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Metal organic framework nanoparticles for oral protein administration and preparation method of metal organic framework nanoparticles

A metal-organic framework and nanoparticle technology, applied in the field of pharmacy, can solve the problems of low protein oral bioavailability and complex product preparation process, and achieve good biocompatibility, slow and controlled release kinetics, low price, and convenient protein The effect of oral administration

Pending Publication Date: 2022-04-15
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to overcome the disadvantages and deficiencies of the prior art, such as low protein oral bioavailability and complex product preparation process, and provide a metal-organic framework nanoparticle for oral protein administration and its preparation method

Method used

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  • Metal organic framework nanoparticles for oral protein administration and preparation method of metal organic framework nanoparticles
  • Metal organic framework nanoparticles for oral protein administration and preparation method of metal organic framework nanoparticles
  • Metal organic framework nanoparticles for oral protein administration and preparation method of metal organic framework nanoparticles

Examples

Experimental program
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Effect test

Embodiment 1

[0029] Example 1 Preparation and Characterization of Oral Insulin Metal Organic Framework Nanoparticles (T@I@U)

[0030] Preparation of UiO-68-NH by Solvothermal Method 2 : amino-TPDC (10.5mg, 0.031mmol) and ZrOCl 2 ·8H 2 O (8.3 mg, 0.026 mmol) was dissolved in 2 mL DMF. The mixture was sonicated for 5 minutes until it was clear. 40 µL of acetic acid was added to the mixture, which was then heated at 90 °C for 6 h. The mixture was centrifuged at 11000 rpm and washed 3 times with DMF to obtain purified UiO-68-NH 2 . Continue to centrifuge 3 times at 11000rpm to exchange DMF into ddH 2 O.

[0031] Under the condition of stirring at room temperature, 50-300μL of insulin solution (20mg / mL, pH=2.0, dilute hydrochloric acid as solvent) was added dropwise to 4mL of newly synthesized UiO-68-NH 2 (0.25mg / mL) aqueous solution, stirring continuously for 12 hours to obtain insulin@MOF nanoparticles (I@U). Subsequently, 40 μL of transferrin aqueous solution (5 mg / mL) was added t...

Embodiment 2

[0033] Example 2 Detection of Insulin Activity

[0034] In order to verify that insulin still has considerable biological activity during the preparation of nano-preparations and the release of nano-preparations, in this example, I@U and T@I@U freshly prepared according to the method in Example 1 were added at 37 Immerse in 1 mL of PBS buffer for 24 hours at °C, and centrifuge at low temperature (11000 rpm) to obtain the supernatant. The released insulin content in the supernatant was measured using a BCA kit, and then the released insulin (5 IU / kg) and the unloaded insulin (5 IU / kg) were administered to SD rats overnight fasted by subcutaneous injection. The blood glucose concentration of rats at different time points was measured. The result is as image 3 As shown, it shows that the insulin metal organic framework nanoparticles prepared by the present invention will not damage the biological activity of insulin during the preparation process.

Embodiment 3

[0035] Example 3 Research on the protective properties of T@I@U on insulin

[0036] To determine UiO-68-NH 2 Whether insulin can be protected from digestive enzymes, freshly prepared I@U and T@I@U according to the method in Example 1 were incubated in HBSS buffer containing trypsin (1 mg / mL) at 37°C. Aliquots (100 μL) were withdrawn at specific time intervals, 200 μL of DMSO containing 0.1% trifluoroacetic acid was added to stop the enzymatic reaction, and the concentration of insulin in the solution was determined with an Elisa kit. Such as Figure 4 As shown, I@U and T@I@U can well protect insulin from destruction within 2 hours.

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Abstract

The invention discloses metal organic framework nanoparticles for oral protein administration and a preparation method of the metal organic framework nanoparticles, and belongs to the technical field of pharmaceutics. The metal organic framework nanoparticles provided by the invention can promote oral absorption of protein / polypeptide with the molecular weight of at most 10000 Daltons. The metal organic framework nano-particle is prepared by loading a nano-scale acid-resistant metal organic framework with a small molecule protein / polypeptide drug through hydrophobic interaction and modifying a targeting molecule on the surface of the nano-scale acid-resistant metal organic framework. The porous acid-resistant metal organic framework shows high drug loading capacity and strong protectiveness to protein, and shows good biocompatibility and sustained and controlled release kinetics in vivo. The targeting molecule can target a receptor on an intestinal epithelial cell membrane, the problem that the permeation efficiency of protein in an intestinal epithelial cell layer is extremely low is solved, and the oral bioavailability of the protein is improved. The preparation method is simple and convenient, the production cost is low, and painless, controlled-release and convenient protein oral administration is expected to be realized.

Description

technical field [0001] The invention belongs to the technical field of pharmacy, and in particular relates to a metal-organic framework nanoparticle for oral protein administration and a preparation method thereof. Background technique [0002] Peptide and protein drugs refer to peptide and protein biological drugs used for prevention, treatment and diagnosis, which have the advantages of high activity, strong specificity, low toxicity, and clear biological functions. Due to the complex preparation process of peptide and protein drugs, low delivery efficiency, poor bioavailability and many other reasons, their route of administration is more critical. However, protein drugs have poor membrane permeability and short half-life, and are easily destroyed in strong acid, strong alkali and protease-rich environments. Therefore, subcutaneous injection is the main mode of administration of protein. Long-term frequent protein injections will bring considerable pressure and pain to ...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/52A61K47/62A61K9/00A61K38/28
CPCA61K47/6949A61K47/52A61K47/62A61K9/0053A61K38/28
Inventor 田间邹俊捷
Owner WUHAN UNIV
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