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RSPO1-containing targeted drug delivery system, preparation and applications thereof

A targeted drug delivery and drug technology, applied in the direction of medical preparations containing active ingredients, antineoplastic drugs, drug combinations, etc., can solve problems such as taste disorders and weight loss

Active Publication Date: 2017-07-04
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the inhibition of the Wnt pathway by drugs inevitably causes many side effects, including muscle spasms, hair loss, taste disturbance, weight loss, etc.

Method used

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  • RSPO1-containing targeted drug delivery system, preparation and applications thereof
  • RSPO1-containing targeted drug delivery system, preparation and applications thereof
  • RSPO1-containing targeted drug delivery system, preparation and applications thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0114] The preparation of embodiment 1 RSPO1-PEG2000-DSPE

[0115] (1) Preparation of degassed HEPES solution: heat and boil ultrapure water, fill with N2 until saturated to cool, add HEPES salt to a concentration of 50mM, adjust pH to 7.0 with NaOH, and protect with N2 throughout the process;

[0116] (2) Weigh DSPE-PEG2000-MAL powder, add degassed HEPES salt solution, and hydrate into a micellar solution; add RSPO1 after TCEP reduction into the micellar solution under the protection of N2; Shaking at a constant temperature at 500 rpm, the final product RSPO1-PEG2000-DSPE was obtained after 24 hours of reaction.

[0117] For the results of polyacrylamide gel electrophoresis analysis, see figure 1 ,Such as figure 1 , showing that the band of RSPO1 protein after connecting DSPE-PEG2000 moved up ~3K, and the connection efficiency calculated by ImageJ was over 95%, which fully demonstrated the success of RSPO1-PEG2000-DSPE synthesis.

Embodiment 2

[0118] The preparation of the liposome of embodiment 2 RSPO1 modification

[0119] Liposomes were prepared with phospholipids, cholesterol, and DSPE-PEG2000 as raw materials, and the moles of each raw material HSPC (hydrogenated soybean phospholipid) / Chol (cholesterol) / DSPE-PEG2000 (polyethylene glycol-distearoylphosphatidylethanolamine complex) The ratio is 55:42:3. The specific method includes steps: according to the proportion, take each raw material and dissolve it in an appropriate amount of chloroform, remove the chloroform by rotary evaporation under reduced pressure in a water bath at 37°C to form a uniform lipid film, add 1ml of PBS buffer solution for hydration for 1 hour, and ultrasonically in a water bath; PEG-modified liposomes can be prepared first through 100nm and 80nm polycarbonate membranes.

[0120] Then add the RSPO1-PEG2000-DSPE obtained in Example 1 into the PEG-modified liposomes prepared above in this example, shake at a constant temperature at 37°C wi...

Embodiment 3

[0121] Example 3 Preparation of RSPO1-modified FITC-labeled liposomes and study on tumor cell targeting in vitro

[0122] (1) Preparation of FITC-labeled liposomes modified by RSPO1

[0123] Liposomes were prepared with phospholipids, cholesterol, DSPE-PEG2000, FITC-DHPE as raw materials, each raw material HSPC (hydrogenated soybean phospholipid) / Chol (cholesterol) / DSPE-PEG2000 (polyethylene glycol-distearoylphosphatidylethanolamine compound The molar ratio of ) / FITC-DHPE is 55:42:3:1. The specific method includes the steps: according to the proportion, take each raw material and dissolve it in an appropriate amount of chloroform, remove the chloroform by rotary evaporation under reduced pressure in a water bath at 37°C to form a uniform lipid film, add 1ml of PBS buffer solution for hydration for 1 hour, and ultrasonicate in a water bath; 100nm and 80nm polycarbonate membranes were used to obtain FITC-modified liposomes.

[0124]Add the RSPO1-PEG2000-DSPE obtained in Exampl...

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Abstract

The present invention belongs to the field of pharmaceutical preparations, and particularly relates to a RSPO1-containing targeted drug delivery system, preparation and applications thereof, wherein the RSPO1-containing targeted drug delivery system contains a RSPO1 conjugating carrier molecule, a drug and drug carrier particles, wherein RSPO1 is on the surface of the drug carrier particle. According to the present invention, the RSPO1-containing targeted drug delivery system can significantly improve the targeting property of the drug and the tumor treatment effect on the basis of the reduction of the toxic-side effects of the drug.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a targeted drug delivery system containing RSPO1 and its preparation and application. Background technique [0002] Traditional tumor drug therapy (chemotherapy) kills tumor cells and also kills normal cells in the body, so the toxic and side effects not only affect the therapeutic effect but even endanger the lives of patients. Therefore, in recent years, efforts have been made to improve the specificity of chemotherapy for tumor cells. In order to achieve this goal, scientists have tried many methods, including the use of drug carriers to target tumors to achieve the goal of improving efficacy and reducing side effects. [0003] The components of anti-tumor drug carriers are various, including proteins, lipids, inorganic materials, polymer materials, and composite materials of inorganic and polymer materials. Currently developed nanocarrier systems inclu...

Claims

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Application Information

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IPC IPC(8): A61K47/42A61K31/704A61K48/00A61K31/713A61P35/00
CPCA61K31/704A61K31/713A61K47/42
Inventor 徐宇虹曹婧安松柱
Owner SHANGHAI JIAO TONG UNIV
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