Polypeptide or protein nanoparticles based on hydrogen-bonded complexation, and preparation method and application thereof

A protein and complexation technology, applied in the field of biomedicine, can solve the problems of low drug loading efficiency, inability to effectively wrap, affect the biological activity of peptide and protein drugs, etc.

Inactive Publication Date: 2019-01-18
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, when the peptides and proteins are weakly charged, they cannot be effectively encapsulated; on the other hand, peptides and protein molecules may contain hydrophobic regions, and they can also be encapsulated by the hydrophobicity of the carrier. However, in the process of nano-preparation Requires the participation of organic solvents, so it will affect the biological activity of peptide and protein drugs, and the drug loading efficiency is usually low

Method used

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  • Polypeptide or protein nanoparticles based on hydrogen-bonded complexation, and preparation method and application thereof
  • Polypeptide or protein nanoparticles based on hydrogen-bonded complexation, and preparation method and application thereof
  • Polypeptide or protein nanoparticles based on hydrogen-bonded complexation, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1 Preparation of exenatide-loaded nanoparticles and enteric-coated microcapsule preparations using FNC technology

[0083] 1. Preparation of tannic acid (TA) and exenatide (EXE) nanocomposite cores

[0084] TA was dissolved in deionized water at a concentration of 0.1-0.9 mg / mL. EXE was dissolved in 0.2% acetic acid solution (HAc), and then the pH value was adjusted to different pH values ​​(5.5-6.8) with NaOH solution, and the concentration of EXE solution was 0.3 mg / mL. The TA solution is distributed in the first and second channels, and the EXE solution is distributed in the third and fourth channels, such as figure 1 As shown, the flow rate of the four channels is the same, adjust the flow rate of the channel, 5mL / min, 10mL / min, 20mL / min, 30mL / min, 40mL / min, 50mL / min, so that the two solutions pass through the four channels to the vortex mixing area Mix to obtain the nanocomposite core (NC) of TA and EXE.

[0085] figure 2 Shown is the effect of flow ra...

Embodiment 2

[0097] Embodiment 2 in vitro drug release experiment

[0098] Three preparations of NC, NP and E-NP were prepared under optimal conditions using RITC-labeled EXE for use. The E-NP preparation was placed in HCl solution with pH=2.5, incubated at 37°C in a shaker at 150 rpm, centrifuged at 10,000 rpm for 10 min every 2 h, and the supernatant was taken to measure the concentration of EXE. Figure 10 When pH = 2.5, the EXE release curves of E-NP prepared with different concentrations of Eudragit can be seen from the figure, when the concentration of Eudragit is 0.9mg / mL, 1.2mg / mL, and 1.5mg / mL, within 2h, respectively There are 50%, 18% and 7% of EXE released, which shows that when the concentration of Eudragit is low, a large amount of EXE is released, which cannot effectively protect EXE from passing through the strong acid environment of the stomach. When the concentration of Eudragit increases to 1.5 mg / mL, it can effectively protect EXE from rapid release in the acidic envir...

Embodiment 3

[0100] Example 3 Small Intestine Permeability Test of Exenatide Nanoparticles Loaded

[0101] Two preparations of NC and NP were prepared under optimal conditions using RITC-labeled EXE for use. The SD rats were fasted for 12 hours, and after anesthesia, the duodenum, jejunum, and ileum of the small intestine of the rats were surgically removed with a length of 5 cm each, and then the rats were sacrificed. Both ends of the small intestine in different parts were ligated, and 1 mL of EXE solution, NC particle suspension, and NP particle suspension were injected, and then the small intestine was placed in 10 mL of krebs ringer buffer, and dialyzed in a shaker at 150 rpm at 37°C. Every 0.5h, take out 1mL of dialysate, measure the concentration of EXE in it, and use the formula (3-3) to calculate the apparent permeability coefficient (PAPPvalue) of different EXE preparations.

[0102]

[0103] in, is the flux of fluorescently labeled nanoparticles or EXE permeating from the ...

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Abstract

The invention discloses a polypeptide or protein nanoparticle based on hydrogen-bonded complexation and a preparation method and application thereof. The nanoparticles comprise a polyphenol compound carrier such as tannic acid as a hydrogen bond donor, a polypeptide or a protein drug such as a glucagon-like peptide as a hydrogen bond acceptor 1 analog (exenatide), salmon calcitonin or insulin, etc., and chitosan, polyvinylpyrrolidone or hyaluronic acid, etc. coated on that surface of the particle as stabilizer and/or functional molecule. The nanoparticles of the invention have extremely high encapsulation efficiency and drug loading capacity, and the prepared therapeutic polypeptide or protein drug nanoparticles are suitable for oral delivery or subcutaneous injection application, and havegreat application prospect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and more specifically relates to a hydrogen-bond complex-based polypeptide or protein drug nano-preparation and its preparation method and application. Background technique [0002] Peptide or protein drugs have the advantages of strong specificity and high efficacy, so they are widely used in regulating physiological processes and treating diseases. Due to their hydrophilicity and high molecular weight, polypeptide or protein molecules are difficult to cross various biological barriers in the body, such as mucus barriers, gastrointestinal barriers, etc., so as to reach the target site and perform their physiological functions; polypeptide or protein drugs are easily The enzymes in the body are degraded, and the blood circulation time in the body is also short, so repeated administration is required for treatment, which results in poor compliance of patients. Through the nano-formulation of ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/54A61K47/61A61K38/22A61K38/28A61P3/10
CPCA61K38/22A61K38/28A61K47/6929A61K47/6939A61P3/10
Inventor 刘志佳田厚宽陈永明刘利新孙立泷乐志成
Owner SUN YAT SEN UNIV
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