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Method for preparing mono-disperse microemulsion, liposome and microsphere based on microfluidic technology

A monodisperse, microfluidic chip technology, applied in biochemical equipment and methods, liposome delivery, emulsion delivery, etc., can solve the problems of ununiform size, poor repeatability, and low target encapsulation rate. Good repeatability and uniform size

Inactive Publication Date: 2011-05-25
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

By introducing drugs, enzymes, and cells into droplets, monodisperse microemulsions, liposomes, and biodegradable microspheres are produced, which solves the problems of unbalanced size, low target encapsulation rate, and poor repeatability in traditional preparation methods, in order to construct One that can control drug release, improve drug bioavailability, maintain enzyme and cell biological activity, improve drug carrier targeting, reduce drug systemic toxicity, and immunosuppressive and alloallergic reactions during cell transplantation, etc.

Method used

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  • Method for preparing mono-disperse microemulsion, liposome and microsphere based on microfluidic technology
  • Method for preparing mono-disperse microemulsion, liposome and microsphere based on microfluidic technology
  • Method for preparing mono-disperse microemulsion, liposome and microsphere based on microfluidic technology

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preparation example Construction

[0042] (2) Preparation of dispersed phase and continuous phase: dissolve fat-soluble drug paclitaxel and polylactic acid in chloroform (oil phase) as dispersed phase; dissolve polyvinyl alcohol or other water-soluble emulsifiers in water (water phase) as continuous phase; in figure 1 In the shown microfluidic chip device (the channel is modified by hydrophilicity), the dispersed phase is passed into channel 1 through the pump, the continuous phase is passed into channels 2 and 3, and the monodisperse O / W microemulsion ( or droplets); when water-soluble drugs are to be embedded, the water-soluble drug solution can be used as dispersed phase 1, and the chloroform solution of polylactic acid can be used as dispersed phase 2, and dispersed phase 1 can be cut into W / O microemulsion with dispersed phase 2, The continuous phase in which the hydrophilic emulsifier is dissolved is then sheared into the dispersed phase 2 again to form a W / O / W microemulsion.

[0043] (3) Preparation of ...

Embodiment 1

[0045] Embodiment 1, preparation polylactic acid microsphere

[0046] The microfluidic chip device as figure 1 As shown assembled. A chloroform solution of 30 mg / mL polylactic acid (molecular weight 10000) was prepared; a solution of PVA (model: average degree of polymerization 1750±50) with a mass concentration of 2% was prepared as the continuous phase. The dispersed phase and the continuous phase were transported to the microfluidic chip by a micropump (see figure 2 ), in the chip, through the shearing action of the continuous phase, the dispersed phase forms monodisperse droplets (see image 3 ); for the hydrophilicity characterization of chip channel modification, see Figure 4 .

[0047] The collected droplets are placed in a water bath at room temperature to remove the organic solvent, and the pelletized material is precipitated and solidified into microspheres; the solidified drug-loaded microspheres are filtered, washed with water, and vacuum-dried or freeze-drie...

Embodiment 2

[0048] Example 2, preparation of polylactic acid microspheres wrapped with paclitaxel

[0049] The microfluidic chip device as figure 1As shown assembled. Prepare a chloroform solution of 30 mg / mL polylactic acid (molecular weight 10000), weigh a certain amount of paclitaxel and dissolve it in the above solution, and prepare solutions containing paclitaxel 1 mg / mL and 2 mg / mL respectively as the dispersed phase; prepare a mass concentration of 2 % PVA solution as the continuous phase. The dispersed phase and the continuous phase are transported to the microfluidic chip by a micropump to form monodisperse droplets; the collected droplets are placed in a 40°C water bath to remove the organic solvent; the solidified drug-loaded microspheres are filtered and washed with water , vacuum-dried or freeze-dried at room temperature.

[0050] attached Figure 6 (a-b) are the optical micrographs of the prepared drug-loaded polylactic acid microspheres with different particle sizes, fl...

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Abstract

The invention discloses a method for preparing mono-disperse microemulsion, liposome and microspheres based on a microfluidic technology. The method comprises the following steps: taking aqueous solution (or oily solution) of a hydrophilic medicine (or a lipid-soluble medicine) as a disperse phase; taking an oil phase (or an aqueous phase) as a continuous phase; and respectively conveying the disperse phase and the continuous phase into corresponding micro-channels of a microfluidic chip device, shearing the phases into mono-disperse liquid drops of the encapsulated medicine, then curing the liquid drops by a certain curing method, and finally obtaining the medicine-carrying liposome, microspheres or the biodegradable microspheres with uniform size and dispersion stability. Under an optimum condition, the diameter distribution coefficients of the microemulsion and the microspheres can be less than 5%, and the diameter is 10-500microns. By utilizing the method, the problems such as uneven size, low embedding rate, poor dispersibility, poor targeting property, low bioavailability, low bioactivity of enzyme and cells, immune suppression and the like of the medicine-carrying microemulsion, the liposome and the microspheres prepared by the traditional ultrasonic method, agitation emulsification method and film hydration-dispersion method are solved.

Description

technical field [0001] The invention belongs to the field of pharmaceutical engineering drug preparations, and in particular relates to a method for preparing monodisperse microemulsions, liposomes and microspheres based on microfluidic technology. Background technique [0002] Microfluidic technology is an important science and technology, its main feature is integration and miniaturization, it will play a role in disease diagnosis, drug screening, environmental testing, food safety, judicial identification, sports competition, anti-terrorism, aerospace and other fields . Microfluidic chips are mainly characterized by the integration of microchannel networks and various functional units. They control and process micro-samples at the micro-scale, and realize the preparation, reaction, separation and detection of micro-samples. Droplets are a brand-new technology for manipulating tiny volumes of liquids developed on microfluidic chips in recent years. As a brand-new technol...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K9/127A61K9/16C12N11/00
Inventor 罗国安王义明梁琼麟何天稀
Owner TSINGHUA UNIV
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