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Targeted fluorescent liposome based on low-frequency ultrasonic response, preparation method of liposome and application

A liposome and fluorescence technology, applied in the directions of liposome delivery, echo/ultrasonic imaging agents, preparations for in vivo tests, etc., can solve the problem of lack of timely feedback of therapeutic effects, difficult control of drug release temperature, and drug aggregation. The degree of control cannot be monitored, etc., to achieve the effect of convenient industrial production, low toxicity and high drug loading rate

Inactive Publication Date: 2018-11-27
GUANGDONG NO 2 PROVINCIAL PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, patients have poor compliance with articular cavity puncture, and RA often has polyarticular lesions, making articular cavity puncture more difficult and increasing the chance of joint cavity infection
In order to achieve the effect of avoiding intra-articular puncture injection and increasing the local concentration of drugs, some scholars have constructed MTX-loaded gold nanoparticles, which can be accumulated in the lesion through the passive retention effect of nanoparticles after intravenous injection. , combined with laser-promoted drug release for RA treatment, and achieved good results; however, during the treatment process, the temperature at which the photothermal effect promotes drug release is difficult to control, the degree of drug aggregation cannot be monitored, and the therapeutic effect cannot be given timely feedback.

Method used

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  • Targeted fluorescent liposome based on low-frequency ultrasonic response, preparation method of liposome and application
  • Targeted fluorescent liposome based on low-frequency ultrasonic response, preparation method of liposome and application
  • Targeted fluorescent liposome based on low-frequency ultrasonic response, preparation method of liposome and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 Preparation of integrated diagnosis and treatment targeting fluorescent MTX-loaded acoustic liposomes

[0040] (1) Synthesis of DSPE-PEG-iRGD: put free iRGD and DSPE-PEG-Maleimide in ultrapure water at a molar ratio of 1.5:1, and use a rotor (200r / min) was fully stirred for 24 hours, then the reaction solution was dialyzed in a dialysis bag (MWCO: 3500) for 48 hours to filter out impurities, and finally the dialyzed reaction solution was transferred to a vial with a pipette gun and placed in -80°C refrigerator, after freezing, place the vial in freeze-drying for 48 hours to finally synthesize DSPE-PEG-iRGD, freeze-dry and place in -20°C refrigerator for later use.

[0041] (2) Preparation of iRGD cyclopeptide-modified low-frequency ultrasound-responsive targeted fluorescence-loaded MTX acoustic liposomes by combining thin film hydration method and freeze-drying method: DPPC, CHO, DSPE-PEG and spare DSPE-PEG-iRGD were used respectively Dissolve chloroform, an...

Embodiment 2

[0042] Example 2 Basic characterization and in vitro performance testing of targeted fluorescent MTX acoustic liposomes

[0043] (1) Morphological characteristics of iELPs by transmission electron microscope and Malvern particle size analyzer ( figure 1 B) and particle size ( figure 1 C) Determination is carried out, and the results show that the targeted nanoacoustic liposome is a spherical structure of (111.73 ± 3.5) nm;

[0044] (2) In order to analyze the low-frequency ultrasonic response performance of iELPs, the inventors measured the ultrasonic controlled release ability of targeted nanoacoustic liposomes. The results showed that the drug release of iELPs increased with the increase of ultrasonic intensity and ultrasonic irradiation time. increase( figure 1 D / 1E).

[0045] (3) In order to analyze the targeting performance of targeted acoustic liposomes, the inventors verified the targeting performance of targeted acoustic liposomes through high-expression αvβ3 cells ...

Embodiment 3

[0046] Example 3 Targeted Fluorescence-loaded MTX Acoustic Liposomes for Guided Treatment of RA

[0047] 1. Construction of RA animal model

[0048] The 1:1 mixed emulsion of bovine type II collagen and Freund's adjuvant (including complete Freund's adjuvant and incomplete Freund's adjuvant) was injected subcutaneously into the base of the tail of 8-week-old DBA / 1J mice, and the immune process was divided into For two steps, the second immunization was carried out on the 21st day after the first immunization to establish the RA animal model. Among them, the first immune induction is to subcutaneously inject the mixture of bovine type II collagen and complete Freund's adjuvant at the base of the tail of DAB / 1J mice, each 0.1ml; the second immune induction is to inject the mixture of DAB / 1J mice at different positions Subcutaneous injection of bovine type II collagen and incomplete Freund's adjuvant mixture, each 0.1ml. The model was evaluated according to the Arthritis Index ...

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Abstract

The invention provides a targeted fluorescent liposome based on low-frequency ultrasonic response, a preparation method of the liposome and an application, and particularly provides an active targeting medicine carrying fluorescent acoustic liposome which comprises a bimolecular lamellar lipid membrane, medicines and fluorescent agents, wherein the bimolecular lamellar lipid membrane comprises dipalmitoyl phosphatidyl choline (DPPC), cholesterol (CHO), polyethylene glycol modified distearoyl phosphoethanolamine (DSPE-PEG) and (DSPE-PEG-iRGD), and the acoustic liposome wraps the medicines and the fluorescent agents. The medicines are selected from methotrexate (MTX), the fluorescent agents are selected from indocyanine green (ICG), and polyethylene glycol (PEG) in the polyethylene glycol modified distearoyl phosphoethanolamine (DSPE-PEG) is selected from PEG1000-PEG3000.

Description

technical field [0001] The invention belongs to the field of medical diagnosis and treatment, and in particular relates to a low-frequency ultrasonic response-based integrated fluorescent liposome for diagnosis and treatment of rheumatoid arthritis and a preparation method thereof. Background technique [0002] Rheumatoid arthritis (RA) is a highly disabling autoimmune disease with synovitis, pannus neogenesis, and bone destruction as the basic pathological changes. Side effects such as liver function damage and bone marrow suppression often lead to the cessation of clinical intervention and the development of refractory RA. How to improve the treatment method and optimize the treatment method, so as to increase the concentration of MTX drug in RA diseased joints, enhance the therapeutic effect of MTX, and reduce systemic side effects at the same time, is a difficult problem in the treatment of RA. [0003] With the deepening understanding of the side effects of RA medicati...

Claims

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Application Information

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IPC IPC(8): A61K49/22A61K31/519A61K47/54A61K47/62A61K47/69A61K49/00A61P19/02A61P29/00
CPCA61K31/519A61K49/0034A61K49/221A61K49/227A61K47/542A61K47/62A61K47/6911A61P19/02A61P29/00
Inventor 刘红梅吴昊晗武昊甘珍
Owner GUANGDONG NO 2 PROVINCIAL PEOPLES HOSPITAL
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