Chih-Yu Wang

Anti-inflammatory effect with high intensity focused ultrasound-mediated pulsatile delivery of diclofenac.

A pulsatile ultrasound controlled drug release platform with diclofenac-loaded alginate microcapsules (fabricated with a home-made electrostatic device, 75% embedded rate) was established to evaluate anti-inflammation efficiency. Better anti-inflammation efficiency was found using the ultrasound system and the drug delivery can be adjusted based on the programmed ultrasound cycle. The results of the in vitro study show that an approx. 30% higher drug release rate was obtained by using continuous ultrasound irradiation (9-Watt, 180 min), and an approx. 16% higher drug release rate was obtained by using pulsatile ultrasound irradiation (9-Watt, 60 min) compared to without ultrasound activation. For the in vivo study, the anti-inflammatory test with carrageenan-induced rats paw edema shows that diclofenac-loaded microcapsules followed by ultrasound irradiation (9-Watt, 60 min) contributed to an 81% inhibition rate, which was significantly higher than diclofenac only (approx. 60% higher). In addition, because of their heat conducting properties, gold nanoparticles encapsulated in the diclofenac-loaded microcapsules resulted in better drug release efficiency, but tended to depress the anti-inflammation effect.

Microfluidic Synthesis of Microfibers for Magnetic-Responsive Controlled Drug Release and Cell Culture

This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture.

Synthesis and anti-fungal effect of silver nanoparticles–chitosan composite particles

Silver nanoparticles have been used in various fields, and several synthesis processes have been developed. The stability and dispersion of the synthesized nanoparticles is vital. The present article describes a novel approach for one-step synthesis of silver nanoparticles–embedded chitosan particles. The proposed approach was applied to simultaneously obtain and stabilize silver nanoparticles in a chitosan polymer matrix in-situ. The diameter of the synthesized chitosan composite particles ranged from 1.7 mm to 2.5 mm, and the embedded silver nanoparticles were measured to be 15±3.3 nm. Further, the analyses of ultraviolet-visible spectroscopy, energy dispersive spectroscopy, and X-ray diffraction were employed to characterize the prepared composites. The results show that the silver nanoparticles were distributed over the surface and interior of the chitosan spheres. The fabricated spheres had macroporous property, and could be used for many applications such as fungicidal agents in the future.

An Aluminum Microfluidic Chip Fabrication Using a Convenient Micromilling Process for Fluorescent Poly(DL-lactide-co-glycolide) Microparticle Generation

This study presents the development of a robust aluminum-based microfluidic chip fabricated by conventional mechanical micromachining (computer numerical control-based micro-milling process). It applied the aluminum-based microfluidic chip to form poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating CdSe/ZnS quantum dots (QDs). A cross-flow design and flow-focusing system were employed to control the oil-in-water (o/w) emulsification to ensure the generation of uniformly-sized droplets. The size of the droplets could be tuned by adjusting the flow rates of the water and oil phases. The proposed microfluidic platform is easy to fabricate, set up, organize as well as program, and is valuable for further applications under harsh reaction conditions (high temperature and/or strong organic solvent systems). The proposed method has the advantages of actively controlling the droplet diameter, with a narrow size distribution, good sphericity, as well as being a simple process with a high throughput. In addition to the fluorescent PLGA microparticles in this study, this approach can also be applied to many applications in the pharmaceutical and biomedical area.

Electrostatic droplets assisted synthesis of alginate microcapsules

This paper demonstrates a proof-of-concept approach for encapsulating the insulin and Fe3O4 nanoparticles into size-controllable alginate microcapsules utilizing the electrostatic droplets (ESD) technique. We have established that the combination of ESD and external gelation is quite effective in producing uniform-sized polymer particles. In addition, using the external gelation technique, the droplets containing a sodium-alginate were gelled in situ by immersion in Ca2+, Ba2+, or Cu2+ ions for a few minutes. The results show that different-type divalent cations caused various surface features to appear on the microcapsules (e.g., cracking, orange peel, pitting, splitting, wrinkling, etc.). The particle size can be adjusted from a few micrometers to ca. 1,000xa0μm by electrostatic force. The microcapsules can be made magnetic by incorporating a super-paramagnetic nanomaterial (e.g., Fe3O4 nanoparticles) during the preparation. The composite magnetic microcapsules are potential candidates for a magnetic-responsive drug delivery system. In addition, our results show that the encapsulation and in vitro release of a model drug, insulin, can enhance the effect of the controlled release. These microcapsules are addressable by an external magnetic field and are capable of loading a model drug and releasing it in a highly differential drug release profile. We have demonstrated that the appropriate magnetic field intensity for different release patterns is predictable, which enables a better application of microcapsules as a smart drug carrier.

Microfluidic-assisted synthesis of hemispherical and discoidal chitosan microparticles at an oil/water interface

This study reports a facile method for the synthesis of hemispherical and discoidal chitosan microparticles by a combination of microfluidic technology and gelation strategy at an oil/water interface. Utilizing microfluidic emulsification in a cross‐junction channel, the formation of regular droplets was achieved. Following the ionic gelation procedure at the liquid–liquid interface of the gelling solution and oil solution in the reservoir pool, either hemispherical or discoidal chitosan microparticles were obtained. Special emphasis was put on the interface reaction of emulsion gelation parameters such as ionic crosslinkers, density modifiers, and surfactants, to tailor the morphologies of chitosan particles ranging from 160 to 750 μm. In addition, the proposed microfluidic device is capable of generating relatively uniform microparticles with a well‐controllable shape and size. Being a simple, low‐cost and high‐throughput process is an added advantage. The synthesized hemispherical and discoidal chitosan microparticles can be applied to many applications in the pharmaceutical and biomedical arena.

Microfluidic one-step synthesis of Fe3O4-chitosan composite particles and their applications

This paper demonstrates a simple and easy approach for the one-step synthesis of Fe₃O₄-chitosan composite particles with tadpole-like shape. The length and diameter of the particles were adjustable from 638.3 μm to ca. 798 μm (length), and from 290 μm to 412 μm (diameter) by varying the flow rate of the dispersed phase. Mitoxantrone was used as the model drug in the drug release study. The encapsulation rate of the drug was 71% for chitosan particles, and 69% for magnetic iron oxide-chitosan particles, respectively. The iron oxide-chitosan composite particles had a faster release rate (up to 41.6% at the third hour) than the chitosan particles (about 24.6%). These iron oxide-chitosan composite particles are potentially useful for biomedical applications, such as magnetic responsive drug carriers, magnetic resonance imaging (MRI) enhancers, in the future.

Facile Synthesis of Radial-Like Macroporous Superparamagnetic Chitosan Spheres with In-Situ Co-Precipitation and Gelation of Ferro-Gels

Macroporous chitosan spheres encapsulating superparamagnetic iron oxide nanoparticles were synthesized by a facile and effective one-step fabrication process. Ferro-gels containing ferrous cations, ferric cations and chitosan were dropped into a sodium hydroxide solution through a syringe pump. In addition, a sodium hydroxide solution was employed for both gelation (chitosan) and co-precipitation (ferrous cations and ferric cations) of the ferro-gels. The results showed that the in-situ co-precipitation of ferro-ions gave rise to a radial morphology with non-spheroid macro pores (large cavities) inside the chitosan spheres. The particle size of iron oxide can be adjusted from 2.5 nm to 5.4 nm by tuning the concentration of the sodium hydroxide solution. Using Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra, the synthesized nanoparticles were illustrated as Fe3O4 nanoparticles. In addition, the prepared macroporous chitosan spheres presented a super-paramagnetic behaviour at room temperature with a saturation magnetization value as high as ca. 18 emu/g. The cytotoxicity was estimated using cell viability by incubating doses (0∼1000 µg/mL) of the macroporous chitosan spheres. The result showed good viability (above 80%) with alginate chitosan particles below 1000 µg/mL, indicating that macroporous chitosan spheres were potentially useful for biomedical applications in the future.

Core-shell structure microcapsules with dual pH-responsive drug release function

We report dual pH‐responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce monodisperse core (alginate)‐shell (chitosan) structure with dual pH‐responsive drug release function. The fabricated core‐shell microcapsules were size controllable by tuning the synthesis parameters of the ESD and MFD systems, and were responsive in both acidic and alkaline environment, We used two model drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the alginate core) for drug delivery study. The results show that core‐shell structure microcapsules have better drug release efficiency than respective core or shell particles. A biocompatibility test showed that the core‐shell structure microcapsules presented positive cell viability (above 80%) when evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results indicate that the synthesized core‐shell microcapsules were a potential candidate of dual‐drug carriers.

Synthesis of uniform core–shell gelatin–alginate microparticles as intestine‐released oral delivery drug carrier

A core–shell gelatin–alginate composite used for intestine‐released oral delivery drug carrier was synthesized through microfluidic technique. At the fixed continuous phase flow rate, the size of the core–shell gelatin–alginate microparticles increases with the dispersed phase flow rate, and monodispersity can be retained (the variation coefficient for the diameter distribution can be kept less than 10%). The fabricated microparticles could remain intact in gastric juice for at least 3 h, indicating that the gelatin core could be well protected by alginate shell in acid environment. However, the alginate shell of the microparticles would swell or collapse in alkali environment in half an hour, assuring the controlled drug release in intestinal juice. The fabricated uniform core–shell gelatin–alginate microparticles were potential as pH‐responsive drug carriers.