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Preparation method of poly(lactic-co-glycolic acid based magnetic medicine-carrying hollow microspheres

A technology of polylactic acid glycolic acid and hollow microspheres, which is applied in the field of preparation of drug-loaded nanomaterials, can solve the problems of not finding PLGA hollow microspheres, and achieve the effects of reducing mutual collisions, promoting curing, and reducing aggregation

Inactive Publication Date: 2013-09-11
DONGHUA UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The literature and patent results of domestic and foreign searches for therapeutic diagnostic agents related to PLGA microspheres show that: at present, no 3 o 4 Report on the preparation and application of nanoparticles and anticancer drug doxorubicin hydrochloride PLGA hollow microspheres

Method used

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  • Preparation method of poly(lactic-co-glycolic acid based magnetic medicine-carrying hollow microspheres
  • Preparation method of poly(lactic-co-glycolic acid based magnetic medicine-carrying hollow microspheres
  • Preparation method of poly(lactic-co-glycolic acid based magnetic medicine-carrying hollow microspheres

Examples

Experimental program
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Effect test

Embodiment 1

[0062] (1) with 2mL CH 2 Cl 2 Dissolve 100mg PLGA, 0.4mg magnetic Fe 3 o 4 Nanoparticles; Dissolve 4mg DOX in 200μL ultrapure water, mix the organic phase and the aqueous phase, and ultrasonically treat with a cell disruptor for 30s in an ice-water bath to form a W / O emulsion;

[0063] (2) Transfer the W / O emulsion in step 1 into 10mL of 5% PVA aqueous solution, and use a homogenizer to shear (9500rpm, 5min) in an ice-water bath to make the droplets form a W / O / W emulsion with a relatively uniform size;

[0064] (3) Pour the W / O / W emulsion from step 2 into 80 mL of 2% isopropanol aqueous solution and magnetically stir for 1 h, then centrifuge (3500 rpm, 3 min), discard the supernatant, and wash the centrifuged residue with 90 mL of ultrapure water. Repeat the above centrifugation and water washing operation for more than three times until the centrifugation liquid is clear and colorless. After centrifugation, redisperse the centrifugation residue in 30mL ultrapure water, fre...

Embodiment 2

[0067] Check the two kinds of material PLGA-Fe synthesized by embodiment 1 and comparative example 1 with the gray value of in vitro US test 3 o 4 -DOX microspheres with PLGA-Fe 3 o 4 US imaging effect of microspheres. Take 10 mg of the sample of Example 1 and dissolve it in 2 mL of PBS buffer to prepare a solution with a concentration of microspheres of 5 mg / mL, and put it into a 2 mL centrifuge tube. Take 10 mg of the sample of Comparative Example 1 and dissolve it in 2 mL of PBS buffer to prepare a solution with a microsphere concentration of 5 mg / mL, and put it into a 2 mL centrifuge tube. The ultrasonic imaging images of each sample were tested with a medical contrast-enhanced ultrasound apparatus, and the gray value of the ultrasonic imaging images was obtained by processing the ultrasonic imaging images with ImageJ software. attached Figure 5 (a) is the US picture of the sample (where 1 is PLGA-Fe 3 o 4 -DOX microspheres and 2 for PLGA-Fe 3 o 4 microspheres), ...

Embodiment 3

[0069] T measured by in vitro MR 2 value to check the material PLGA-Fe synthesized in Example 1 3 o 4 - MRI imaging effect of DOX microspheres. Take 46.3 mg of the sample of Example 1 and dissolve it in 2 mL of PBS buffer to prepare a solution with an iron concentration of 0.6 mM, and then dilute to 1 mL of each solution with an iron concentration of 0.0375, 0.075, 0.15, 0.3, and 0.6 mM. Test the T of each sample with a medical 3T MR tester 2 relaxation time and derive 1 / T 2 The linear relationship between the value and iron concentration. attached Figure 6 (a) is the T of the sample 2 - Weighted spin echo black and white image, attached Figure 6 (b) is the T of the material 2 Linear plot of the inverse of relaxation time as a function of iron concentration. Figure 6 (b) T of the samples at various concentrations of the material 2 Relaxation time 1 / T 2 The value of the linear relationship with the iron concentration is good, the longitudinal relaxation rate of th...

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Abstract

The invention relates to a preparation method of poly(lactic-co-glycolic acid based magnetic medicine-carrying hollow microspheres. The preparation method comprises the following steps: adding magnetic Fe3O4 nanoparticles into a poly(lactic-co-glycolic acid solution so as to obtain an oil phase, dissolving a hydrochloric acid doxorubicin DOX into ultrapure water so as to obtain a water phase, mixing the oil phase with the water phase, and carrying out ultrasonic processing so as to obtain a W / O (water-in-oil) emulsion; adding the W / O emulsion into a polyvinyl alcohol PVA solution, and homogenizing so as to obtain a W / O / W (water-oil-water) emulsion; adding the W / O / W emulsion into an isopropyl alcohol aqueous solution, stirring for 1-4h, carrying out centrifugal washing, dispersing the obtained mixture in water, and finally carrying out freeze drying. According to the preparation method, the preparation process is simple, and experiment conditions are normal pressure and temperature; and the product prepared according to the preparation method has a good US / MRI imaging effect and a good medicine sustained release effect, and provides a reference for the development of novel multi-functional therapeutic and diagnostic medicaments.

Description

technical field [0001] The invention belongs to the field of preparation of drug-loaded nanometer materials, in particular to a method for preparing magnetic drug-loaded hollow microspheres based on poly(lactic-co-glycolic acid) copolymers. Background technique [0002] Therapeutic diagnosis technology refers to the technology that combines medical diagnosis and treatment, such as ultrasound (US), magnetic resonance (MR), X-ray tomography (CT) imaging technology, etc.; treatment methods include chemotherapy, radiotherapy, hyperthermia, etc. This combination has important implications for cancer specificity and adaptability, and it has given rise to the search for novel theranostics. Although only a few therapeutic diagnostic agents have been successfully developed at present, such as Ke et al. (H.Ke, et a1. Angew. Chem. 2011, 123, 3073–3077.) prepared microcapsules with PLA, and prepared gold nanoshells outside the microcapsules, Get very good US imaging contrast and hypert...

Claims

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Application Information

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IPC IPC(8): A61K49/22A61K49/18A61K49/12A61K31/704A61K47/34A61K9/19A61P35/00
Inventor 史向阳刘伟娜温诗辉张贵祥姜露莹
Owner DONGHUA UNIV
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