Scale Up of PLA Nanoparticle Synthesis by Solvent Displacement and Functionalization of the Particles with a Silica Shell for Targeted Drug Delivery Applications

Biodegradable polymer nanoparticles have the properties necessary to address many of the issues associated with current drug delivery techniques including targeted and controlled delivery. A novel drug delivery vehicle is proposed consisting of a poly(lactic acid) nanoparticle core, with a functionalized, mesoporous silica shell. In this study, the production of PLA nanoparticles is investigated using solvent displacement in both a batch and continuous manner, and the effects of various system parameters are examined. Using Pluronic F-127 as the stabilization agent throughout the study, PLA nanoparticles are produced through solvent displacement with diameters ranging from 200 to 250 nm using two different methods: dropwise addition and in an impinging jet mixer. The impinging jet mixer allows for easy scale-up of particle production. The concentration of surfactant and volume of quench solution is found to have minimal impact on particle diameter; however, the concentration of PLA is found to significantly impact the diameter mean and polydispersity. In addition, the stability of the PLA nanoparticles is observed to increase as residual THF is evaporated. Lastly, the isolated PLA nanoparticles are coated with a silica shell using the Stöber Process. It is found that functionalizing the silica with a phosphonic silane in the presence of excess Pluronic F-127 decreases coalescence of the particles during the coating process. Future work should be conducted to fine-tune the PLA nanoparticle synthesis process by understanding the effect of other system parameters and in synthesizing mesoporous silica shells.

Effects Of The Flash Welding Process On Mechanical And Microstructural Properties Of Structural Steel Joints Assessed Using Dest

ASTM A529 carbon¿manganese steel angle specimens were joined by flash butt welding and the effects of varying process parameter settings on the resulting welds were investigated. The weld metal and heat affected zones were examined and tested using tensile testing, ultrasonic scanning, Rockwell hardness testing, optical microscopy, and scanning electron microscopy with energy dispersive spectroscopy in order to quantify the effect of process variables on weld quality. Statistical analysis of experimental tensile and ultrasonic scanning data highlighted the sensitivity of weld strength and the presence of weld zone inclusions and interfacial defects to the process factors of upset current, flashing time duration, and upset dimension. Subsequent microstructural analysis revealed various phases within the weld and heat affected zone, including acicular ferrite, Widmanstätten or side-plate ferrite, and grain boundary ferrite. Inspection of the fracture surfaces of multiple tensile specimens, with scanning electron microscopy, displayed evidence of brittle cleavage fracture within the weld zone for certain factor combinations. Test results also indicated that hardness was increased in the weld zone for all specimens, which can be attributed to the extensive deformation of the upset operation. The significance of weld process factor levels on microstructure, fracture characteristics, and weld zone strength was analyzed. The relationships between significant flash welding process variables and weld quality metrics as applied to ASTM A529-Grade 50 steel angle were formalized in empirical process models.