生物活性物质递送体系下丝素蛋白微胶囊的研究进展

Research development of silk protein microcapsules in bioactive compound delivery system

药物、香味剂、营养成分等生物活性物质易受到外界环境影响,导致其活性迅速降低。在使用过程中,如何长久稳定其活性是当前亟须解决的问题。丝素蛋白具有出色的生物相容性、安全性及优异的可塑性,基于丝素蛋白材料对生物活性物质具有高度的亲和性和持久的稳定性。近年来,热点之一的丝素蛋白微胶囊在生物活性物质的装载、稳定和递送等方面已被深入研究。本文从递送体系角度出发,分别从丝素蛋白微胶囊的材料选择、成囊机理、制备方法和理化性能的影响因素及应用现状5个方面进行了综述,并重点比较了丝素蛋白微胶囊的制备方法及理化性能的影响因素。综合分析表明,丝素蛋白微胶囊的研究应着重围绕制备方法的开发、理化性能的提升、生物活性物质长久高效的稳定及特定递送体系下的功能化和智能化等方面入手,为应用于疾病治疗、食品保护、生物传感器等领域提供材料选择。

Biologically active compounds such as drugs,flavors and nutrients can maintain normal physiological functions and prevent diseases during human life activities,but are easily degraded and inactivated under external stimuli such as light,temperature,pH and ionic strength.The development of new technologies to keep the biologically active compounds lasting and improve the utilization value is the focus of researchers.Among them,one of the most promising encapsulation delivery technologies is to entrap biologically active compounds in carrier matrices,which can effectively protect the activity from being destroyed,control the release rate and improve the utilization efficiency in vivo.Compared with other delivery carrier materials,silk protein has outstanding advantages.Firstly,silk protein has excellent biocompatibility,low immunogenicity,controllable degradability and high safety;secondly,the preparation conditions are mild,and microcapsules can be directly formed in aqueous solution without adding crosslinking agent,and the biological activity can be preserved to the greatest extent;finally,its applicability can be expanded by flexibly regulating the hydrophobicity,β-sheet content,solution conformation behavior,material morphology and chemical modification of silk protein molecules.Silk protein microcapsules have made a breakthrough in the stabilization and delivery system of biologically active substances.This article firstly elaborated that silk fibroin encapsulation mechanism includes four stages,namely,phase separation,adsorption on the surface of the wall material,refolding and self-assembly,and gradual thickening of aggregation.Silk silk fibroin concentration,core material template size and external stimuli will influence the encapsulation process.Secondly,it listed and compared the microcapsule preparation methods,including spray drying,complex coacervation,layer-by-layer assembly(LBL),and emulsion template self-assembly.Among them,the emulsion template self-assembly method is simple,mild and efficient,no organic solvents and cross-linking agents are added,and no strong acid is needed to erode the template.In this way,the biological safety of silk protein microcapsules can be guaranteed.Therefore,it is most expected to be industrialized.Then,it reviewed the physical and chemical properties of silk fibroin microcapsules,including the particle size,wall thickness and roughness,mechanical strength,permeability,etc.,and their effects on the stability and functioning of biologically active compounds were analyzed.Finally,it described the loading of silk protein microcapsules in plasmid DNA(pDNA),RNA and other active compounds and the research progress in delivery systems.Meanwhile,it compared the differences in cellular uptake,biocompatibility,and bio-distribution of microcapsules with different shapes.The biconcave microcapsules are not easy to be metabolized by the kidneys and liver,and can exhibit long blood circulation time,accumulate in the lungs and provide a useful reference for loading active drugs to treat lung diseases(pulmonary fibrosis,asthma and lung cancer).Although silk protein microcapsules have potential advantages in delivery carriers,food protection agents,and biosensors.However,researchers should focus on in-depth research on the loading and stabilization of biologically active macromolecules,as well as functionalization and intelligent design under the requirements of delivery systems.