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Preparation method of submicron order core/shell structure PLGA (Poly(Lactic-co-Glycolic) microsphere with uniform particle size

A submicron-scale, shell-structured technology, which is applied in the field of tissue engineering and drug controlled release materials, can solve the problems of uneven size and complex methods, and achieve the effects of uniform particle size, simple preparation process, and simple device

Active Publication Date: 2014-09-17
天津渤化讯创科技有限公司
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0005] The existing methods for preparing core / shell structure poly(lactide-co-glycolide) (PLGA) microspheres are complicated and require special equipment. / Solvent volatilization and diffusion method to prepare submicron-sized core / shell structure poly(lactide-co-glycolide) (PLGA) microspheres with uniform particle size has not been reported in the literature

Method used

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  • Preparation method of submicron order core/shell structure PLGA (Poly(Lactic-co-Glycolic) microsphere with uniform particle size
  • Preparation method of submicron order core/shell structure PLGA (Poly(Lactic-co-Glycolic) microsphere with uniform particle size

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Embodiment 1

[0018] 1. Dissolve 10mg of bovine serum albumin in 1mL of phosphate buffer to obtain solution 1; dissolve 30mg of PLGA and 24mg of F127 in 3mL of dichloromethane to obtain solution 2; mix 1mL of solution 1 with 3mL of solution 2. Ultrasonic dispersion in an ice bath with a power of 20W for 3 minutes to form colostrum;

[0019] 2. Add 4mL of colostrum to 10mL of calcium chloride solution with a concentration of 2mg / mL, and sonicate in an ice bath with a power of 50W for 10 minutes to form double emulsion;

[0020] 3. After volatilizing the dichloromethane in the double emulsion at room temperature for 4 hours, dialyze in water for 4 hours, and freeze-dry to obtain a submicron-sized core / shell structure poly(lactide-co-ethylene glycol) with uniform particle size. lactide) (PLGA) microspheres, the particle size is about 500nm, and the encapsulation rate of bovine serum albumin is more than 30% (mass).

Embodiment 2

[0022] 1. Dissolve 30 mg of bovine serum albumin and 60 mg of carboxymethyl chitosan in 3 mL of phosphate buffer to obtain solution 1; dissolve 270 mg of PLGA and 90 mg of F127 in 9 mL of dichloromethane to obtain solution 2; Disperse 3mL of solution 1 and 9mL of solution 2 in an ice bath with a power of 30W and ultrasonically disperse for 3 minutes to form colostrum;

[0023] 2. Add 12mL of colostrum to 30mL of calcium chloride solution with a concentration of 1mg / mL, and sonicate in an ice bath with a power of 60W for 10 minutes to form double emulsion;

[0024] 3. After volatilizing the dichloromethane in the double emulsion at room temperature for 4 hours, dialyze in water for 4 hours, and freeze-dry to obtain a submicron-sized core / shell structure poly(lactide-co-ethylene glycol) with uniform particle size. Lactide) (PLGA) microspheres, the particle size is about 600nm, and the encapsulation rate of bovine serum albumin is more than 45% (mass).

Embodiment 3

[0026] 1. Dissolve 10 mg of bovine serum albumin and 50 mg of carboxymethyl chitosan in 1 mL of phosphate buffer to obtain solution 1; dissolve 90 mg of PLGA and 90 mg of F127 in 3 mL of dichloromethane to obtain solution 2; Disperse 1mL of solution 1 and 3mL of solution 2 ultrasonically in an ice bath for 3 minutes at a power of 20W to form colostrum;

[0027] 2. Add 4mL of colostrum to 12mL of calcium chloride solution with a concentration of 2mg / mL, and sonicate in an ice bath with a power of 50W for 10 minutes to form double emulsion;

[0028] 3. After volatilizing the dichloromethane in the double emulsion at room temperature for 4 hours, dialyze in water for 4 hours, and freeze-dry to obtain a submicron-sized core / shell structure poly(lactide-co-ethylene glycol) with uniform particle size. Lactide) (PLGA) microspheres, the particle size is about 600nm, and the encapsulation rate of bovine serum albumin is more than 40% (mass).

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Abstract

The invention discloses a preparation method of submicron core / shell structure poly(lactide-co-glycolide) microspheres with uniform particle size. The microsphere has a core / shell structure, the particle size is 400-600nm, and the average thickness of the shell is 70nm. Its preparation process: Dissolve bovine serum albumin, carboxymethyl chitosan or low molecular weight heparin in phosphate buffer as solution 1, dissolve PLGA and emulsifier F127 in dichloromethane as solution 2, and dissolve solution 1 and Solution 2 is ultrasonically dispersed in an ice bath to form colostrum; then the colostrum is added dropwise to calcium chloride solution, and ultrasonically dispersed in an ice bath to form double emulsion; PLGA microspheres are obtained by volatile solvent, dialysis, centrifugal washing, and freeze-drying . The advantage of the present invention is that the preparation process is simple. At the same time, the core / shell structure of the microspheres can pack drugs into the core, with uniform particle size, predictable drug release behavior, and easy compounding with tissue engineering scaffolds.

Description

technical field [0001] The invention relates to a preparation method of poly(lactide-co-glycolide) (PLGA) microspheres with submicron core / shell structure and uniform particle size, which belongs to tissue engineering and drug controlled release material technology. Background technique [0002] poly(lactide- co -glycolide) (PLGA) has good biodegradability and biocompatibility, and the PLGA spheres prepared by it have been widely studied as drug release carriers (Xu Q X, Chin S E, Wang Ch H, Pack D W . Biomaterials, 2013, 34: 3902-3911). [0003] Core / shell structure PLGA microspheres, as biomacromolecule and drug slow-release carriers, can coat a large amount of drugs, and its core layer can effectively realize the controlled release of drugs. There are template methods and non-template methods for preparing core / shell microspheres. Among them, the preparation of core / shell structure PLGA microspheres mostly adopts non-template, mainly including spray drying method, dro...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K47/34
Inventor 袁晓燕韩凤选
Owner 天津渤化讯创科技有限公司
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