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Brain tumor multiple targeting drug delivery system of stability polypeptide mediated cross-barrier film

A stable and multiple technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as reducing the targeting efficiency of mediated drug delivery systems

Inactive Publication Date: 2017-01-18
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Considering the influence of the in vivo environment, especially the enzyme barrier of serum and BBB, on the stability of the targeting ligand, which may reduce the targeting efficiency of the drug delivery system, and the D-configuration polypeptide has the advantage of good resistance to enzymatic degradation, the present application The inventor of the previous work designed and synthesized a stable brain-targeted polypeptide molecule D CDX, which has high affinity with nicotinic acetylcholine receptors, can carry the drug delivery system to penetrate the blood-brain barrier and enter the brain

Method used

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  • Brain tumor multiple targeting drug delivery system of stability polypeptide mediated cross-barrier film
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  • Brain tumor multiple targeting drug delivery system of stability polypeptide mediated cross-barrier film

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1D

[0051] Example 1 D Serum Stability of CDX and c(RGDyK)

[0052] Will D CDX or c(RGDyK) was made into a 1mg / mL solution with PBS, 0.1mL was added to 0.9mL 50% rat serum, incubated at 37°C, 100μL of the reaction solution was taken out at each time point, and acetonitrile (containing 0.1% TFA ) to precipitate the protein in the serum, let stand at 4°C for 10 minutes, centrifuge at 12000r / min for 10 minutes, take 20 μL of the supernatant for qualitative and quantitative analysis by HPLC, the results are as follows figure 1 shown.

Embodiment 2

[0053] Example 2 D Hepatic lysosomal enzyme stability of CDX and c(RGDyK)

[0054] Take fresh rat liver, add 0.3M ice sucrose solution to homogenate, centrifuge at 700×g for 10min to remove cell debris, combine the supernatant and centrifuge again, collect the supernatant and centrifuge at 10000×g for 10min, collect the precipitate and add 20mL of 0.3M sucrose solution (containing 1mM CaCl 2) and mix well, incubate at 37°C for 5min, add 20mL of 50% Percoll, centrifuge at 10000×g for 10min, collect the precipitate, resuspend with 0.3M sucrose solution, then centrifuge at 10000×g for 10min, collect the precipitate, and wash twice After three times, finally the liver lysosome homogenate obtained was resuspended with 0.3M sucrose solution, aliquoted, and stored at -80°C for future use. The protein content was determined with a BCA kit (using BSA as a standard protein to make a standard curve);

[0055] Add 100 μL of 1 mg / mL liver lysosome homogenate and 100 μL of 1 mg / mL CDX or...

Embodiment 3

[0056] Example 3 D CDX-PEG 3400 -DSPE and c(RGDyK)-PEG 3400 -Synthesis and characterization of DSPE

[0057] Will D Dissolve CDX-Cys in 0.1M PBS solution (pH7.2), take Mal-PEG 3400 -DSPE is dissolved in DMF, the two are mixed and then reacted with magnetic stirring, monitored by HPLC, and the reaction is stopped after the reaction of Mal-PEG-DSPE is complete, and the excess D CDX-Cys and DMF were dialyzed (molecular weight cut-off 3.5kDa) to remove, freeze-dried to obtain D CDX-PEG 3400 - DSPE, NMR characterizes its structure. Combine c(RGDyK)-Cys with Mal-PEG 3400 -DSPE is reacted as above to obtain c(RGDyK)-PEG 3400 -DSPE, NMR characterizes its structure (such as image 3 shown).

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Abstract

The invention belongs to the field of pharmacy, and relates to a brain tumor multiple targeting drug delivery system of a stability polypeptide mediated cross-barrier film, which is composed of stability polypeptide DCDX and c(RGDyK) and liposome. The drug delivery system is can resist an endogenous enzyme barrier and mediate cross-blood cerebral barrier (BBB) and blood-brain tumor barrier(BBTB). The experiment result displays that the liposome can delivers an entrapment model medicine to a target tissue, survival stage of the glioma model animal can be prolonged by the entrapment doxorubicin, and the curative effect of the medicine can be obviously increased. The brain tumor multiple targeting drug delivery system has good application prospect on diagnosis and treatment of brain tumor.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a liposome carrier system for multiple targeted drug delivery modified by a stable polypeptide, in particular to a stable polypeptide D The amino acid sequence of CDX is G D R D E. D I D R D TG D R D A D E. D R D W D S D E. D K D F and c (RGDyK) co-modified brain tumor targeting liposome carrier system against in vivo enzyme barrier, crossing blood-brain barrier and blood-brain tumor barrier, preparation method and its application in the preparation of brain tumor diagnosis and treatment drugs use. Background technique [0002] Studies have reported that in current clinical practice, the treatment of brain tumors is mainly surgical resection, supplemented by radiotherapy and chemotherapy. The five-year survival rate of patients is low, and brain tumors seriously threaten human health and life. Studies have shown that the brain, as the center of the human body, has many forbid...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/42A61P35/00A61K49/14A61K49/00A61K48/00A61K31/704
Inventor 陆伟跃魏晓丽占昌友谢操
Owner FUDAN UNIV
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