Investigation On Fabrication Of Drug Microcarriers By Flow Focusing Method

The traditional drug carriers preparation methods have some disadvantages,such as low encapsulation rate,poor particle dispersion and uncontrollable inclusion composition.As one of the important parts of microfluidic technology,flow focusing(FF)technology has many advantages,such as easy operation,good stability,high encapsulation rate,wide applicability and does not require rigorous conditions.In this paper,perfluorocarbon(PFC)?indocyanine Green(ICG)or magnetic Nanoparticles(MNPs)encapsulated multifunctional microcarriers are produced by flow focusing method.The applications of the produced multifunctional carriers in ultrasound imaging,controlled excitation,fluorescence imaging,drug delivery,magnetic separation and in vitro targeting were also studied.The specific contents are as follows:].A droplet-based microfluidic flow-focusing system was developed for on-chip fabrication of stimuli-responsive microdroplets(SRMs)that underwent rapid liquid-to-gas phase transition and volume expansion upon external stimuli.Silver nanoparticles(SNPs)were suspended in perfluorocarbon(PFC)liquid and encapsulated in a lipid shell to form a SRM.The SRM size can be well controlled from 4?m to 50?m by adjusting the flow rates of the inner and the outer liquid phases.The acoustic and the optical droplet vaporizations of the SRMs were demonstrated in benchtop experiments.Upon acoustic stimulation by a therapeutic ultrasound transducer at 1 MHz and 1 W/cm2,the SRMs were activated and the induced echogenicity was monitored by clinical ultrasonography.Upon optical stimulation by a 445 nm laser beam at a power intensity of larger than 35 W/cm2,the SRMs were activated and the volume expansion of the SRMs was monitored by bright field microscopy.Our benchtop experiments demonstrated the technical feasibility for acoustic and optical mediation of the SRMs.The technique can be potentially used for multiple therapeutic applications such as thermal ablation,vascular occlusion,and locoregional drug delivery.2.A facile liquid-driven coaxial flow focusing(LDCFF)was proposed to encapsulate high concentration Indocyanine Green(ICG)in monodisperse bilayer liposomes for potential application in quantitative fluorescence imaging and image-guided drug delivery.The microencapsulation process follows two consecutive steps of droplet formation by LDCFF and solvent removal by oil phase dewetting.The influence of fluid flow rates on the size of the produced droplets is studied for the improved process control.The utility of the ICG liposomes is tested in the simulated drug release experiments where ethanol is added in the PVA or plasma suspension of ICG liposomes to dissolve the liposomal membrane and release ICG.Fluorescence emission is enhanced significantly after the liposomal membrane is dissolved and the increase of fluorescence emission is linearly correlated with the concentration of ICG liposomes.Considering that ICG is an FDA(The US Food and Drug Administration)approved fluorescence agent,the produced ICG liposomes can be used as a biocompatible sensor for quantitative clinical imaging and image-guided drug delivery.The proposed LDCFF process can be extended to encapsulate hydrophilic and hydrophobic drugs,DNA,proteins,and other therapies at high concentration by using various shell materials.3.A facile liquid-driven compound-fluidic flow focusing(LCFF)process was proposed to produce uni-and multi-compartmental poly(lactic-co-glycolic acid)(PLGA)microcapsules in high production rates.The experimental setup mainly consists of a stainless steel needle assembly mounted in a chamber with its end facing a small orifice at the bottom of the chamber.Magnetic nanoparticles(MNPs)encapsulated uni-compartmental microcapsules were produced and the magnetic-controlled aggregation and separation were demonstrated in benchtop experiments.Such microcapsules can be site-and/or route-specifically delivered to a desired site with the help of an external magnetic field.Also,interactive materials encapsulated multi-compartmental microdroplets were produced and the controlled microreaction was investigated.The size and morphology of the PLGA microcapsules can be controlled by adjusting the multiphase fluid flow rates.The proposed LCFF process can be potentially used to produce different kinds of multifunctional microcarriers for multiple applications.