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Dual target liposome and preparation method and application thereof

A technology for targeting liposomes and liposomes, which can be used in liposome delivery, pharmaceutical formulations, medical preparations with inactive ingredients, etc. Ability, drug concentration increase, effect of enhancing effect

Inactive Publication Date: 2010-09-01
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mainly the following two reasons limit the effect of chemotherapy: antineoplastic drugs cannot penetrate the blood-brain barrier and their ability to penetrate the tumor tissue after passing through the blood-brain barrier is very poor

Method used

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  • Dual target liposome and preparation method and application thereof
  • Dual target liposome and preparation method and application thereof
  • Dual target liposome and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Embodiment 1, the preparation of liposome

[0049] Lecithin (EPC) and polyethylene glycol-distearoylphosphatidylethanolamine (polyethylene glycol-distearoylphosphatidylethanolamine, PEG2000-DSPE) were purchased from Japan Oil Co., Ltd. (Japan NOF Company); cholesterol (cholesterol) was purchased from Haidian District, Beijing Microbial culture medium product factory (Beijing Shuangxuan microbial culture medium product factory); DSPE-PEG2000-COOH, DSPE-PEG2000-NH 2 , p-aminophenyl-α-D-manno-pyranoside (MAN), transferrin (molecular weight 80,000) (holo-transferrin, TF) were purchased from Sigma-Aldrich Corporation, Beijing local agent, China; shephedex G-100, Trinitrobenzene sulphonic acid (TNBS) was purchased from Sigma-Aldrich Company, Beijing local agent, China;

[0050] 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDCI) was purchased from Shanghai Medpep Co., Ltd., China; N-hydroxysuccinimide (NHS) was purchased from Beijing Sansheng Tengda Technolog...

Embodiment 2

[0073] Embodiment 2, the performance measurement of liposome

[0074] 1. Determination of transferrin modification rate (BCA method)

[0075] 1. Preparation of standard curve

[0076] The BCA kit (Pierce Corporation, Beijing local agent, China) was used to measure BSA as a standard, and 0, 25, 125, 250, 500, 750 and 1000 μg / ml BSA was prepared with PBS, and after adding the working solution, it was kept at 37°C Incubate for 30 min, cool to room temperature and measure absorbance at 540 nm. Standard curve see figure 2 .

[0077] 2. Modification rate

[0078] Measure the content of transferrin in liposome C and liposome D prepared by BCA kit instructions, and calculate the modification rate (μg TF / μmol phospholipid) (modification rate=connected to the transferrin on the liposome) Ferritin amount: the amount of lecithin), the results are shown in Table 2.

[0079] Transferrin content and transferrin modification rate (n=3) in the liposome of table 2

[0080]

[0081] 2...

Embodiment 3

[0094] Embodiment 3, liposome dual targeting effect evaluation in vitro

[0095] The mouse C6 glioma cell line was purchased from the Institute of Materia Medica, Chinese Academy of Medical Sciences; Ham's F10 medium was purchased from GIBCO / BRL (Germany) Beijing agent Beijing Maicheng Technology Co., Ltd.; fetal bovine serum (FBS) was purchased from Sino-US joint venture Lanzhou Min Hai Biological Engineering Co., Ltd.; horse serum was purchased from Beijing Baierdi Biotechnology Co., Ltd.; SRB was purchased from Sigma Beijing Agent Baierdi Biotechnology Co., Ltd.; >250U·mg -1 ), mouse brain endothelial cells (brainmicrovascular endothelial cells, BMVEC) and endothelial cell culture medium (cndothclial cell culture medium, ECCM) were purchased from the Clinical Research Institute of China-Japan Friendship Hospital; microplate reader (BIO-RAD Model 680, Shanghai, China Bio-Rad Laboratory Equipment Company), Cell Inserter (Corning, USA); Resistance Meter, (EVOMk, Word Precisio...

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Abstract

The invention discloses a dual target liposome and a preparation method and application thereof. The target liposome provided by the invention consists of liposome and modifiers on the surface of the liposome, wherein the modifiers on the surface of the liposome comprise p-aminophenyl-alpha-D-manno-pyranoside and transferrin. The invention also discloses a medicament-loaded liposome, which is obtained by wrapping daunorubicin by using the target liposome. The obtained target liposome has good capability of crossing the blood brain barrier, targets brain glioma, and can be used as a medicament carrier. The medicament-loaded liposome can target the medicament to a brain glioma site after crossing the blood brain barrier so as to greatly increase the concentration of the medicament at a tumor site and improve the effect of chemotherapy. The target liposome provides a new measure for brain glioma chemotherapy, contributes to the research of non-invasive therapy of the brain glioma, and has important theoretical meaning and clinical meaning.

Description

technical field [0001] The invention relates to a dual targeting liposome and its preparation method and application. Background technique [0002] Primary brain tumors have become one of the top ten causes of cancer death. Five to ten out of 100,000 people suffer from malignant glioma [Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol. 2002 Oct ;4(4):278-99. Behin A, Hoang-Xuan K, Carpentier AF, Delattre JY. Primary brain tumors in adults. Lancet. 2003 Jan 25;361(9354):323-31.]. Invasive glioma cells can rapidly infiltrate and destroy normal brain tissue structures, making it impossible to completely remove the tumor by surgery. Despite combined surgical resection, radiotherapy, and chemotherapy, the average survival time of patients with malignant glioma is less than one year [Astner ST, Pihusch R, Nieder C, Rachinger W, Lohner H, Tonn JC, Molls M, Grosu AL. Extensive local and...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/42A61K31/704A61P35/00A61K47/24A61K47/28A61K47/34
Inventor 吕万良应雪温禾杜举
Owner PEKING UNIV
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