In this work, the microencapsulation of water-soluble drug (doxorubicin, Dox) and imaging agent (perfluorocarbon, PFC) is performed by a novel liquid driven tri-axial flow focusing (LDTFF) device. The formation of stable triple-layered cone-jet mode can be observed in the simple well-assembled LDTFF device, providing an easy approach to fabricate mono-disperse triple-layered microcapsules with high encapsulation efficiency, high throughput and low cost in just one step. The fluorescence images show that the microcapsules have a satisfactory core-shell structure. The SEM micrographs show spherical and smooth surface views of the triple-layered microcapsules after being stirred 72h to remove the organic solvent totally. The results of thermo-responsive release experiments of the produced triple-layered microcapsules show these multifunctional capsules can be well stimulated when the environment temperature is beyond 55 degree centigrade. In a word, this novel approach has a great potential in applications such as drug delivery and image-guided therapy.
Curcumin-loaded PLGA microcapsules are fabricated by a liquid-driving coaxial flow focusing device. In the process, a stable coaxial cone-jet configuration is formed under the action of a coflowing liquid stream and the coaxial liquid jet eventually breaks up into microcapsules because of flow instability. This process can be well controlled by adjusting the flow rates of three phases including the driving PVA water solution, the outer PLGA ethyl acetate solution and the inner curcumin propylene glycol solution. Confocal and SEM imaging methods clearly indicate the core-shell structure of the resultant microcapsules. The encapsulation rate of curcumin in PLGA is measured to be more than 70%, which is much higher than the tranditional methods such as emulsion. The size distribution of resultant microcapsules under different conditions is presented and compared. An in vitro release simulation platform is further developed to verify the feasibility and reliability of the method.
Microencapsulation of drugs and imaging agents in the same carrier is of great significance for simultaneous detection and treatment of diseases. In this work, we have developed a tri-axial electro-flow focusing (TEFF) device using three needles with a novel concentric arrangement to one-step form multilayered microparticles. The TEFF process can be characterized as a multi-fluidic compound cone-jet configuration in the core of a high-speed coflowing gas stream under an axial electric field. The tri-axial liquid jet eventually breaks up into multilayered droplets. To validate the method, the effect of main process parameters on characteristics of the cone and the jet has been studied experimentally. The applied electric field can dramatically promote the stability of the compound cone and enhance the atomization of compound liquid jets. Microparticles with both three-layer, double-layer and single-layer structures have been obtained. The results show that the TEFF technique has great benefits in fabricating multilayered microparticles at smaller scales. This method will be able to one-step encapsulate multiple therapeutic and imaging agents for biomedical applications such as multi-modal imaging, drug delivery and biomedicine.
Microencapsulation of multiple drugs and imaging agents is significant for various biomedical applications. In this work we describe a novel method based on flow focusing geometry using tri-axial metallic capillary needles manufactured by a laser beam welding process. The tri-axial needle can be readily cleaned, assembled, and aligned. With this needle assembly, we develop a tri-axial capillary flow focusing device in which different combinations of liquids are focused in the core of a high-speed gas stream coflowing through a small orifice. Under appropriate working conditions, stable cone-jet configurations with three layers of liquids in an external gas stream can be obtained, resulting in multilayered microparticles with outer shell, middle layer, and inner core. The new design of tri-axial needles enables reliable encapsulation of multiple drugs and imaging agents in biodegradable microcapsules with the enhanced size distribution, increased productivity, and improved drug-loading efficiency. Furthermore, in this method the outer and the middle shell fluids can be released to produce monodisperse microparticles at smaller scales which have potential applications in multi-modal imaging, drug delivery, material processing and biomedicine.
Encapsulation of curcumin in PLGA microparticles is performed by a coaxial electrohydrodynamic atomization device. To optimize the process, the effects of different control parameters on morphology and size distribution of resultant microparticles are studied systemically. Four main flow modes are identified as the applied electric field intensity increases. The stable cone-jet configuration is found to be available for fabricating monodisperse microparticles with core-shell structures. The results are compared with those observed in traditional emulsion. The drug-loading efficiency is also checked. The present system is advantageous for the enhancement of particle size distribution and drug-loading efficiency in various applications such as drug delivery, biomedicine and image-guided therapy.
Microcapsules with multiple components inside a biodegradable shell are of great significance in various applications
such as biomedicine, biochemistry, sustained drug delivery and image-guided therapy. Here we report a compoundfluidic
electro-flow focusing (CFEFF) process that has the potential to one-step envelope multiple drugs and imaging
agents separately into a single microcapsule. In this method, a compound needle is assembled by embedding two parallel
thin inner needles into a relatively large outer needle. Two kinds of core fluids flow through the inner needles separately
and the shell fluid flows through the outer needle. Under the action of aerodynamic and electric driving forces, stable
cone-jet configurations can be obtained, resulting in multilayered microcapsules after the breakup of the compound
liquid jet because of flow instability. The feasibility and effectiveness of using this CFEFF method to encapsulate
multiple components into one shell is verified experimentally. The effects of various process parameters on the
morphology and size of the microcapsules are further studied.
Silver nanoparticles and perfluorocarbon are encapsulated in multilayered lipid microbubbles by a coaxial electro-flow
focusing process. The process is characterized as a coaxial liquid jet in the core of a high-speed coflowing gas stream
under an axial electric field. Different flow modes are identified and the stable cone-jet structure is formed in a wide
range of process parameters. Core-shell structures of microbubbles with nanoparticles inside the shell are clearly
observed. The effects of the main process parameters on the process outcome are studied systemically for the enhanced
microbubble morphology. The preliminary elevation of the temperature in silver nanoparticle suspended perfluorcarbon
is observed upon exposure to broadband light illumination, indicating the technical potential for light-activated drug
delivery.
Recent developments in multimodal imaging and image-guided therapy requires multilayered microparticles that encapsulate several imaging and therapeutic agents in the same carrier. However, commonly used microencapsulation processes have multiple limitations such as low encapsulation efficiency and loss of bioactivity for the encapsulated biological cargos. To overcome these limitations, we have carried out both experimental and theoretical studies on coaxial electrospray of multilayered microparticles. On the experimental side, an improved coaxial electrospray setup has been developed. A customized coaxial needle assembly combined with two ring electrodes has been used to enhance the stability of the cone and widen the process parameter range of the stable cone-jet mode. With this assembly, we have obtained poly(lactide-co-glycolide) microparticles with fine morphology and uniform size distribution. On the theoretical side, an instability analysis of the coaxial electrified jet has been performed based on the experimental parameters. The effects of process parameters on the formation of different unstable modes have been studied. The reported experimental and theoretical research represents a significant step toward quantitative control and optimization of the coaxial electrospray process for microencapsulation of multiple drugs and imaging agents in multimodal imaging and image-guided therapy.
Experimental and theoretical studies on coaxial atomization process of fabricating multifunctional microcapsules were
performed to overcome the limitation of commonly used microfabrication processes. The coaxial electrospray was first
developed, and then a novel process named coaxial electro-flow focusing which combined coaxial electrospray with
coaxial flow focusing was proposed. The process was characterized by the formation of a coaxial liquid jet in the core of
a high-speed co-flowing gas stream under an axial electric field and the breakup of the liquid jet into fine microcapsules.
The effects of main process parameters on the meniscus attached to the mouth of the coaxial needle were tested. A
theoretical model was further implemented for instability analysis of the coaxial jet to guide the process control and
optimization. As a result, stable cone-jet configurations in a wide range of process parameters and microcapsules with
good morphologies were obtained. The reported research represents the first step toward quantitative control and
optimization of the coaxial atomization process for the microfabrication of multifunctional microcapsules in multimodal
imaging and image-guided therapy.
Recent development in multimodal imaging and image-guided therapy requires multifunctional microparticles that
encapsulate several imaging and therapeutic agents in the same carrier for simultaneous detection and treatment of the
diseases. However, commonly used microfabrication processes for these microparticles have multiple limitations such as
the low encapsulation efficiency and the loss of bioactivity for the encapsulated biological cargos. To overcome these
limitations, we have carried out both the experimental and the theoretical studies on coaxial electrospray of
poly(lactide-co-glycolide) PLGA microparticles. On the experimental side, a coaxial electrospray setup has been
developed and tested. The setup consists of a customized coaxial needle assembly, two ring electrodes, two high-voltage
power supplies, two syringe infusion pumps, a particle collection reservoir, and a process monitoring system. On the
theoretical side, a classical normal mode method has been used for instability analysis of the coaxial electrified jet based
on the experimental parameters. The effects of different dimensionless process parameters on the formation of different
unstable modes have also been studied. The reported research represents the first step toward the quantitative control and
optimization of the coaxial electrospray process for the fabrication of multifunctional microparticles in multimodal
imaging and image-guided therapy.
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