRNA according to the mass ratio of 30:1, vortex for 15s and incubate at room temperature for 30min to obtain BP / siRNA kernel. Then, the above-mentioned BP / siRNA cores were added into the HA-DA solution at different HA-DA / siRNA mass ratios, mixed upside down and left at room temperature for 30 minutes, and finally HA-DA / BP / siRNA NPs were obtained, in which HA-DA The mass ratios of BP and siRNA were 0:30:1, 1:30:1, 2.5:30:1, 5:30:1, and 10:30:1, respectively.

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Abstract

The invention provides a nucleic acid drug carrier with mucus permeation and a preparation method and application thereof. The nucleic acid drug carrier comprises a nucleic acid drug delivery inner core and a functionalization modification shell, the functionalization modification shell is a dopamine modified hyaluronic acid polymer, and the nucleic acid drug carrier has good mucus permeation capacity. The preparation method comprises the following steps: condensing a nucleic acid drug through a cationic polymer to form an inner core, and wrapping the inner core with a dopamine-modified hyaluronic acid polymer under physical interaction force to obtain the multifunctional nucleic acid drug nano-delivery carrier. According to the nano drug delivery carrier disclosed by the invention, the drug-carrying core is functionalized through a shell wrapping strategy, the mucus permeation ability of a nucleic acid drug is remarkably enhanced, target cell targeted delivery is realized, the nano drug delivery carrier can be used for gene therapy of lung diseases, and a new direction is provided for targeted therapy of the drug permeation mucus.

Description

technical field [0001] The invention relates to the fields of nanomaterials and nanobiomedicine, in particular to a mucus-permeable nucleic acid drug carrier and its preparation method and application. Background technique [0002] Pulmonary mucus is a highly viscous gel substance that mainly covers the interface between alveolar epithelial cells and air, and acts as a physical barrier to prevent foreign bodies from invading the human body. The mucus layer is formed by cross-linking a large number of mucin monomers containing densely glycosylated and negatively charged regions. It has a sieve-like structure with a pore size of 200-300 nm. Nanocomposites larger than 300 nm are difficult to pass through the sieve-like structure of the mucus layer. The positive charge on the surface of the material is also easily attracted by the negatively charged mucin in the mucus. Various reasons will affect the reach of the nanocomposite to the lesion. When a disease occurs, the excessive...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K31/7088A61K47/59A61K47/36A61P11/00
CPCA61K47/59A61K9/5161A61K31/7088A61P11/00
Inventor 周文虎朱皎皎
Owner CENT SOUTH UNIV
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