Preparation method and application of tumor-targeted nanometer drug delivery system for cooperative chemotherapy and photodynamic therapy

A photodynamic therapy and drug delivery system technology, applied in the field of biomedicine, can solve the problems of limited application of photodynamic therapy, limited phototoxicity, poor water solubility, etc., and achieve orderly release, high drug loading rate, good slowness The effect of controlled release capability

Inactive Publication Date: 2016-07-13
SHENYANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the single application of photodynamic therapy is limited, mainly due to the disadvantages of phototoxicity, poor water solubility, fast metabolism, and poor targeting.

Method used

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  • Preparation method and application of tumor-targeted nanometer drug delivery system for cooperative chemotherapy and photodynamic therapy
  • Preparation method and application of tumor-targeted nanometer drug delivery system for cooperative chemotherapy and photodynamic therapy
  • Preparation method and application of tumor-targeted nanometer drug delivery system for cooperative chemotherapy and photodynamic therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Preparation of blank FA-CMCS-Ce6 conjugates

[0026] a. Dissolve Ce6 in 0.1% (v / v) dimethylsulfoxide (DMSO) aqueous solution, add 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), reacted at room temperature in the dark for 0.5 hours, then added the activated Ce6-NHS to the CMCS aqueous solution, adjusted the pH to 4.5~5.0, stirred overnight at room temperature in the dark, and obtained Product CMCS-Ce6. The molar ratio of Ce6 / EDC / NHS added therein is 0.5:1:1.1, and the molar ratio of Ce6 / CMCS is 20:1. The product CMCS-Ce6 was placed in a centrifuge, centrifuged at 14,000 rpm for 5 minutes to remove aggregates, and then filtered through an ultrafiltration membrane (molecular weight cut-off 10kDa) to remove free Ce6 active esters to obtain purified CMCS-Ce6.

[0027] b. Dissolve FA in 0.1% (v / v) dimethyl sulfoxide (DMSO) aqueous solution, add dicyclohexylcarbodiimide (DCC) and NHS, react in the dark for 1 hour ...

Embodiment 2

[0028] Example 2: Preparation of a tumor-targeted nano drug delivery system loaded with doxorubicin

[0029] The ion cross-linking method was used to prepare the drug-loaded nanoparticles with CaCl2 as the cross-linking agent. Dissolve the lyophilized FA-CMCS-Ce6 in water, adjust the pH to 7.2, slowly add a certain amount of DOX·HCl aqueous solution into the FA-CMCS-Ce6 solution under stirring, dissolve with 40W ultrasonic, and then add the CaCl2 solution with Drop into the above FA-CMCS-Ce6 solution at a speed of 3 s / drop, and continue to stir for 30 minutes to obtain a DOX / FA-CMCS-Ce6 nanoparticle suspension. Centrifuge the suspension at 16,000 rpm for 30 minutes, collect The precipitate was freeze-dried to obtain DOX / FA-CMCS-Ce6 nanoparticles. The mass ratio of the added crosslinking agent CaCl2 to FA-CMCS-Ce6 is 1:5, and the mass ratio of DOX dosage to FA-CMCS-Ce6 is 1:10.

[0030] figure 1 It is a schematic diagram of synthesis and preparation of DOX / FA-CMCS-Ce6 nanopa...

Embodiment 3

[0032] Example 3: In vitro drug release of DOX / FA-CMCS-Ce6 nanoparticles

[0033] Add DOX solution and DOX / FA-CMCS-Ce6 nanoparticles (both at a concentration of 1 mg / ml of DOX) to phosphate buffer at pH 7.4 (50 μmol / L) and transfer to a dialysis tube (molecular weight cut-off 1 kDa ), place the dialysis tube in 10 ml of phosphate buffer, and place it in a constant temperature shaker (50 rpm) at 37°C to measure the release. At the designated time point, the solution outside the dialysis tube was taken, and an equal volume of fresh buffer solution was added at the same time, and the content of doxorubicin was determined by ultraviolet spectrophotometry.

[0034] Figure 4 It is the result of in vitro release of doxorubicin. When the pH of the release medium is 5.5 and 7.4, the release has a burst release phenomenon, which is mainly caused by the drug adsorbed on the outer layer of the nanoparticles. After 2 hours, the release of the carrier drug enters the slow and controlled ...

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Abstract

The invention discloses a tumor-targeted nanometer drug delivery system for cooperative chemotherapy and photodynamic therapy and a preparation method thereof. The drug delivery system is prepared from carboxymethyl chitosan, folate, a photosensitizer chlorine e6 and adriamycin, wherein the chlorine e6 and the folate are coupled to a carboxymethyl chitosan chain segment through an amido bond, and are loaded to polymer nanoparticles of the adriamycin through an ion exchange method. The nanometer material prepared by the method is high in yield, regular in shape and even in distribution. In-vivo and in-vitro experiments prove that the tumor targeting property of the nanometer preparation can be significantly improved by folate receptor mediation; enrichment on the tumor part is achieved and drug release is controlled. The photosensitizer is capable of effectively reversing the chemotherapy drug resistance and significantly inhibiting the growth of tumors after being irradiated by near-infrared light. Therefore, the related nanometer drug delivery system has good application prospect in the aspect of breast cancer treatment.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a drug delivery system which has a targeting effect on tumors and has both tumor chemotherapy and photodynamic therapy and its application. Background technique [0002] Chemotherapy occupies a very important position in tumor treatment, but due to the lack of selectivity of chemotherapeutic drugs in the body and the multi-drug resistance of tumor cells, it leads to obvious toxic and side effects, which is difficult for patients to tolerate, and at the same time limits the dosage, resulting in the cost of general chemotherapy. The effect is poor. Therefore, enhancing the tumor targeting of chemotherapeutic drugs and improving the chemotherapeutic sensitivity of drugs to tumor cells is the key to improving the effect of tumor chemotherapy. [0003] At present, the combination of chemotherapy and other strategies is a novel and cutting-edge tumor treatment plan, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/48A61K31/704A61P35/00A61K47/69
CPCA61K31/704A61K41/0071
Inventor 张岩李洪仁孙弘李枚枚李锋
Owner SHENYANG UNIV
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