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Emulsification-solvent evaporation method: This is the most commonly used method for preparing microspheres. The drug and polymer are dissolved in two immiscible solvents respectively, and then an emulsion is made by emulsification. Then the internal dispersed phase solvent is evaporated, and the spherical material is precipitated and solidified into microspheres
Phase separation method: A third component is added to the organic solution of the polymer to reduce the solubility of the polymer, resulting in two liquid phases (phase separation), thereby preparing microspheres
Spray drying method: After the drug and carrier polymer are dissolved in an organic solvent, they are sprayed into an inert gas flow through a sprayer to form small droplets, and then the solvent is rapidly evaporated by controlling the temperature, and the droplets shrink into microspheres
Hot melt extrusion method: The polymer is melted by heating, and then solidified into microspheres by extrusion and cooling.
Membrane emulsification, microfluidics and supercritical fluid technology: These emerging technologies have gradually become research hotspots due to their advantages such as uniform particle size, controllable distribution and environmental friendliness.
Local treatment of malignant tumors: Microspheres encapsulated with anti-tumor drugs can reduce adverse reactions through local or in situ administration strategies, such as porous polylactic acid microspheres prepared by double emulsion method and solvent extraction method, using the self-healing properties of PLA to achieve sustained release effect
Treatment of orthopedic diseases: Microspheres can provide a stable microenvironment, retain cytokine activity for a long time and achieve sustained release effect, such as PLGA microspheres loaded with manganese dioxide nanoparticles and bone morphogenetic protein-2
Treatment of central nervous system diseases: For example, microspheres can improve the survival rate and differentiation efficiency of neural stem cell transplantation in spinal cord injury
Treatment of respiratory diseases: Microsphere drug delivery system can improve drug stability and long-term sustained release of drugs The role of drugs, such as microsphere inhalation aerosols for COVID-19
Regulating intestinal flora: Microspheres can encapsulate probiotics and treat gastrointestinal diseases by regulating intestinal flora
Control of drug release rate: The drug release rate of microsphere drug delivery systems is affected by many factors, such as carrier materials, drug properties and preparation processes, and is difficult to accurately control
Inconsistency between in vitro drug release and in vivo blood drug concentration curves: Long-term microsphere preparations often lead to inconsistencies between in vitro drug release curves and in vivo blood drug concentration curves, which require repeated and long-term animal experimental verification
Lack of standardized equipment: Currently, the equipment for preparing drug-loaded microspheres is generally independently developed or improved equipment, and there is a lack of standardized equipment
Preparation of drug-loaded microspheres:
Electrospinning technology can be used to prepare nanofibers coated with drug-loaded microspheres. For example, silk fibroin microspheres can be prepared by self-assembly, and hydrophobic drugs can be loaded into them. These drug-loaded microspheres are then sealed into electrospun nanofibers with the help of electrospinning technology to form a silk fibroin microsphere/electrospun nanofiber composite carrier
Drug release control:
Electrospinning technology can prepare nanofibers with specific drug release characteristics. By adjusting the parameters in the electrospinning process, such as voltage, flow rate, distance, etc., the fiber morphology and drug release behavior can be controlled to achieve controlled drug release
Clinical application challenges:
The challenges faced by electrospinning technology in the clinical transformation of microsphere preparations include precise control of drug release rate and lack of standardized equipment. Through interdisciplinary cooperation, we can jointly solve the problems in the process of drug-loaded microsphere process scale-up and continuously optimize the drug-loaded microsphere preparation process
