Development Of Multifunctional Drug-loaded Polymeric Yolk-Shell Particles Via Electrohydrodynamic Technique For Biomedical Applications

Yolk-shell microparticles have been widely concerned in a lot of biomedical applications,including biosensing,drug delivery,and theranostics,because of their outstanding advantages,including low density,large specific surface area,and excellent loading capacity.However,polymeric yolk-shell microparticles were barely mentioned in publications.Electrohydrodynamic technique is a material processing method which is widely used for the fabrication of polymeric materials in the micro/nano scale.With this method,polymeric microparticles or ultrafine fibers can be fabricated in one step.Hence,drug-loaded polymeric yolk-shell particles are expected to be fabricated by this technique.In this study,fabrication of drug-loaded polymeric yolk-shell particles and their applications in the biomedical fields are investigated based on the triaxial electrospraying technique utilizing the electrohydrodynamic devices.The main contents and contributions of this thesis are given as follows:1.Development of polymeric composite microparticles via triaxial electrospraying and investigation of influence factorsCompared with the traditional single needle electrospraying technique,triaxial electrospraying utilized three polymer solutions,the physicochemical properties of each polymer solution,the interactions between different solutions,and the processing parameters are all likely to influence the stability of the triaxial electrospraying process and the morphology and structures of the final products.Up to now,there is no relevant literature which has studied these influence factors in detail in triaxial electrospraying process.In this study,the major influence factors of triaxial electrospraying were investigated employing PCL as the material for the inner and outer layer,meanwhile using silicone oil and other polymers as the middle layer material.The results indicated that,factors including the type of polymers,polymer molecular weights,solution concentration,flow rate,applied voltage,and collecting distance all have the potential to influence the stability of the triaxial electrospraying process as well as the morphology and structure of the yielded products.Thus,the stable jetting mode and the targeted products are expected to be obtained by adjusting the aforementioned factors.2.Development of multifunctional drug-loaded polymeric yolk-shell particles via triaxial electrospraying technique and assessment of their functionsParticulate platforms capable of delivering multiple actives as well as providing diagnostic features are playing more and more important role in biomedical fields.In this study,magnetic polymer yolk-shell particles(YSPs)were produced utilizing triaxial electrospraying technique enabling dual-mode(ultrasonic and magnetic resonance)imaging capability with specific multidrug compartments via an advanced single-step encapsulation process.The fabricated magnetic polymer yolk-shell particles consisted of magnetic Fe3O4 nanoparticles embedded in the polymeric shell,an interfacing oil layer,and a polymeric core.Three fluorescent dyes were encapsulated separately into different layers to simulate the release process of drugs with different hydrophobicity.The results indicated that the frequency of the ultrasound backscatter signal was modulated through YSP loading dosage,and the contrasts of both T1-and T2-weighted magnetic resonance images were enhanced with increasing MNP content in the outer layer of the YSPs.Probe release profiles were tuned by varying power or frequency of an external auxiliary magnetic field.The biocompatibility of the fabricated YSPs was confirmed by culturing with mouse L929 cells.In summary,magnetic YSPs demonstrate timely potential as multifunctional theranostic agents for dual-imaging modality and magnetically controlled coactive delivery.3.Development of multifunctional drug-loaded polymeric porous yolk-shell particles via triaxial electrospraying technique combined with non-solvent method and assessment of their functionsUtilization of non-solvents of the polymers can effectively regulate the surface morphology and internal structure of the electrosprayed products,and help realize the development of micro/nano materials with relatively complex morphology and structure.In this study,drug-loaded porous polymeric yolk-shell particles(YSPs)were fabricated by the combination of triaxial electrospraying technique and non-solvent method.The matrix materials of the shell and core of the fabricated YSPs were PCL,and TiO2-Ag nanoparticles and Ganoderma lucidum polysaccharides were encapsulated into the outer shell of the YSPs as the major antibacterial and antioxidant components,meanwhile iron oxide nanoparticles were incorporated into the inner core to act as photothermal agent.The morphology and structure,chemical composition,biocompatibility,antioxidant effect,antibacterial effect,and photothermal effect of the fabricated YSPs,as well as the release profile of the encapsulated GLP were studied in vitro.Furthermore,in vivo wound healing effects of the YSPs and the laser-assisted therapy were explored based on a burn wound model on c57 mice.4.Development of porous scaffolds with hierarchical pore structures via triaxial electrospraying combined with template removal methodCell scaffolds with hierarchical pore structures are playing increasingly important roles in tissue engineering,and the fabrication and control of their pore structures are of great significance to the realization of their functions.In this work,cell scaffolds with hierarchical pores structures were fabricated using triaxial electrospraying technique combined with template removal method.Firstly,solid tri-layer particles were fabricated using triaxial electrospraying and solid composite films were produced by deposition of the fabricated particles;then the porogen in the shell of the particles(Ethyl Cellulose)and the middle layer(Silicone Oil)were removed by corresponding solvents,after which hierarchically porous cell scaffolds(consists of porous yolk-shell particles)were obtained.The shell of each constituent porous particle consisted of a porous PCL shell loaded with GLP and a solid core loaded with Fe3O4 nanoparticles.It is proved that the fabricated scaffolds had hierarchical pores with relatively high porosity,fast drug release characteristic,and good biocompatibility.The seeded L929 cells could attach and proliferate on the surface and into the center region of the fabricated porous scaffolds.Furthermore,the incorporated Fe3O4 nanoparticles endowed the scaffolds with superparamagnetic properties,and made the scaffolds traceable by MRI T1-and T2-weighted imaging,which could make it possible to realize non-invasive detection of its position and macroscopic structure.This work has carried out extensive research on the construction and biomedical application of the multifunctional drug-loaded Yolk-shell particles based on triaxial electrospraying technique,which may provide reference value for the development of both polymeric micro/nano materials and multifunctional drug carriers.