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Polymer vesicle of double-loading anthracycline ring medicine and photosensitizer, having bubble generation function, as well as preparation

A technology of polymers and anthracyclines, which is applied in the field of polymer vesicles and preparations of double-loaded anthracyclines and photosensitizers with bubble generation function to achieve good biocompatibility

Active Publication Date: 2018-10-16
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the PCL- b -PEG- b -PCL polymersomes have not been reported yet

Method used

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  • Polymer vesicle of double-loading anthracycline ring medicine and photosensitizer, having bubble generation function, as well as preparation
  • Polymer vesicle of double-loading anthracycline ring medicine and photosensitizer, having bubble generation function, as well as preparation
  • Polymer vesicle of double-loading anthracycline ring medicine and photosensitizer, having bubble generation function, as well as preparation

Examples

Experimental program
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Effect test

Embodiment 1

[0036] A method for preparing double-loaded doxorubicin and indocyanine green pH / temperature dual-sensitive polymer vesicles with bubble generation function, comprising the following steps:

[0037] (1) the PCL 8000 - b -PEG 8000 - b -PCL 8000 The amphiphilic tri-block copolymer and indocyanine green transhydrophobic were dissolved in dichloromethane, and the dichloromethane was removed by rotary evaporation in a rotary evaporator, and a uniform film was formed on the inner wall of the reactor, and the vacuum was removed overnight. Residual organic solvents;

[0038] (2) Add 5 mL of 300 mM ammonium bicarbonate aqueous solution into the reactor, the PCL 8000 - b -PEG 8000 - b -PCL 8000 The ratio of amphiphilic triblock copolymer to ammonium bicarbonate aqueous solution was 4 mg:1 mL, hydrated at 65 °C for 5 h, oscillated and mixed, placed at room temperature, and ultrasonicated for 30 min in an ice bath to obtain a stable single-loaded Polymersome dispersion of indocy...

Embodiment 2

[0044] Characterization of BG-DIPS with bubble generation function.

[0045] The BG-DIPS solution prepared in Example 1 was diluted with PBS pH 7.4 and dropped onto a carbon-coated copper grid. After drying, it was placed under a transmission electron microscope to observe the morphology of polymer vesicles with bubble generation function. Transmission electron microscope (TEM) photographs as figure 2 , A), it can be clearly observed that bubbles are formed in the vesicles. With the extension of the observation time, the bubbles absorb the energy of the electron beam and merge into large bubbles, but the formed large bubbles will not destroy the structure of the vesicles. At the same time, it can be clearly observed that the vesicles have obvious membrane structure.

[0046] The BG-DIPS solution prepared in Example 1 was diluted with PBS pH7.4 and PBS pH5.5 respectively, and then dropped onto the carbon film copper grid. -DIPS was irradiated with 1 W / cm2 808nm laser for 5mi...

Embodiment 3

[0048] Determination of in vitro release behavior of BG-DIPS with bubble generating function.

[0049] Take the BG-DIPS solution prepared in Example 1 and place it in a dialysis bag to seal it, then place the dialysis bag in 15 mL of pH7.4 PBS solution or pH5.5 PBS solution, and set up laser irradiation groups at the same time, each parallel to 3 groups, The in vitro release experiment was carried out under the condition of constant temperature of 37°C and shaking frequency of 120 times / min. Take out all the released liquid regularly and measure the absorbance of doxorubicin by UV-Vis spectrophotometer and supplement the same volume of PBS buffer solution. The result is as image 3 Shown, drug release amount: PBS pH7.4 group<PBS pH5.5 group<PBS pH7.4 plus laser group<PBS pH5.5 plus laser group. The results showed that the release rate of doxorubicin from vesicles was much faster under acidic conditions (pH5.5) than at physiological pH (7.4). It shows that the drug-loaded po...

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Abstract

The invention relates to a polymer vesicle of a double-loading anthracycline ring medicine and a photosensitizer, having a bubble generation function, as well as preparation. A pH / temperature double-sensitive multifunctional polymer vesicle of hydrophilic inner cavity loaded anthracycline ring medicine and a hydrophobic film loaded photosensitizer, having the bubble generation function, is prepared by taking an amphiphilic triblock copolymer PCL-b-PEG-b-PCL as a material. The anthracycline ring medicine is wrapped with and loaded in the hydrophilic inner cavity by an ammonium hydrogen carbonate gradient active medicine loading method, ammonium hydrogen carbonate can be decomposed under the condition of low pH value or heating to generate carbon dioxide bubbles, the structure of the vesicleis broken and the wrapped medicines are released rapidly. After the medicines are delivered to the local part of tumor through EPR (enhanced permeability and retention) targeting, the therapeutic effect of the anthracene ring chemotherapeutic medicines on the tumor can be obviously improved under illumination. The polymer vesicle can serve as a medicine carrier to wrap and load hydrophilic and hydrophobic medicines simultaneously, has a stable structure, has high biocompatibility and degradability, and has a wide application prospect on the aspects of medicine delivery and controllable release and chemotherapeutic combined photothermal therapy on the tumor.

Description

technical field [0001] The present invention relates to a polymer vesicle and preparation of a double-loaded anthracycline drug and a photosensitizer with the function of generating bubbles, in particular to a hydrophilic cavity-loaded anthracycline drug and a hydrophobic film layer with the function of generating bubbles Preparation and application of pH / temperature dual-sensitive multifunctional polymersomes loaded with photosensitizers. Background technique [0002] In recent decades, the incidence of malignant tumors has become higher and higher, and the age of onset is gradually decreasing, which seriously threatens human life and health. Chemotherapy is one of the most commonly used tumor treatment methods in clinical practice. With the in-depth research on the mechanism of chemotherapy drugs in recent years, the level of clinical tumor treatment has been greatly improved. Despite this, chemotherapy drugs have relatively large side effects, causing irreversible damage...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/127A61K47/34A61P35/00A61K31/136A61K31/704
CPCA61K9/1273A61K31/136A61K31/704A61K41/0057A61K41/0071A61K47/34A61P35/00A61K2300/00
Inventor 朱敦皖张琳华樊帆秦玉黄晨露
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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