The preparation method of microspheres is the key to choose the route of administration and control the drug release. At present, the preparation methods of sodium alginate microspheres mainly include emulsion ionic crosslinking method, microemulsion method, complex coagulation method, orifice plate coagulation bath method, electrostatic drop method and improved preparation methods of the above methods.
1.？ Emulsified ionic crosslinking method? This method refers to mixing the drug with sodium alginate solution evenly, then dropping it into a certain oil phase and stirring to make W/O emulsion, then adding ion crosslinking agent for crosslinking and curing, and stirring and separating to obtain drug-loaded microspheres [4]. Liu Shankui et al. [5] prepared DNA vaccine sodium alginate microspheres by this method, and Li Guoming et al. [6] continued to react with chitosan solution to prepare amitriptyline hydrochloride sodium alginate-chitosan microspheres after crosslinking and curing. Ramesh et al. [7] improved this method and prepared Li Xinping sodium alginate-methylcellulose (MC)*** mixed microspheres. The results show that with the increase of MC content in microspheres, the water absorption of microspheres decreases, and the MC content is related to the drug release rate of microspheres The density of the microspheres is low, which can be maintained for more than 65438±02h in the stomach environment, thus effectively improving the Li Xinping.
2.？ Microemulsion method? In this legal system, a certain amount of sodium alginate and drugs are dissolved in distilled water and mixed with each other, and a certain amount of mixed solution is added to the oil phase drop by drop under the conditions of ultrasound and high-speed stirring to form a microemulsion system. Then the CaCl2 _ 2 solution is added into the mixed solution drop by drop, and the mixture is continuously stirred, washed, freeze-dried and stored to obtain the sodium alginate drug-loaded microspheres. This method is mostly used in the preparation of magnetic microspheres to obtain drug-loaded magnetic microspheres with small particle size, uniformity and strong targeting. Yan [8] prepared adriamycin magnetic nanoparticles with strong magnetic response and sustained release by this method. It is found that the microspheres have small particle size, good dispersibility and magnetic targeting function, and are expected to become excellent drug carriers for targeting tumors. Su Ke et al. [9] further improved this method. On the basis of the obtained adriamycin magnetic microspheres, water-soluble diimine and monoclonal antibody human transferrin were added, and the human transferrin modified sodium alginate drug-loaded adriamycin nanoparticles (TDA) were obtained after rotary mixing, separation and freeze-drying. In addition, Chuah et al [10] improved on this basis, and sodium alginate microspheres with uniform size were prepared by methyl cellulose emulsification combined with external gel method. ?
3.？ Compound coagulation? As sodium alginate is an anionic polymer, composite microspheres can be prepared by composite coagulation with cationic polymers. At present, chitosan and alginate are commonly used to form spheres, and polylysine is also commonly used to prepare composite microspheres. The microspheres obtained in this way have strong membrane wall strength and are suitable for practical application. In this system, sodium alginate solid is dissolved and dispersed evenly in distilled water, and surfactant is added and stirred continuously to form W/O emulsion. Dissolve chitosan with acetic acid, then add CaCl2 _ 2 _ 2 and medicine into a separatory funnel, and add them into W/O emulsion drop by drop with stirring. Adding glutaraldehyde for curing, adding n-butanol, fully oscillating, standing and centrifuging to obtain a precipitate, namely chitosan-sodium alginate drug-loaded microspheres. Li Zhulai et al. [1 1] used chitosan-sodium alginate as matrix material to prepare ceftriaxone microspheres in emulsion system by complex coacervation method. The microspheres had good swelling and sustained release properties. Wang Jin et al [12] prepared ibuprofen chitosan-sodium alginate sustained-release microspheres by complex coacervation method with good sphericity, uniform roundness, small particle size, high encapsulation efficiency, good stability and obvious sustained-release effect.
4.？ Sharp hole coagulation bath? In this legal system, drugs are added into sodium alginate solution, stirred evenly, the mixture is dropped into CaCl2 solution by syringe or microporous silicone tube, stirred and solidified, the separated microspheres are moved into chitosan solution, stirred and crosslinked continuously, and the separated microspheres are washed with distilled water and dried to obtain drug-loaded microspheres. Gao Chunfeng et al [13] used this method to prepare chitosan-sodium alginate sustained-release microspheres of tripterygium wilfordii polyglycoside extract. The results show that the concentration of sodium alginate, chitosan, calcium chloride and the mass ratio of sodium alginate to drug all affect the embedding rate, drug loading and in vitro release, while the crosslinking curing time affects the embedding rate and drug loading, but has no obvious effect on in vitro release. Huang Lan et al. [14] formed a complex of cationic-β-cyclodextrin polymer (CP-β-CD) and insulin, prepared a sodium alginate/chitosan microsphere system containing this complex, and applied it to oral insulin system. The results show that the addition of CP-β-CD can effectively improve the encapsulation efficiency and release of insulin in simulated intestinal juice, and it is a promising adjuvant for oral insulin preparation.
5.？ Electrostatic drop method? In this method, the capsule material and the liquid medicine are stirred and mixed, and the sodium alginate solution is added under the stirring condition. Under the action of the driving force of the syringe and the electric field force, the raw material solution is dropped into the low-temperature CaCl2 _ 2 solution.
Quickly curing to form calcium alginate gel microspheres, soaking, cleaning and vacuum drying at room temperature. Gu Jiwei et al. [15] prepared oxaprozin chitosan-sodium alginate sustained-release microspheres with particle size less than 1 mm by this method.
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