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Nanocomposite temperature-sensitive gel and preparation method and application thereof

A temperature-sensitive gel and nano-composite technology, which can be used in pharmaceutical formulations, drug combinations, preparations for in vivo tests, etc., can solve the problem of limiting the clinical therapeutic effect of chemotherapy drugs, the rapid emergence of tumor cell drug resistance, and dose-dependent side effects, etc. Problems, suitable for large-scale production, simple preparation method, strong tumor targeting effect

Inactive Publication Date: 2012-07-04
SHANGHAI INST OF ONCOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

A major problem is the general lack of selectivity of chemotherapy drugs, leading to serious dose-dependent side effects, which greatly limits the clinical therapeutic effect of chemotherapy drugs
Another concern is the rapid emergence of drug resistance in tumor cells

Method used

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  • Nanocomposite temperature-sensitive gel and preparation method and application thereof
  • Nanocomposite temperature-sensitive gel and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Preparation and application of PLGA-PLL-cRGD thermosensitive composite gel loaded with 5-fluorouracil (5Fu)

[0051] Preparation by double emulsion method: Dissolve 8 mg PLGA-PLL-cRGD in 400 μL dichloromethane, add 40 μL 5-fluorouracil (5-Fu) solution with a concentration of 20 mg / mL, and after ultrasonic emulsification, add 4.4 mL 2wt% porine Loxamer F68 aqueous solution, sonication again. Then stir at room temperature for 3 h to remove the organic phase to obtain nanoparticle suspension. The above-mentioned nanoparticle particle size that makes is controlled at 10-1000nm ( figure 1 A).

[0052] Add F-127 to the above aqueous dispersion of nanoparticles to make the concentration 15%, and obtain a composite gel.

[0053] Rabbit liver cancer model, open the abdomen to expose the tumor, inject 10-50 μl of gel into the tumor, seal it with bioprotein glue, and suture it. After 2 weeks, the tumor showed a shrinking tendency.

Embodiment 2

[0055] Preparation and application of mPEG-PLGA-PLL-cRGD temperature-sensitive composite gel loaded with gemcitabine hydrochloride (GEM)

[0056] Preparation by double emulsion method: Dissolve 8 mg of mPEG-PLGA-PLL-cRGD in 400 μL of dichloromethane, add 20 μL of GEM solution with a concentration of 40 mg / mL, and after ultrasonic emulsification, add 4.4 mL of 2wt% poloxamer F68 aqueous solution , sonicate again. Then stir at room temperature for 3 h to remove the organic phase to obtain nanoparticle suspension. The above-mentioned nanoparticle particle size that makes is controlled at 10-1000nm ( figure 1 B).

[0057] Add F-127 to the above solution to make the concentration 13%, to obtain the gel.

[0058] In the orthotopic tumor model of pancreatic cancer in nude mice, the left abdomen was opened to expose the tumor, and 2-5 μl of the above gel was injected into the tumor, sealed with bioprotein glue, and sutured. After 2 weeks, the tumor showed a shrinking tendency.

Embodiment 3

[0060] Preparation and application of mPEG-PLGA-PLL thermosensitive composite gel loaded with siRNA

[0061] Prepared by double emulsion method, take 20mg material mPEG-PLGA-PLL and dissolve in 1000μL dichloromethane or a mixed solvent of dichloromethane and acetone, add 4nmoL siRNA solution, ultrasonic emulsification (300W or 500W, 10s×4), then add In 6 mL of 0.5% Pluronic F68 aqueous dispersion medium, ultrasonic emulsification again (300W or 500W, 10s×4). Then stir at room temperature for 0.5-5h to remove the organic phase, to obtain a particle diameter of 100-800nm ​​nanoparticle solution ( figure 1 C), lyophilized.

[0062] Add polyacrylamide to the above aqueous dispersion of nanoparticles to make the concentration 5%, and freeze-dry to obtain a composite xerogel.

[0063] Liver orthotopic tumor model in nude mice, open the abdomen to expose the tumor. Disperse the xerogel with an appropriate amount of saline, inject 2-5 μl into the tumor, and suture. After 2 weeks,...

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Abstract

The invention relates to a nanocomposite temperature-sensitive gel and a preparation method and an application thereof. The preparation method comprises the following steps of: coating antitumor active substances with a high molecular polymer serving as a carrier material to obtain nanoparticles; and adding a temperature-sensitive high molecular material to obtain the nanocomposite temperature-sensitive gel. The preparation method disclosed by the invention is simple and convenient, is suitable for large-scale production, and is particularly suitable for preparing medicaments or diagnostic reagents having the characteristics of long cycle, biodegradability, slow release, passive targeting, active targeting, active substance conveying function and tumor resistance. An antitumor medicament prepared with the method disclosed by the invention is suitable for ways such as intravenous injection, intramuscular injection, hypodermic injection, intradermal injection, intratumor injection, tumor-side injection, oral administration or transdermal medicament delivery and the like, is applied to treatment and diagnosis of pancreatic cancer, liver cancer, lung cancer, gastric cancer, colorectal cancer, esophageal cancer, prostatic cancer, uterine cancer and ovarian cancer, and has a good application prospect.

Description

technical field [0001] The invention belongs to the field of targeted delivery drug carrier and its preparation method and application, in particular to a nanocomposite temperature-sensitive gel and its preparation method and application. Background technique [0002] The clinical application of chemotherapy drugs to treat malignant tumors has achieved certain success in many cases, but there are also some serious problems. A major problem is that chemotherapeutic drugs generally lack selectivity, leading to serious dose-dependent side effects, which greatly limits the clinical therapeutic effect of chemotherapeutic drugs. Another problem is the rapid emergence of drug resistance in tumor cells. Therefore, the development of therapeutic methods that can specifically target tumor cells and cause minimal damage to normal cells has very important significance and broad application prospects. [0003] In recent decades, targeted delivery vectors have attracted much attention a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K47/34A61K47/42A61K48/00A61K49/18A61K49/12A61K49/14A61K49/16A61P35/00
Inventor 段友容沈鸣万智勇孙颖覃刘彬
Owner SHANGHAI INST OF ONCOLOGY
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