Drug delivery system formed by ligand polypeptide ph1 and its application

A delivery system and drug technology, applied in liposome delivery, drug combination, antineoplastic drugs, etc., can solve the problems of poor prognosis and easy recurrence, achieve great medical practicability, inhibit tumor recurrence, and inhibit tumor cells proliferating effect

Active Publication Date: 2018-07-31
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the traditional drug treatment for tumor cells often has a poor prognosis and is prone to recurrence, which has an important role in the existence of tumor-associated macrophages.

Method used

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  • Drug delivery system formed by ligand polypeptide ph1 and its application
  • Drug delivery system formed by ligand polypeptide ph1 and its application
  • Drug delivery system formed by ligand polypeptide ph1 and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1, the synthesis of PH1 polypeptide lipid

[0048] Hydrogenated soybean lecithin (HSPC) and 1,2-distearoylphosphatidylethanolamine 2000-maleate (DSPE-PEG2000-Mal) were purchased from NOF Corporation;

[0049] PH1 polypeptide was purchased from Shanghai Jier Biochemical Co., Ltd.; other reagents were purchased from China Sinopharm Chemical Reagent Company;

[0050] All-trans retinoic acid (ATRA) was purchased from Sigma, USA;

[0051] Step 1. Synthesis of PH1 polypeptide lipid (DSPE-PEG2000-Mal-PH1)

[0052] (1) Preparation of degassed HEPES solution: 50ml of ultra-pure H2O was heated and boiled for 10min, filled with N2 and saturated to cool, then 595.75mg of HEPES salt was added to obtain a concentration of 50mM, and the pH was adjusted to 7.0 with 2mol / L NaOH, and the whole process was protected by N2. Store at 4°C for later use;

[0053] (2) Weigh 10 mg of DSPE-PEG2000-MAL powder, add 10 ml of degassed HEPES salt hydrated lipid film to form a micellar...

Embodiment 2

[0061] Example 2. Preparation and identification of the complex of all-trans retinoic acid polypeptide liposomes

[0062] Egg lecithin (EPC) was purchased from NOF Corporation, Lot No: 108057-3;

[0063] Cholesterol and PEGylated phospholipid 1,2-monostearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) were purchased from Avanti Polar Lipids, USA;

[0064] Step 1. Preparation of all-trans retinoic acid and polypeptide liposome complex

[0065] Lipid ratio in eight liposome formulations (shown in Table 2): egg yolk lecithin (EPC): cholesterol (Chol): polypeptide lipid: PEGylated phospholipid 1,2-monodistearoylphosphatidyl Ethanolamine-polyethylene glycol 2000 (DSPE-PEG2000);

[0066] Table 2

[0067] prescription

Composition Molar Ratio

2%PEG

ATRA:EPC:CHOL:DSPE-PEG2000=3:15:10:0.52

4%PEG

ATRA:EPC:CHOL:DSPE-PEG2000=3.3:15:10:1

NON-ATRA

PH1:EPC:CHOL:DSPE-PEG2000=0.52:15:10:0.52

2%PH1+2%PEG

ATRA:PH1:...

Embodiment 3

[0079] Example 3. In vitro and in vivo binding test of polypeptide liposomes and tumor-associated macrophages (TAMs)

[0080] Egg lecithin (EPC) was purchased from NOF Corporation, Lot No: 108057-3;

[0081] Cholesterol and PEGylated phospholipid 1,2-monostearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) were purchased from Avanti Polar Lipids, USA;

[0082] Fluorescent lipid FITC DHPE was purchased from American Invitrogen Company

[0083] Polypeptide lipid (DSPE-PEG2000-maleimid-PH1) self-synthesized;

[0084] Anti-mouse FITC-CD11b antibody, Anti-mouse PE-Gr1 antibody, Anti-mouse Percp / cy5.5-F4 / 80 antibody, Anti-mouse FITC-CD11b antibody and its isotype control antibody were all purchased from ebiociecce, USA;

[0085] Step 1. Inoculate the tumor

[0086] 1x106 4T-1 cells were trypsinized and resuspended in 200 μL of PBS buffer; the tumor cell suspension was injected subcutaneously in the mammary gland of 6-week-old Balb / c mice; after 2 weeks, the ...

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Abstract

The present invention relates to a drug delivery system formed by a ligand polypeptide PH1 and its application. The drug delivery system includes a ligand polypeptide PH1, a drug-loading system, and at least one active substance, and the polypeptide PH1 is connected to the drug-loading system. Surface; the present invention also relates to the use of the ligand polypeptide PH1 in the preparation of drugs specifically binding to tumor-associated macrophages. Through long-term experiments, it has been found and proved that PH1 polypeptide can target tumor-related cells well, induce its differentiation and inhibit tumor growth. The complex of PH1 polypeptide liposome can target tumor-related macrophages well, and can be applied to small The targeted delivery of molecular drugs and gene drugs to tumor-associated macrophages, the all-trans retinoic acid polypeptide liposome in the present invention can effectively induce the differentiation of tumor-associated macrophages and inhibit the growth of tumors, and can be applied to inhibit tumors cell proliferation and tumor recurrence, and thus have great medical utility.

Description

technical field [0001] The invention relates to a targeted polypeptide liposome preparation and its application, in particular to a drug delivery system formed by ligand polypeptide PH1 and its application. Background technique [0002] In many years of clinical practice, it has been observed that there are often a large number of inflammatory cell infiltration in the tumor tissue of tumor patients, but its biological significance has only been paid attention to by the academic community in recent years: these tumor-associated inflammatory cells are considered to be important for tumor growth. , survival, and metastasis have an important role in promoting. [0003] The source of tumor-associated inflammatory cells is considered to be lymphoid precursor cells (Myeloid cells) from the bone marrow. In normal tissues, these myeloid-derived precursor cells can quickly differentiate into granulocytes, macrophages, and dendritic cells, etc., but under disease conditions such as tu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/42A61K31/203A61K9/127A61P35/00
Inventor 徐宇虹吴烈宜司晓菲
Owner SHANGHAI JIAO TONG UNIV
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