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Composite hydrogel loaded with exosome and preparation method thereof

A composite hydrogel and exosome technology, applied in the field of biomedical engineering, can solve the problems that exosomes lack tissue specificity, cannot meet local drug delivery, and do not have injectability, etc., and achieve tumor permeability residence time , gel time and adjustable, highly reproducible results

Inactive Publication Date: 2019-06-25
STOMATOLOGY AFFILIATED STOMATOLOGY HOSPITAL OF GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

200610076650.X discloses a preparation method of hyaluronic acid hydrogel for brain injury repair, under the mediation of carbodiimide hydrochloride, crosslinking with oxalic acid dihydrazide, but the hydrogel Glue is not injectable
CN108084461A discloses a preparation method of self-crosslinking mercaptolated hyaluronic acid-collagen composite hydrogel, which is formed by crosslinking reactions between sulfhydryl groups, and also lacks injectability and cannot meet the requirements of local administration. need
CN104140541A discloses an injectable hyaluronic acid hydrogel, which is synthesized by a three-step chemical method, and the preparation process is relatively complicated
However, exosomes lack tissue specificity in vivo

Method used

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  • Composite hydrogel loaded with exosome and preparation method thereof
  • Composite hydrogel loaded with exosome and preparation method thereof
  • Composite hydrogel loaded with exosome and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] First configure a 6% (w / v) oxidized hyaluronic acid solution; then configure a mixed solution of loaded curcumin exosomes and oxalic acid dihydrazide (the concentration of exosomes is 0.4 mg / mL (w / v)); Then the oxidized hyaluronic acid solution was mixed with the mixed solution of loaded curcumin exosomes-oxalic acid dihydrazide at a volume ratio of 4:1, and allowed to stand at room temperature for reaction to obtain a composite hydrogel loaded with curcumin exosomes, Record the gel time; figure 1 Extracted and purified exosomes are shown; figure 2 Shown is the composite hydrogel loaded with curcumin exosomes; as image 3 As shown, the composite hydrogel has a porous sheet microstructure; the composite hydrogel has injectable properties, see Figure 4 .

Embodiment 2

[0054] First configure a 6% (w / v) oxidized hyaluronic acid solution; then configure a mixed solution of loaded indocyanine green exosomes and oxalic acid dihydrazide (the concentration of exosomes is 0.4 mg / mL (w / v) ); then mix the oxidized hyaluronic acid solution with the loaded indocyanine green exosomes-oxalic acid dihydrazide mixed solution at a volume ratio of 4:1, and leave to react at room temperature to obtain the loaded indocyanine green exosomes The composite hydrogel, record the gel time; Figure 5 Shown is the composite hydrogel loaded with indocyanine green exosomes; as Figure 6 As shown, the composite hydrogel has a lamellar structure; the composite hydrogel has injectable properties, see Figure 7 .

Embodiment 3

[0056] First configure 6% (w / v) oxidized hyaluronic acid solution; then configure the mixed solution of loaded curcumin / indocyanine green exosomes and oxalic acid dihydrazide (the concentration of exosomes is 0.4 mg / mL (w / v)); then mix the oxidized hyaluronic acid solution with the loaded curcumin exosome-oxalic acid dihydrazide mixed solution at a volume ratio of 4:1, and leave it to react at room temperature to obtain the loaded curcumin / indocyanine Composite hydrogel of green exosomes, recording gel time; Figure 8 Shown is the composite hydrogel loaded with curcumin / indocyanine green exosomes; as Figure 9 As shown, the composite hydrogel has a porous sheet microstructure; the composite hydrogel has injectable properties, see Figure 10 .

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Abstract

The invention discloses a composite hydrogel loaded with an exosome and a preparation method thereof, which belong to the technical field of biomedical engineering. The preparation method comprises the following steps: firstly separating and purifying the exosome from the C57 mouse mesenchymal stem cells, then uniformly dispersing the exosome in an oxidized hyaluronic acid solution, and performinga cross-linked reaction by an aldehyde group of the oxidized hyaluronic acid and a hydrazide group of oxalyl dihydrazide to obtain the composite hydrogel. The preparation method is simple, rapid, andhighly reproducible. The prepared exosomes-loaded composite hydrogel has the advantages of high local concentration and low systemic toxicity, and has tumor permeability and long residence time. In addition, the composite hydrogel has injectability, biodegradability and drug release properties, and the gel time is fast and can be regulated.

Description

technical field [0001] The invention belongs to the technical field of biomedical engineering, and in particular relates to a composite hydrogel loaded with exosomes and a preparation method thereof. Background technique [0002] Whether it is a resectable or unresectable tumor, local sustained release plays an important role in preoperative control and postoperative adjuvant chemotherapy. Its main advantages are: direct contact between the drug and the tumor, greatly increasing the effective concentration of the drug in the tumor cells; Minimize systemic toxicity and side effects; the drug is released continuously without frequent administration. In 1996, the US Food and Drug Administration approved the use of an implantable drug-loaded wafer (Wafer) to treat relapsed Gliomas. The Wafer is composed of a degradable polymer loaded with 3.8% carmustine. The researchers implanted the drug-loaded Wafer along the edge of the gap after Gliomas resection, increasing the concentrat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K9/06A61K47/36A61K47/46A61K31/12A61P35/00
Inventor 谢茂彬王金恒陈晓明周苗
Owner STOMATOLOGY AFFILIATED STOMATOLOGY HOSPITAL OF GUANGZHOU MEDICAL UNIV
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