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.
Anti-VEGF therapies have been widely explored for the management of posterior ocular disease, like neovascular
age-related macular degeneration (AMD). Loading anti-VEGF therapies in biodegradable microparticles may enable
sustained drug release and improved therapeutic outcome. However, existing microfabrication processes such as double
emulsification produce drug-loaded microparticles with low encapsulation rate and poor antibody bioactivity. To
overcome these limitations, we fabricate multifunctional microparticles by both single needle and coaxial needle
electrospray. The experimental setup for the process includes flat-end syringe needles (both single needle and coaxial
needle), high voltage power supplies, and syringe pumps. Microparticles are formed by an electrical field between the
needles and the ground electrode. Droplet size and morphology are controlled by multiple process parameters and
material properties, such as flow rate and applied voltage. The droplets are collected and freezing dried to obtain
multifunctional microparticles. Fluorescent beads encapsulated poly(DL-lactide-co-glycolide) acid (PLGA)
microparticles are injected into rabbits eyes through intravitreal injection to test the biodegradable time of microparticles.
We synthesize multifunctional microbubbles (MBs) for targeted delivery of antivascular endothelial growth factor (antiVEGF) therapy with multimodal imaging guidance. Poly-lactic-co-glycolic acid (PLGA) MBs encapsulating Texas Red dye are fabricated by a modified double-emulsion process. Simultaneous ultrasound and fluorescence imaging are achieved using Texas Red encapsulated MBs. The MBs are conjugated with Avastin, an antiVEGF antibody for treating neovascular age-related macular degeneration (AMD). The conjugation efficiency is characterized by enzyme-linked immunosorbent assay (ELISA). The efficiency for targeted binding of Avastin-conjugated MBs is characterized by microscopic imaging. Our work demonstrates the technical potential of using multifunctional MBs for targeted delivery of antiVEGF therapy in the treatment of exudative AMD.
Bevacizumab (Avastin) has been used as one of the anti-VEGF therapies to manage neovascular age-related macular degeneration (AMD). The drug delivery system for bevacizumab needs to be improved in order to decrease the frequency of injection and reduce the adverse effects. In our study, bevacizumab was conjugated with poly
(lactic-co-glycolic acid) (PLGA) microbubbles by activating carboxyl functional groups. The averaged size of microbubbles was estimated 1.055±0.258μm, allowing for ultrasound guided drug delivery. The binding efficiency between bevacizumab and microbubbles was evaluated in an enzyme-linked immunosorbent assay plate. The test results demonstrated the potential of using PLGA microbubbles to deliver bevacizumab with imaging guidance.
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