Novel preparation method of solid lipid nanoparticles

A solid lipid nanotechnology, a new method, applied in the field of biomedicine, can solve problems such as aggregation, fusion, disintegration, and changes in drug encapsulation rate, and achieve the effect of simple production process, simple process, and controlled drug release rate

Inactive Publication Date: 2011-08-17
王汀 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] (5) Solvent emulsification method Dissolve the lipid material in an organic solution (such as cyclohexylamine, chloroform, dichloromethane, etc.), then add it to an aqueous phase containing an emulsifier for emulsification, and finally evaporate the organic solvent to obtain SLN Compared with the high-pressure emulsification method, the advantage of this method is that it can avoid the introduction of any thermal stress. The disadvantage is that it is difficult to completely remove the introduction of organic solvents. When large-scale production, polymer nanoparticles based on solvent volatilization technology will also be encountered. similar problems
When solid lipid nanoparticles (including NLC) are suspended in the water phase, aggregation and fusion often occur, resulting in a larger particle size, and in severe cases, aggregation and delamination may occur
[0013] (2) Phospholipids are usually prone to hydrolysis and oxidation when they exist in the water phase
Since phospholipids are hydrolyzed to form lysophospholipids, on the one hand, the toxicity of the preparation is increased, and on the other hand, it is easy to disintegrate the solid li

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] The effect of lyoprotectant sucrose on freeze-drying properties: 5% sucrose aqueous solution is used as water phase, 3% glyceryl stearate, 1% soybean lecithin (SPC) are dissolved in t-butyl alcohol (t-butyl alcohol, TBA ) is the oil phase, under the condition of rapid stirring (360rpm), inject 1ml of the oil phase into 5ml of the water phase in the form of a fine stream, and then divide it into 1ml / bottle, put it into a -80°C low-temperature refrigerator to freeze, and then transfer it to a lyophilizer. Dry, lyophilized product is hydrated with 1ml of water to obtain aqueous dispersion of solid lipid nanoparticles. It was found that the addition of sucrose as a lyoprotectant significantly improved the shape of the lyophilized product, accelerated the hydration rate, and the obtained lyophilized product could be stored for a long time.

Embodiment 2

[0047] The influence of lipid composition on the particle size of solid lipid nanoparticles: with 5% lactose aqueous solution as water phase, 1% SPC or 1% SPC / SPS (5: 1, w / w)+3%GMS are dissolved in ethanol as For the oil phase, under the condition of rapid stirring (600rpm), inject 3ml of the oil phase into 5ml of the water phase in the form of a fine stream, divide it into 1ml / bottle, put it into a liquid nitrogen filled with liquid nitrogen and freeze it, then transfer it to a lyophilizer for lyophilization , the lyophilized product was hydrated with 1ml of water to obtain an aqueous dispersion of solid lipid nanoparticles. The particle size was measured with LS230 (Beckmann company). The average particle diameters of the solid lipid nanoparticles are 136nm and 110nm respectively. This means that lipid components have a certain influence on the particle size of solid lipid nanoparticles, and charged components can reduce particle size and distribution.

Embodiment 3

[0049] Measure the average particle diameter of solid lipid nanoparticles with LS230 (Beckmann company) all less than 200nm, observe the solid lipid nanoparticles obtained in embodiment 1 and 2 with a scanning electron microscope, be nanospheres, and the size is the same as that measured with a particle size analyzer The results match.

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Abstract

The invention discloses a novel preparation method of solid lipid nanoparticles (SLN) (including nanostructured lipid carriers NLC), solving the unstable problem of easiness in aggregation, agglomeration, and the like of the solid lipid nanoparticles (including NLC). The preparation method comprises the steps of: a, dissolving lipid matters and lipotrophic matters (including medicines) in an organic solvent (such as tertiary butanol) capable of being mixed and dissolved with water to form an oil phase (O), or solubilizing hydrophilic matters (including medicines) in an organic solvent (O) capable of being mixed and dissolved with water by using a surfactant, wherein the lipid matters and the lipotrophic matters are used for forming the solid lipid nanoparticles (including NLC); b, dissolving water-soluble matters in water to form a water phase (W); c, injecting the oil phase (O) into the water phase (W) under stirring condition according to a proper volume proportion to obtain a solid nanoparticle dispersing solution; d, freezing and drying the obtained dispersing solution to remove the solvent to obtain a freeze-dried product; and e, hydrating the obtained freeze-dried product to obtain the solid lipid nanoparticles (including NLC). The preparation method is simple in procedures and easy to implement.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a new method for preparing solid lipid nanoparticle (including NLC) drug carriers. Background technique [0002] Solid lipid nanoparticles (including NLC) are nanoparticles formed by layers of lipid molecules. Solid lipid nanoparticles (including NLC) can be divided into two types according to their structure: solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The former is prepared from solid lipid materials at room temperature, and the latter is obtained by adding part of liquid lipid components during the preparation of the former. Solid lipid nanoparticles have been developed as drug carriers since 1990, and soon entered the market as cosmetics. As material carriers, especially drug carriers, solid lipid nanoparticles (including NLC) have great application value. At present, people are conducting systematic and extensive research on solid lipid nan...

Claims

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Application Information

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IPC IPC(8): A61K9/19
Inventor 王汀周亚球王宁
Owner 王汀
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