A method for preparing micro-nano gel microspheres based on metastable emulsion

Abstract

The invention belongs to the field of bioengineering and relates to a method for preparing micro-nano gel microspheres based on a metastable emulsion. The method uses short-chain surfactants with one end being fluorophilic and the other end being hydrophilic to stabilize the fluorinated water-in-oil emulsion, which can obtain metastable emulsion droplets in a short time, less than 1 second, and then the droplets tend to merge , Emulsion breaking. The gel microspheres are obtained by solidifying the hydrogel prepolymer in the water phase within the droplet stability time window; after the spontaneous demulsification of the emulsion droplet system, the water and oil phases are automatically separated, and the gel microspheres Spontaneously dispersed in the aqueous phase. The method of the present invention can greatly simplify the emulsion droplet technology, including microfluidic droplet technology and traditional water-oil two-phase droplet technology, and the preparation process for preparing hydrogel microspheres, avoiding the need for cleaning after the traditional method prepares stable emulsion droplets It is of great significance for the large-scale scale-up production of gel microspheres to solve the difficult problem of demulsification and realize the one-step method of preparation and separation of gel microspheres.

Description

technical field [0001] The invention belongs to the field of bioengineering, and relates to a metastable emulsion system and a method for preparing micro-nano gel particles loaded with bioactive substances. Background technique [0002] Hydrogel materials have gradually become a very important biomaterial in the field of biomedicine. It is a cross-linked network composed of polymers that are insoluble in water but swellable in water. Similar to human tissue, it has abundant water-containing pores. structure. Such a porous structure is similar to human tissue and is very conducive to material exchange. At the same time, some hydrogel materials themselves are derived from biomacromolecules, have good biocompatibility, and have mild gelation conditions, so such materials are widely used for the encapsulation of living cells and bioactive substances. Although these hydrogels have been widely used in various bioengineering fields, there are still many problems to be solved in t...

AI Technical Summary

Problems solved by technology

Although these hydrogels have been widely used in various bioengineering fields, there are still many problems to be solved in their application forms based on traditional hydrogels: bulk hydrogels are large in size, and despite their porous structure, their The internal material transfer rate and transfer distance are still relatively low, resulting in a low survival rate of the internally encapsulated cells due to insufficient nutrients, or the internally encapsulated bioactive molecules cannot be released uniformly, effectively and completely

[0011] 1) The ionic surfactant itself has a certain water solubility. After a small amount of dissolution, it will directly affect the cell membrane or other active substances, resulting in cell death or inactivation of active substances, so it is not suitable for encapsulating cells or biologically active substances. use

[0012] 2) Nonionic surfactants have large molecules and poor water solubility, so they have relatively little effect on the activity of cells or biologically active substances; at the same time, their large molecular volumes lead to enhanced Gibbs-Marangoni effects, making it difficult to form droplets elution, resulting in difficult and cumbersome demulsification operations during product recovery; on the other hand, although its water solubility is poor, its lipophilic properties still allow it to react with some biologically active substances with similar molecular forms, thus limiting its use in Application in the encapsulation of corresponding substances

However, its production process is cumbersome and costly. At the same time, the stability of the emulsion is extremely strong, which increases the operation steps and cost of microgel preparation, and limits the possibility of forming a continuous production process. Therefore, there are certain limitations in practical application and continuous expansion of production. application restrictions

[0014] 4) The two-step method based on the existing surfactant to prepare the microgel is cumbersome, and the emulsification and cross-linking conditions are harsh, so it has a great impact on the activity of cells or encapsulated substances, and the multi-step production process is also difficult. Not suitable for expanded production and large-scale application

The existing methods to increase the curing time window have higher requirements on the droplet production device, and also face the problem of high basic cost in terms of process scale-up

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