Microfluidic preparation method for regulating and controlling particle size of lipidosome

A liposome and microfluidic chip technology is used in the preparation of liposome particle size regulation and the field of microfluidic control preparation for regulating liposome particle diameter, achieving good reproducibility, uniform particle size and expanding application prospects Effect

Active Publication Date: 2020-12-22
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, how to produce liposomes with different particle sizes by a variety of comprehensive factors has not been reported yet.

Method used

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  • Microfluidic preparation method for regulating and controlling particle size of lipidosome
  • Microfluidic preparation method for regulating and controlling particle size of lipidosome
  • Microfluidic preparation method for regulating and controlling particle size of lipidosome

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preparation example Construction

[0040] Preparation method of liposome

[0041] Liposome preparation method of the present invention, comprises the steps:

[0042] (1) the lipid material is dissolved in an organic solvent to form a lipid solution;

[0043] (2) preparation buffer;

[0044] (3) The lipid solution and the buffer solution are pumped into the microfluidic chip from different channel inlets for micro-mixing to obtain liposomes.

[0045] The lipid material is various natural or synthetic phospholipids, or a mixture of phospholipids and cholesterol.

[0046] The buffer is PBS, HEPES or TRIS.

[0047] The microfluidic chip is of SHM or Tesla structure.

[0048] SHM structure chip

[0049] The SHM structure chip refers to a chip with a staggered herringbone convex structure at the bottom after the confluence of multiple liquid flow channels. For a schematic diagram, see Figure 10 . The chevron-shaped convex structure can promote the fluid to generate helical streamlines with different rotation ...

Embodiment 1

[0057] This embodiment provides a microfluidic preparation method of liposomes, comprising the following steps:

[0058] (1) Preparation of ethanol solution (organic phase) of lipid materials: Weigh 8 mg of HSPC, 16 mg of cholesterol, and 32 mg of DOTAP, and dissolve them in 14 ml of ethanol.

[0059] (2) Prepare PBS buffer solution (water phase) (10mM, pH 7.4): weigh 0.2g KCl, 1.44g Na 2 HPO 4 , 0.24gKH 2 PO 4 , add 1L deionized water to dissolve, dilute to 10mM PBS with deionized water, adjust the pH to 7.4 with hydrochloric acid, pass through a 0.22μm filter membrane for later use.

[0060] (3) Prepare HEPES buffer (water phase) (10mM, pH 7.4): Weigh 2.3831g HEPES, add 100ml deionized water to dissolve, dilute to 10mM HEPES with deionized water, adjust pH to 7.4 with sodium hydroxide, pass The 0.22μm filter membrane is ready for use.

[0061] (4) Prepare Tris buffer solution (aqueous phase) (10mM, pH 7.4): weigh 121.1mg Tris, add 100ml deionized water to dissolve, adju...

Embodiment 2

[0066] This embodiment provides a microfluidic preparation method of liposomes, comprising the following steps:

[0067] (1) Preparation of ethanol solution (organic phase) of lipid material: weigh 24 mg of DMPC and 12 mg of cholesterol, and dissolve in 9 ml of ethanol.

[0068] (2) Prepare PBS buffer (water phase) (10mM, pH 6.8): weigh 8.0g NaCl, 0.2g KCl, 1.44gNa 2 HPO 4 , 0.24g KH 2 PO 4 , add 1L deionized water to dissolve, dilute to 10mM PBS with deionized water, adjust the pH to 6.8 with hydrochloric acid, pass through a 0.22μm filter membrane for later use.

[0069] (3) Prepare PBS buffer solution (water phase) (10mM, pH 7.4): weigh 8.0g NaCl, 0.2g KCl, 1.44gNa 2 HPO 4 , 0.24g KH 2 PO 4 , add 1L deionized water to dissolve, dilute to 10mM PBS with deionized water, pH is about 7.4, pass through a 0.22μm filter membrane for later use.

[0070] (4) Prepare PBS buffer (water phase) (10mM, pH 8.0): Weigh 8.0g NaCl, 0.2g KCl, 1.44gNa 2 HPO 4 , 0.24g KH 2 PO 4 , ad...

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Abstract

The invention discloses a microfluidic preparation method for regulating and controlling the particle size of lipidosome. The method comprises the following steps: A, dissolving a lipid material in anorganic solvent to form a lipid solution; and B, pumping the lipid solution and a buffer solution into a micro-fluidic chip from inlets of different channels respectively, and carrying out micro-mixing to obtain the liposome. According to a traditional liposome preparation method, under the condition that a lipid prescription is not changed, liposomes with different particle sizes and uniform distribution are difficult to prepare according to design requirements. The invention provides the micro-fluidic method, which prepares liposomes with different particle sizes by changing the compositionof a water phase buffer system, the composition of an organic phase and the proportion of the water phase to the organic phase on the premise of not changing the lipid prescription. The method is simple in process, the prepared liposome is adjustable in particle size, uniform in particle size and good in repeatability, and more possibilities are provided for biological application of the liposome.

Description

technical field [0001] The invention belongs to the research technical field of microfluidics and microreactor technology in pharmaceutical preparations, and specifically relates to a preparation method for regulating the particle size of liposomes, in particular to a microfluidic preparation method for regulating the particle size of liposomes. Background technique [0002] Liposome is a bilayer vesicle structure composed of lipid molecules. As a drug carrier, it can improve drug efficacy, increase drug solubility, prolong the residence time in vivo, and reduce drug toxicity, and has been widely used. At the same time, as a biofilm simulation, it also has a large number of applications in the field of biological research. In addition, liposome technology is also used in vaccines, cosmetics, lubrication and other fields. [0003] Liposome is used as a drug carrier, and its particle size is an important parameter. Liposomes of different sizes have significant differences in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01L3/00
CPCB01L3/502784B01L2200/06B01L2200/12
Inventor 陈剑贾玉洁张莉
Owner SHANGHAI JIAO TONG UNIV
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