Novel preparation method of solid lipid nanoparticles

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...

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 lipid nanoparticles (including NLC), resulting in the leakage of the encapsulated drug.

[0014] (3) Solid lipid nanoparticles (including NLC) are suspended in the aqueous phase, during storage, the drug may leak, resulting in a change in the drug encapsulation rate, thereby affecting the efficacy of the preparation

If the drug itself is easily hydrolyzed, the stability problem of the formulation is more prominent

[0015] 2. The problem of encapsulation efficiency. The solid lipid nanoparticles (including NLC) preparations obtained by existing methods often have low encapsulation efficiency of water-soluble drugs.

Low encapsulation efficiency will not only cause waste of raw materials, but also may not reach the effective dose, which cannot reflect the advantages of solid lipid nanoparticles (including NLC) preparations

[0016] 3. Sterilization of solid lipid nanoparticles (including NLC) preparations Due to the nature of phospholipids, it is generally not possible to heat-sterilize the final preparation, which requires that the entire production process must be aseptic

This in turn often leads to further leakage of the drug, affecting the quality of the formulation