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Preparation method of drug-loaded microspheres with tumor microenvironment responsiveness

A tumor microenvironment, drug-loaded microsphere technology, applied in the field of drug-loaded microsphere preparation with tumor microenvironment responsiveness, can solve the problems of single functionality and fast drug release, and achieve great value and good biocompatibility. Sexual and Biofunctional Effects

Inactive Publication Date: 2020-07-14
NANJING DRUM TOWER HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The purpose of the present invention is to solve the shortcomings of the traditional drug-loaded microspheres, such as excessive drug release rate and single function, and provide a preparation method of drug-loaded microspheres with tumor microenvironment responsiveness, using silica colloidal crystal microspheres as templates , preparing inverse opal photonic crystal microspheres by perfusing hydrogel materials, and wrapping MnO on the microspheres 2 Prepared as a multifunctional microsphere with tumor responsiveness, the drug-loaded microsphere with tumor microenvironmental responsiveness designed in the present invention is an ideal carrier for tumor site-specific drug delivery

Method used

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  • Preparation method of drug-loaded microspheres with tumor microenvironment responsiveness
  • Preparation method of drug-loaded microspheres with tumor microenvironment responsiveness
  • Preparation method of drug-loaded microspheres with tumor microenvironment responsiveness

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preparation example Construction

[0027] see figure 1 , a method for preparing drug-loaded microspheres with tumor microenvironment responsiveness, wherein, a is silica colloidal crystal microsphere template microspheres, b is silica colloidal crystal microspheres filled with hydrogel microspheres, and c is Inverse opal microspheres, comprising the following steps:

[0028] S1: Using the silica nanoparticle dispersion as the internal phase and methyl silicone oil as the external phase, inject the external phase and the internal phase into the corresponding channels of the microfluidic device, and collect through the output channel of the microfluidic device. In the container, dry and stand still to obtain silica colloidal crystal microspheres, then soak silica colloidal crystal microspheres in n-hexane to remove silicone oil, wash them and place them in a muffle furnace for high-temperature calcination to obtain Mechanically strong silica colloidal crystal microsphere template;

[0029] S2: immerse the silic...

Embodiment 1

[0034] Preparation of chitosan-based tumor-responsive drug-loaded microspheres

[0035] (1) Preparation of silica colloidal crystal beads (SCCB) template:

[0036] Using a microfluidic device, the silica nanoparticle dispersion with a concentration of 18% was used as the internal phase, and methyl silicone oil was used as the external phase. The flow rate of the internal phase was set to 1mL / h, and the flow rate of the external phase was set to 6mL / h. The colloidal crystal microspheres were collected in a container, and placed in an oven at a temperature of 75°C for 12 hours. Then, the silica colloidal crystal microspheres were soaked in n-hexane, and the silicone oil was eluted with n-hexane, and finally washed The silicon dioxide colloidal crystal microspheres were calcined in a muffle furnace at a high temperature of 800° C. to obtain a silica colloidal crystal microsphere template with certain mechanical strength.

[0037] (2) Preparation of chitosan hydrogel inverse opal...

Embodiment 2

[0046] Preparation of a tumor-responsive drug-loaded microsphere based on silk fibroin

[0047] (1) Preparation of silica colloidal crystal beads (SCCB) template:

[0048] Using a microfluidic device, the silicon dioxide nanoparticle dispersion with a concentration of 20% is used as the internal phase, and methyl silicone oil is used as the external phase. The flow rate of the internal phase is set to 1mL / h, and the flow rate of the external phase is 6mL / h. The colloidal crystal microspheres were collected in a container, and placed in an oven at a temperature of 75°C for 12 hours. Then, the silica colloidal crystal microspheres were soaked in n-hexane, and the silicone oil was eluted with n-hexane, and finally washed The silicon dioxide colloidal crystal microspheres were calcined in a muffle furnace at a high temperature of 800° C. to obtain a silica colloidal crystal microsphere template with certain mechanical strength.

[0049] (2) Preparation of silk fibroin hydrogel in...

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Abstract

The invention discloses a preparation method of drug-loaded microspheres with tumor microenvironment responsiveness. The microspheres are mainly prepared based on a silica colloidal crystal microsphere template and a hydrogel, and loading and encapsulation of a drug are realized respectively through the physical adsorption of the drug and the wrapping of a tumor microenvironment responsive material. The drug-loaded microspheres are prepared by the microfluidic technology, have a three-dimensional penetration nano-porous structure, and can realize loading with a large amount and slow-release ofthe drug. In addition, the tumor-responsive material wrapped on the surface of the microspheres can protect the drug from being degraded until the drug reaches the tumor site. The drug-loaded microspheres prepared by the method of the invention have good biocompatibility and biological functionality, and exhibit great value in the field of tumor drug delivery.

Description

technical field [0001] The invention relates to the field of biomedical materials, in particular to a method for preparing drug-loaded microspheres with tumor microenvironment responsiveness. Background technique [0002] Metformin is a common drug for the treatment of type 2 diabetes, and metformin has been reported to have anti-tumor activity in recent years. The main mechanism is that metformin can reduce the stability of PD-L1 and inhibit the PD1 / PD-L1 signaling pathway, thereby enhancing the immune killing ability of cytotoxic T cells. However, metformin is a small molecule drug, which is easily degraded and inactivated in the body, and the effective drug concentration is maintained for a short time. [0003] Drug-loaded microspheres in the biomedical field can well solve the above problems. The three-dimensional interconnected nano-network structure endows the inverse opal microsphere with a huge surface area, which can realize a large amount of drug loading and slow...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K47/02A61K47/36A61K47/42A61K31/155A61P35/00
CPCA61K9/501A61K9/5036A61K9/5052A61K31/155A61P35/00
Inventor 赵远锦文元元王月桐
Owner NANJING DRUM TOWER HOSPITAL
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