Hyaluronic acid modified mitochondria target liposome and preparation method thereof

A hyaluronic acid modified and targeted liposome technology, which is applied in liposome delivery, medical preparations containing non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of paclitaxel’s anti-tumor effect, etc. Achieve the effect of avoiding systemic toxic and side effects, increasing drug concentration, and increasing circulation time

Active Publication Date: 2018-11-06
SHANGHAI INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, ordinary paclitaxel liposomes cannot target the tumor site, and due to the influence of multidrug resistance, the antitumor effect of paclitaxel has been greatly affected

Method used

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  • Hyaluronic acid modified mitochondria target liposome and preparation method thereof
  • Hyaluronic acid modified mitochondria target liposome and preparation method thereof
  • Hyaluronic acid modified mitochondria target liposome and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] A preparation method of hyaluronic acid-modified mitochondria-targeted paclitaxel liposomes

[0030] Dissolve egg yolk lecithin, cholesterol, paclitaxel and dequalinium chloride in a mixed solution of chloroform:methanol 1:1 according to the molar ratio of 95:5:10:20, evaporate to dryness with a rotary evaporator to form a thin film and continue vacuum drying 1h, then add 100ml of 0.02M phosphate buffer solution, hydrate in a water bath at 40°C, and disperse the lipid film evenly, and hydrate the liposomes at 40°C for 1h. The hydrated liposome suspension was passed through a film squeezer equipped with a 100nm polycarbonate film, and the film was squeezed 10 times at 50°C. The activated hyaluronic acid was added dropwise to the prepared liposomes at a mass ratio of 1:20, and reacted overnight in a shaker. The particle size, zeta and PDI of the sample were measured by a particle size analyzer, the paclitaxel concentration of the liposome was measured by high performance...

Embodiment 2

[0033] A preparation method of hyaluronic acid-modified mitochondria-targeted paclitaxel liposomes

[0034] Dissolve hydrogenated soybean phospholipid HSPC, dioleoylphosphatidylethanolamine DOPE, cholesterol, paclitaxel and dequalinium chloride in a mixed solution of chloroform:methanol 1:1 according to the molar ratio of 60:35:5:5:10, and use rotary evaporation Evaporate it into a thin film and continue vacuum drying for 1 hour, then add 100ml of 0.02M phosphate buffer solution, hydrate in a water bath at 40°C, and disperse the lipid film evenly, and hydrate the liposomes at 40°C for 1 hour. The hydrated liposome suspension was passed through a film squeezer equipped with a 100nm polycarbonate film, and the film was squeezed 10 times at 50°C. The activated hyaluronic acid was added dropwise to the prepared liposomes at a mass ratio of 1:20, and reacted overnight in a shaker. The particle size, zeta and PDI of the sample were measured by a particle size analyzer, the paclitax...

Embodiment 3

[0037] A preparation method of hyaluronic acid-modified mitochondria-targeted paclitaxel liposomes

[0038]Dissolve soybean lecithin, cholesterol, paclitaxel and dequalinium chloride in a mixed solution of chloroform:methanol 1:1 according to the molar ratio of 60:35:5:10:15, evaporate it to dryness with a rotary evaporator to form a thin film and keep vacuuming Dry for 1 hour, then add 100ml of 0.02M phosphate buffer solution, hydrate in a water bath at 40°C, and disperse the lipid film evenly, and hydrate the liposomes at 40°C for 1 hour. The hydrated liposome suspension was circulated 3 times at 300 bar at 50°C under the action of a homogenizer, and homogenized 10 times at 1100 bar. The activated hyaluronic acid was added dropwise to the prepared liposomes at a mass ratio of 1:20, and reacted overnight in a shaker. The particle size, zeta and PDI of the sample were measured by a particle size analyzer, the paclitaxel concentration of the liposome was measured by high perfo...

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Abstract

The invention discloses hyaluronic acid modified mitochondria target liposome and a preparation method thereof. The mitochondria target liposome disclosed by the invention is prepared from drug carrying liposome and outer-layer modifying hyaluronic acid, wherein the drug loading liposome is liposome covered by hydrophobic drug and dequalinium chloride, and the hydrophobic drug is any one chosen from adriamycin, taxol, 10-hydroxycamptothecine, irinotecan or cis-platinum. The hyaluronic acid modified mitochondria target liposome disclosed by the invention has the beneficial effects that receptors are effectively targeted, uptake of tumor cells to liposome is improved, cell mitochondria is further targeted in the tumor cells, a function of damaging the mitochondria is achieved, tumor cell apoptosis is promoted, tumor cell growth is inhibited, and ability of overcoming multidrug resistance of the tumor cells is achieved.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a hyaluronic acid-modified mitochondria-targeted liposome and a preparation method thereof. Background technique [0002] Cancer is one of the diseases that are difficult to cure in modern medicine. One of the important reasons is that the multidrug resistance of tumors greatly reduces the effect of antitumor drugs. In recent years, the targeted delivery of drugs in tumor cells is a rapidly developing field. Mitochondria are the organelles in tumor cells that guarantee cell energy metabolism and regulate cell apoptosis. Targeting mitochondria can promote cell apoptosis and effectively To effectively overcome the multidrug resistance of tumor cells and enhance the anti-tumor effect of drugs has gradually become a research direction to effectively overcome the multidrug resistance of tumor cells. [0003] Paclitaxel (PTX) is a natural drug with broa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/61A61K31/4709A61P35/00A61K31/337
CPCA61K9/0019A61K31/337A61K31/4709A61K47/61A61K47/6911A61P35/00A61K2300/00
Inventor 甘莉田永丰张华秦艳梅李东
Owner SHANGHAI INST OF TECH
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