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A preparation method of targeted temperature-controlled silibinin-loaded thermosensitive liposome-microbubble complex drug delivery system

A technology of drug delivery system and liposome, which is applied in the field of preparation of silibinin-loaded thermosensitive liposome-microbubble complex drug delivery system, which can solve the problems of tumor residue and achieve high-efficiency release and good temperature control The effect of the characteristic

Inactive Publication Date: 2017-03-15
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the influence of the blood supply in the tissue and the location of the tumor, the local temperature may drop to form a sub-high temperature field (40-60°C), resulting in residual tumor

Method used

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  • A preparation method of targeted temperature-controlled silibinin-loaded thermosensitive liposome-microbubble complex drug delivery system

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] 1) Preparation of silibinin-loaded thermosensitive liposomes

[0027] 30mg monopalmitoylphosphatidylcholine (DPPC), 3mg dipalmitoylphosphatidylcholine (MPPC), 5mg distearoylphosphatidylethanolamine-polyethylene glycol-amino (DSPE-PEG2000-Amine) and 2mg water Silybin was dissolved in 5mL of absolute ethanol to obtain a raw material solution. The raw material solution was prepared into a thin film with a rotary evaporator at 25° C. (formed in 1000mL water) dissolved film, and then after ultrasonic dispersion, microporous membrane filtration, phosphate buffer dialysis to obtain a solution containing water-loaded silibinin thermosensitive liposomes; wherein ultrasonic dispersion is in an ice bath The ultrasonic power was 100W, and the ultrasonic time was 10min; the microporous membrane filtration was performed three times with microporous membranes with a pore size of 0.8 μm and 0.4 μm; The solution is dialysate, which is changed every 8 hours and dialyzed for 48 hours to ...

Embodiment 2

[0033] 1) Preparation of silibinin-loaded thermosensitive liposomes

[0034] 20mg monopalmitoylphosphatidylcholine (DPPC), 2mg dipalmitoylphosphatidylcholine (MPPC), 3mg distearoylphosphatidylethanolamine-polyethylene glycol-amino (DSPE-PEG2000-Amine) and 3mg water Silybin was dissolved in 6mL of absolute ethanol to obtain a raw material solution. The raw material solution was prepared into a thin film with a rotary evaporator at 20° C. (formed in 1000mL water) dissolved film, and then after ultrasonic dispersion, microporous membrane filtration, phosphate buffer dialysis to obtain a solution containing water-loaded silibinin thermosensitive liposomes; wherein ultrasonic dispersion is in an ice bath The ultrasonic power was 80W, and the ultrasonic time was 5min; the microporous membrane filtration was performed three times with microporous membranes with a pore size of 0.6 μm and 0.2 μm; The solution is dialysate, which is changed every 4 hours and dialyzed for 72 hours to re...

Embodiment 3

[0040] 1) Preparation of silibinin-loaded thermosensitive liposomes

[0041] Mix 50mg monopalmitoylphosphatidylcholine (DPPC), 8mg dipalmitoylphosphatidylcholine (MPPC), 8mg distearoylphosphatidylethanolamine-polyethylene glycol-amino (DSPE-PEG2000-Amine) and 10mg water Silybin was dissolved in 20mL of absolute ethanol to obtain a raw material solution. The raw material solution was prepared into a film with a rotary evaporator at 30° C. (formed in 1000mL water) dissolved film, and then after ultrasonic dispersion, microporous membrane filtration, phosphate buffer dialysis to obtain a solution containing water-loaded silibinin thermosensitive liposomes; wherein ultrasonic dispersion is in an ice bath The ultrasonic power was 120W, and the ultrasonic time was 15min; the microporous membrane filtration was performed three times with microporous membranes with a pore size of 0.7 μm and 0.3 μm; The solution is dialysate, which is changed every 10 hours and dialyzed for 60 hours t...

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Abstract

The invention provides a preparation method of a targeted temperature-controlled water-loading silibinin temperature-sensitive lipidosome-microbubble complex drug delivery system. The preparation method comprises the following steps of with single-palmitoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline, distearoyl phosphatidyl ethanolamine-polyethylene glycol-amino and silibinin as raw materials, preparing water-loading silibinin temperature-sensitive lipidosome by virtue of a membrane rotary evaporation method; and coupling the water-loading silibinin temperature-sensitive lipidosome with an ultrasonic contrast agent, namely SonoVue microbubble, so as to prepare the targeted temperature-controlled water-loading silibinin temperature-sensitive lipidosome-microbubble complex drug delivery system. According to the preparation method, a new drug delivery system is established by combining the temperature-sensitive lipidosome with the microbubble; the efficient release of local tissues of a drug at a sub-high temperature field are achieved by virtue of the targeted explosion of the microbubble and the local temperature control effect of the temperature-sensitive lipidosome, so that the bioavailability of the drug is improved, and furthermore, residual tumors during thermal ablation treatment are reduced.

Description

technical field [0001] The invention belongs to the field of targeted temperature-controlled drug delivery systems, and in particular relates to a preparation method of a targeted temperature-controlled thermosensitive liposome-microbubble complex drug delivery system loaded with silibinin. Background technique [0002] Silibinin is an anti-inflammatory and anti-oxidant hepatoprotective drug widely used clinically in recent years, and it is also considered to be able to significantly change the inflammatory microenvironment of tumors, thereby inhibiting tumor growth. However, at present, silibinin has low water-solubility and fat-solubility, poor oral absorption, low bioavailability, poor tissue permeability, and its absorption and utilization are still problems to be solved. Ultrasound-guided thermal ablation therapy for tumors, such as radiofrequency, microwave, and high-intensity focused ultrasound, achieves the purpose of causing tumor necrosis by causing the temperature...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/00A61K9/127A61K31/357A61P35/00
Inventor 罗文张云飞张邦乐周晓东巨佳
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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