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Superparamagnetic nano-iron modified exosome drug-loading nano-system, preparation method and blood glucose response method thereof

A nano-loaded drug and exosome technology, which is applied in the direction of pharmaceutical formulas, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of short half-life of therapeutic effect and application restrictions, and achieve the goal of polypeptide drugs. High drug loading, low immunogenicity, and improved therapeutic effect

Pending Publication Date: 2020-04-21
饶磊
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the therapeutic effect of BAY is limited in clinical application due to its short half-life in vivo.

Method used

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  • Superparamagnetic nano-iron modified exosome drug-loading nano-system, preparation method and blood glucose response method thereof
  • Superparamagnetic nano-iron modified exosome drug-loading nano-system, preparation method and blood glucose response method thereof
  • Superparamagnetic nano-iron modified exosome drug-loading nano-system, preparation method and blood glucose response method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 Exosome Nano-Drug Loading System Modified by Superparamagnetic Nano-iron

[0040] (1) Preparation and drug loading of carriers

[0041] Exosomes are used to load polypeptide drugs, and the electroporation method is used to complete the entrapment of exosomes on polypeptide drugs, and obtain peptide-loaded exosomes; the specific method is as follows:

[0042] a) Collect the serum with a centrifugal force of 20,000g, centrifuge at a low temperature of 4°C for 30min, take the supernatant and continue to centrifuge at a centrifugal force of 110,000g at 6°C for more than 1h, collect the precipitate, and resuspend it with PBS buffer (mix the precipitate with PBS buffer Mix well, let the precipitate disperse and suspend in PBS buffer), and obtain serum exosomes.

[0043] b) 50 μL of 1 mg / mL peptide drug BAY solution and 1 mg / mL exosome suspension were mixed and stirred at a volume ratio of 1:3, and the electroporation drug loading was completed by one pulse at a vol...

Embodiment 4B

[0084] Example 4 Evaluation of long-term therapeutic effect of BAY-exosome-SPION under the action of external magnetic field

[0085] Experimental method: Diabetic mice (BKS.Cg-m+ / +Leprdb / J) were randomly divided into 4 groups, 6 in each group, and normal mice (C57BLKS / J Db / +) were used as the control group.

[0086] Control group: daily intravenous injection of 0.4mL distilled water for 8 weeks;

[0087] Model group: intravenous injection of 0.4mL normal saline every day for a total of 8 weeks;

[0088] BAY group: intravenous injection of BAY (5mg / kg) every day for 8 weeks in total;

[0089] BAY-exosome-SPION group: daily intravenous injection of BAY-exosome-SPION (5 mg / kg according to BAY), for 8 weeks in total;

[0090] BAY-exosome-SPION / MF group: daily intravenous injection of BAY-exosome-SPION (5 mg / kg according to BAY), and applying a magnetic field near the pancreas for 1 hour, twice a day, for a total of 8 weeks.

[0091] After 8 weeks of treatment, glycosylated hem...

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Abstract

The invention provides an exosome nano drug loading system modified by superparamagnetic nano-iron. The exosome nano drug loading system comprises an exosome for loading an insulin secretion-promotingdrug and superparamagnetic nano-iron, wherein the superparamagnetic nano-iron is distributed on the surface of the exosome and is connected to the exosome through the combination of transferrin and atransferrin receptor on the surface of the exosome, and the superparamagnetic nano-iron enables the exosome carrier to have targeting ability and blood glucose responsiveness under the action of an external magnetic field. According to the invention, the exosome loads a diabetes medicine, an exosome nano-carrier is prepared, superparamagnetic nano-iron SPION is adopted as an exosome target head to achieve targeted delivery, pancreatic tissue is targeted through an external magnetic field, the drug carrier is endowed with blood glucose responsiveness, and a nano drug delivery system capable ofeffectively prolonging the in-vivo half-life period of diabetes drugs and having blood glucose response is obtained.

Description

technical field [0001] The invention belongs to the field of nano-drug loading system, and in particular relates to a construction method and application of targeted exosomes for crude secretion drug loading of diabetes. Background technique [0002] Diabetes is one of the most common chronic diseases. Decreased β-cell function and chronic insulin resistance in type 2 diabetes are accompanied by hyperglycemia and hyperlipidemia, which in turn may lead to many complications, such as ketoacidosis, hypertension, atherosclerosis, eye disease and diabetic nephropathy. To prevent and treat hyperglycemia, pancreatic β-cells must sense and appropriately respond to postprandial increases in blood glucose, and therefore, therapies that trigger β-cell insulin production in response to hyperglycemia are among the most important strategies in the treatment of type 2 diabetes. Glinides and sulfonylureas are commonly used in the treatment of type 2 diabetes, but they have poor glycemic re...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/52A61K47/46A61K47/36A61K38/16A61P3/10
CPCA61K47/6929A61K47/52A61K47/46A61K47/36A61K38/16A61P3/10Y02A50/30
Inventor 庄满娇其他发明人请求不公开姓名
Owner 饶磊
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