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Erythrocyte gel delivery system as well as preparation method and application thereof

A technology for red blood cells and gels, which is applied in the directions of pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., to achieve high drug loading, high biosafety and biodegradability, and a preparation method. Simple and fast effects

Active Publication Date: 2020-05-22
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to solve the problems related to traditional hydrogels, the present invention provides a highly biosafe erythrocyte gel delivery system

Method used

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  • Erythrocyte gel delivery system as well as preparation method and application thereof
  • Erythrocyte gel delivery system as well as preparation method and application thereof
  • Erythrocyte gel delivery system as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1: Synthesis and characterization of erythrocyte gels

[0066] (1) Take out 200 μL of blood rapidly from the vein of the organism;

[0067] (2) Immediately inject the fresh blood obtained in step (1) into a sterile mold, and place it at room temperature for 10 minutes;

[0068] (3) Transfer the preliminarily coagulated blood in step (2) to a sterile vacuum drying oven, and dry it gently at 37°C to obtain red blood cell gel, see figure 1 ;

[0069] (4) Use a rheometer to prove the rheological properties of the gel obtained in step (3), which proves that the erythrocyte gel of the present invention has good mechanical properties ( figure 2 );

[0070] (5) Using a scanning electron microscope (Scanning Electron Microscope, SEM) to perform microscopic imaging of the erythrocyte gel ( image 3 ), proving that the erythrocyte gel has a regular internal structure;

[0071] (6) Record the degradation of the erythrocyte gel carrier in vivo and in vitro, Figure 4 ...

Embodiment 2

[0073] Example 2: Immunostimulation and immune cell recruitment of erythrocyte gel

[0074] (1) After C57BL / 6J mice were anesthetized with 2.5% isoflurane, the erythrocyte gel prepared in Example (1) was implanted subcutaneously in the mice;

[0075] (2) The erythrocyte gels implanted in the body at 0, 1, 3, and 7 days were taken out at the same time, embedded in paraffin for HE tissue section and embedded in OCT gel for fluorescence staining analysis. It can be seen that the erythrocyte gel of the present invention has the function of recruiting immune cells ( Figure 10 ), a large number of white blood cells infiltrated from the edge of the red blood cell gel to the inside ( Figure 11 ), the fluorescent signal of white blood cells gradually increased from the edge of the red blood cell gel to the inside ( Figure 12 ), the overall fluorescence intensity increases with time ( Figure 13 );

[0076] (3) Further use flow cytometry to analyze the immune cells and their subp...

Embodiment 3

[0077] Example 3: Analysis of drug sustained release effect of erythrocyte gel

[0078] (1) Put Cy5.5-CpG-OND and FITC-OVA into the corresponding molds of step (2) of Example 1 respectively, mix with fresh isolated blood according to the steps in Example 1, and dry gently to prepare drug-loaded red blood cell gel;

[0079] (2) Aspirate a small amount of liquid precipitated from the drug-loaded erythrocyte gel, detect the unloaded drug content with a microplate reader, and calculate the drug-loading efficiency of the erythrocyte gel. The efficiencies of OVA and CpG loaded on erythrocyte gel can reach 95% and 83% ( Figure 15 );

[0080] (3) The prepared drug-loaded erythrocyte gel was embedded in OCT gel, and after sectioning, the drug-loading situation was observed through a confocal microscope. The results showed that OVA could be effectively loaded into the erythrocyte gel ( Figure 16 );

[0081] (4) Place the drug-loaded erythrocyte gel in 2 mL of 37°C Phosphate Buffer...

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Abstract

The invention discloses an erythrocyte gel delivery system as well as a preparation method and application thereof, and belongs to the technical field of biological materials. The preparation method comprises the following steps: uniformly mixing an active ingredient or a delivery carrier containing the active ingredient and fresh blood, and performing mild drying after preliminary coagulation toprepare the erythrocyte gel delivery system. The preparation method of the erythrocyte gel delivery system provided by the invention is simple and fast, and the erythrocyte gel delivery system has theadvantages of high drug loading, high biological safety and high biodegradability; erythrocyte gel has the effects of immune stimulation and immune cell recruitment, and can form an immune niche at an implantation site; an immunomodulator and a tumor-associated antigen contained in the erythrocyte gel vaccine prepared by the method stimulates recruited immune cells to differentiate into immune cells with tumor antigen specificity after being implanted, and induce production of highly effective anti-tumor immune responses.

Description

technical field [0001] The invention relates to an erythrocyte gel delivery system, a preparation method and application thereof, and belongs to the technical field of biomaterials. Background technique [0002] Conventional treatment of diseases often requires repeated administration of high doses to patients in order to achieve good prognosis. However, the overall efficiency of the conventional drug administration is low, the patient's compliance is poor, and it is easy to cause serious side effects. Drugs injected intravenously can enter the blood circulation without crossing any barriers, and there is a certain risk of systemic toxicity, which cannot be relieved and cleared in time. Oral administration has a slower onset of action, lower bioavailability, and usually lacks targeting. [0003] In recent years, the rapid development of materials engineering has provided new opportunities for the field of biomedicine. Rationally designed biomaterials can be used to constr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/46A61K39/00A61K39/395A61P35/00
CPCA61K9/06A61K9/0024A61K47/46A61K39/0011A61K39/39558A61P35/00A61K2300/00
Inventor 汪超范亲
Owner SUZHOU UNIV
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