Sodium alginate is a sodium salt of polyanionic alginic acid. It is a natural high molecular polysaccharide polymer extracted from natural brown algae. It has the advantages of wide source, low price, good biocompatibility, and degradability. Contains multiple hydroxyl and carboxyl functional groups, so it can react with a variety of divalent or trivalent cations to form hydrogels, and is widely used in biomedical fields such as cell engineering, drug sustained release, and medical dressings. When sodium alginate microspheres are applied to the fields of drug loading, controlled release, and interventional therapy, the control of particle size and morphology of the microspheres is particularly important. For large-sized microspheres ranging from hundreds of microns to millimeters, microspheres with a particle size of 130-1600 μm can be produced by using electrostatic spraying technology by controlling the relevant parameters of electrospraying. This method can achieve particle size control, but the productivity is low, and it is only suitable for Experimental research; spray-drying method can obtain microspheres with narrow particle size distribution and less than 2 μm, but the production of drug-loaded microspheres by this method has disadvantages such as high cost, limited by viscosity, thermal instability and low productivity, and it is difficult for production equipment There are certain requirements. Considering that the concentration of sodium alginate solution and the concentration of calcium chloride have an important influence on the gel properties of sodium alginate, sodium alginate microspheres can be prepared by emulsification and cross-linking method with simple operation, and then explore the microsphere morphology of different factors. The aim is to obtain microspheres with monodispersity, controllable particle size, narrow particle size distribution and good shape.
Preparation of Sodium Alginate Microspheres
Sodium alginate microspheres can be prepared by emulsification cross-linking method. Among them, the liquid paraffin containing Span 80 is used as the oil phase, and the sodium alginate solution is used as the water phase, and the oil-water volume ratio is 1:1. Stir at a certain speed to obtain a W/O (water-in-oil) type mixed emulsion. Add a certain concentration of calcium chloride solution dropwise to cause a cross-linking reaction. The reaction time is 2 hours. Finally, centrifuge at 4000 r/min for 10 minutes to separate the precipitate, and then wash and filter with petroleum ether, isopropanol and absolute ethanol. And then, dried in a vacuum oven at 50 °C for 3 h to obtain a light yellow powder. During the preparation process, the concentration of sodium alginate, the content of Span 80, the stirring speed and the concentration of calcium chloride were adjusted to explore their effects on the morphology and particle size of sodium alginate gel microspheres.
Analysis of Synthetic Factors of Sodium Alginate Microspheres
Infrared analysis
Infrared analysis of sodium alginate raw materials and sodium alginate microspheres shows that the vibrational absorption peak of the sodium alginate raw material at 2930 cm-1 is stronger than that of the prepared sodium alginate microspheres. An association reaction occurs between the molecular chains, which limits the vibration of the C-H bond and makes the dipole moment smaller; 1620 cm-1 is the characteristic absorption peak of -COOH, and the O-H absorption peak in carboxylic acid at 1421 cm-1. Studies found that the content of sodium alginate is key factors, and the peak intensity increases with the content of sodium alginate.
Microscopic Morphology Analysis
The study found that when the concentration of sodium alginate was low or high, there were more protrusions and broken microspheres on the surface, and the morphology of the microspheres was not good. The morphology of the microspheres obtained when the concentration of sodium phosphate was 3% was relatively best. As the concentration of sodium alginate increased, the particle size of the microspheres gradually increased. The reason is that the increase of sodium alginate concentration leads to the increase of the viscosity of sodium alginate solution, which increases the interfacial tension between the sodium alginate solution droplet and the oil phase, forming larger sodium alginate droplet, thus forming a more large microspheres.
The effect of Span 80 on microsphere preparation is: with the increase of Span 80 content, the dispersibility of microspheres was improved, and the morphology of microspheres was improved. This is because Span 80 plays a vital role as a surfactant in the process of preparing microspheres by emulsification cross-linking method, which can reduce the interfacial tension between hydrophilic and hydrophobic molecules and prevent emulsion droplets from being produced. When the discrete microspheres are coalesced, a stable emulsion is produced, which is conducive to the preparation of discrete microspheres. In addition, the surfactant also helps to modify and smooth the surface of the microspheres.
In addition, the analysis of the preparation of different stirring speeds found that the stirring speed has a certain influence on the morphology and dispersibility of the microspheres. Increasing the stirring speed will increase the shear force, and increasing the stirring speed can improve the microscopic morphology of the microspheres and reduce the phenomenon of microsphere agglomeration. Microscopic morphology analysis of microspheres prepared with different concentrations of crosslinking agent found that when the concentration of crosslinking agent was 3%, the concentration of Ca2+ was low, the crosslinking reaction was not complete, and the degree of hardening of microspheres was not high, so the morphology of microspheres was not good. Increase the concentration of the cross-linking agent, the concentration of Ca2+ increases, the reaction with the carboxylate of sodium alginate is more thorough, and the microspheres obtained have better morphology.
