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Letters in Applied NanoBioScience. 03/2013;
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ABSTRACT: This work is focused on the fabrication of a new drug delivery system based on polyanionic matrix (e.g. sodium alginate), polycationic matrix (e.g. chitosan) and silica network. The FT-IR, SEM, DTA-TG, eukaryotic cell cycle and viability, and in vitro assay of the influence of the biocomposite on the efficacy of antibiotic drugs were investigated. The obtained results demonstrated the biocompatibility and the ability of the fabricated biocomposite to maintain or improve the efficacy of the following antibiotics: piperacillin-tazobactam, cefepime, piperacillin, imipenem, gentamicin, ceftazidime against Pseudomonas aeruginosa ATCC 27853 and cefazolin, cefaclor, cefuroxime, ceftriaxone, cefoxitin, trimethoprim/sulfamethoxazole against Escherichia coli ATCC 25922 reference strains.
International journal of pharmaceutics 11/2012; · 2.96 Impact Factor
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ABSTRACT: A novel, concise and efficient synthesis of substituted isocoumarins is disclosed. o-Allylbenzaldehydes prepared from isovanillin were mediated by PdCl(2)-CuCl(2) in water to undergo a domino reaction sequence, including 6-exo-trig cyclization, the addition of water, the elimination of PdHCl, the isomerization of carbon-carbon double bond, the oxidation of hemiacetals with the elimination of PdHCl, and regeneration of PdCl(2)in situ to yield a series of new substituted isocoumarins in high yields, in one pot.
Organic Letters 08/2012; 14(18):4930-3. · 5.86 Impact Factor
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ABSTRACT: 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.
Electrophoresis 06/2012; · 3.30 Impact Factor
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ABSTRACT: 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. 1,000μm 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.
KeywordsElectrostatic–Microcapsules–Encapsulation–Insulin–Monodisperse
04/2012; 1(4):289-298.
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ABSTRACT: 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.
PLoS ONE 01/2012; 7(3):e33184. · 4.09 Impact Factor
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ABSTRACT: 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.
Sensors 01/2012; 12(2):1455-67. · 1.74 Impact Factor
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ABSTRACT: 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 Fe(3)O(4) 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.
PLoS ONE 01/2012; 7(11):e49329. · 4.09 Impact Factor
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ABSTRACT: 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 rat's 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.
Biomaterials 11/2011; 33(5):1547-53. · 7.40 Impact Factor
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ABSTRACT: A temperature-controlled microfluidic approach was developed for fabricating monodispersed agar beads with the potential to be a brand-new strategy for cultivating Cordyceps militaris. The proposed microfluidic system features a circulating water bath with precise temperature control (temperature deviation ▵T<0.1°C). This device holds the promise of allowing us to develop a temperature-controlled system, characterized as simple, low cost, and easy to set up and use. The size-controllable agar beads were achieved by utilizing microfluidic emulsification in the cross-junction channel under temperature-controlled conditions. The flow conditions of the dispersed/continuous phases were adjusted to generate various sizes of agar beads. Our results show that the microparticles produced are as small as 176 μm with a 95% particle size distribution within 5 μm. The prepared agar microparticles performed well as a substrate for the cultivation of C. militaris. The proposed method could also be applied for encapsulating biomaterials, enzymes, drugs, catalysts, and nanoparticles into agar beads for biomedical applications.
Electrophoresis 11/2011; 32(22):3157-63. · 3.30 Impact Factor
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ABSTRACT: A number of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-6-{4-[3-(dimethylamino)propoxy]phenyl}-2-fluoro-9-hydroxy-11H-indeno[1,2-c]quinolin-11-one O-3-(dimethylamino)propyl oxime (23a) was the most active, exhibited GI(50) values of 0.64, 0.39, 0.55, 0.67, and 0.65μM against the growth of Hep G2, Hep 3B, A549, H1299, and MDA-MB-231, respectively. Compound 23a inhibited the growth of hepatoma cell lines in a dose- and time-dependent manner. The proportion of cells was decreased in the G1 and accumulated in G2/M phase after 12h treatment of 23a, while the hypodiploid (sub-G0/G1 phase) cells increased. Further investigations have shown that 23a induced cell cycle arrest at G2/M phase and induce apoptosis via activation of p53, Bax, and caspase-8 which consequently cause cell death.
Bioorganic & medicinal chemistry 10/2011; 19(24):7653-63. · 2.82 Impact Factor
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ABSTRACT: New gold nanorod (Au NR)-in-shell nanostructures were developed to be more efficacious than Au NRs in near-IR (NIR) hyperthermia and nonlinear optical imaging contrast. Au NR-in-shell nanostructures are composed of an intact Au NR in a Au/Ag nanoshell. These nanostructures have a broad, intense absorption band that extends from 400 nm to 900 nm in the NIR. They are more efficient and efficacious than Au NRs with respect to in vitro hypothermia performance. Au NR-in-shell-labeled cancer cells were destroyed using continuous-wave NIR radiation with 50% less laser power than needed for Au NRs. Noticeably, the area of the destroyed cells was significantly larger than the size of the laser irradiation beam; in contrast, the destroyed area was usually restricted to the size of the laser beam spot when Au NRs were used. With their extraordinarily broad and strong surface plasmon resonance band, Au NR-in-shell nanostructures efficiently augmented several multiphoton nonlinear processes as well. The multiphoton emission spectrum covered almost the entire visible wavelength. The yield of the multiphoton signals of Au NR-in-shell nanostructures was on average 55 times larger than that of Au NRs. In vitro images of cancer cells targeted by Au NR-in-shell nanostructures revealed a stronger multiphoton contrast than those targeted by Au NRs.
Journal of the American Chemical Society 09/2009; 131(40):14186-7. · 9.91 Impact Factor
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ABSTRACT: Based on the microfluidic emulsification process, the regular and stable formation of parent and satellite droplets can be achieved. The purpose of this study is to accurately separate the satellite (smaller) droplets from their parent (larger) droplets to obtain twin monodispersed microparticles by a bi-T-junction hybrid microchannels design controlling both emulsification and separation. Results show that both of the collected larger and smaller droplets are highly monodispersed (RSD Lt 2% and 6%, respectively), and featured with high reproducibility as well. This microfluidic device was also employed to present a facile one-step synthetic approach for the preparation of twin monodispersed alginate microparticles The proposed microfluidic chip is capable of generating relatively uniform twin microparticles with well controllable sizes, and it has the characteristics of a simple, low cost, and high throughput process. In the future this apparatus can be further applied to manufacture various twin monodispersed composite micro-vehicles to act as a smart drug delivery system.
Solid-State Sensors, Actuators and Microsystems Conference, 2009. TRANSDUCERS 2009. International; 07/2009
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ABSTRACT: This paper demonstrates a proof-of-concept approach for producing genipin-gelatin microcapsules of precisely controlled and monodisperse size distributions by the microfluidic channels. We have demonstrated that one could control the size of emulsions from 130 microm to 580 microm in diameter (with a variation of less than 5%) by altering the relative sheath/sample flow rate ratio. In addition, Results show that the encapsulation and in vitro release of a model drug, 5-fluorouracil, to enhance the effect of controlled release. We demonstrated that the appropriate particle size for different release patterns is predictable, enabling better application of genipin-gelatin microcapsules as a drug carrier. The proposed microfluidic chip is capable of generating relatively uniform micro-droplets with well controllable diameter, and it has the added advantages of being a simple, low cost, and high throughput process.
Journal of Controlled Release 04/2009; 137(1):15-9. · 5.73 Impact Factor
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ABSTRACT: A microfluidic device for generating monodisperse chitosan microparticles and separating the desired particle from smaller particles created as a byproduct of this process was described. The purpose of this study is to separate the satellite droplets from their parent droplets to enhance the size uniformity of the desired microparticles. A double T-junction design was first employed to control the emulsification and the separation, respectively. The results show that the size and gap of the parent droplets are tunable by adjusting the water and oil flow rates. A separation ratio of the satellite droplets of more than 99% was observed. The proposed microfluidic chip is capable of generating relatively uniform micro-droplets with well controllable diameter, and it has the added advantages of being a simple, low cost, and high throughput process. In the future this apparatus can be used to fabricate size-controlled monodisperse microparticles to act as drug carriers for biotechnology and biomedicine applications.
Lab on a Chip 02/2009; 9(1):145-50. · 5.67 Impact Factor
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ABSTRACT: This paper reports a novel immunoassay using an electro-microchip to detect the immuno-reaction signal, a gold nanoparticles (AuNPs) as a label of antigen or antibody and as a catalyst for silver precipitation, and the silver enhancement reaction to magnify the detection signal. The LCR meter instrument, a new detection method for immunoassay, is used to detect the electric single in a sandwich format. The change of the resistance to corroborate immuno-reaction is detected, amplified and analyzed to construct this new immunoassay. Different sizes of the electrodes are designed to discuss the relationship between gap size and sensitivity. In addition, the specificity, sensitivity and the detection limit of the electro-immunoassay are discussed. Using electro-microchip, nanoparticle and silver enhancement provided a new immunoassay method.
Industrial Electronics Society, 2007. IECON 2007. 33rd Annual Conference of the IEEE; 12/2007
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ABSTRACT: This study focuses on the design and experimental verification of an electroporation (EP) microchip system for the transfection of zebrafish (Danio rerio). For generating suitable pulses, a circuit is used to provide voltages between 0 and 700 V, with nearly 0-3,500 V/cm electric field. In addition, a proposed EP microchip, designed in a modular fashion, is fabricated using micro electromechanical system (MEMS) technology to allow for rapid and convenient replacement of each component. A numerical simulation is carried out to analyze the uniformity and strength of the EP electric fields generated in the microchip. Trypan blue dye, water-soluble quantum dots (MUA-QDs) and genes coding for green fluorescence protein (pEGFP-N1 plasmids) were employed to verify the successful delivery and transfection of zebrafish embryos. The experimental results show that the optimum delivery rate of trypan blue dyes and MUA-QDs were respectively up to 62 and 36% by using the proposed EP system. The successfully transfected embryos with the pEGFP-N1 plasmid used exhibit green fluorescence in the zebrafish embryos. The approach in the transfection of zebrafish embryos will provide many potential usages for cellular imaging areas, gene therapy research and medical applications.
Biomedical Microdevices 11/2007; 9(5):761-8. · 3.03 Impact Factor
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ABSTRACT: This study has demonstrated the optimization of an electroporation (EP) system for gene transfection by using the Taguchi method. The parameters of the EP system, which could have an influence on the transecting rate, were optimized, resulting in values of 50 mum electrode gap, 80 mug/mL pEGFP-Nl concentration, 6 V pulse voltage, and 2-pulse. A larger-the-better Omega transformation was employed for better additivity. The analyzed results of interaction A times C, A times D, and C times D showed that there were strong interactions on level 3 of factors A, C, and D to each others. Using optimized EP system, the pEGFP-Nl plasmid was successfully transfected into the basal cell carcinoma cell line (BCC) with 40.36% average transecting rate.
Solid-State Sensors, Actuators and Microsystems Conference, 2007. TRANSDUCERS 2007. International; 07/2007
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ABSTRACT: This paper demonstrates a proof-of-concept approach for encapsulating CdSe/ZnS quantum dots (QDs) into uniform-sized poly(DL-lactide-co-glycolide) (PLGA) biocompatible microcapsules utilizing a microfluidic chip. By adapting a blend of poly(vinyl alcohol) (PVA) and chitosan (CS) as stabilizers for constructing a PLGA polymer matrix to entrap CdSe/ZnS QDs, the PLGA polymer solution was constrained to adopt the spherical droplets in a continuous aqueous phase at a microchannel cross-junction. The generation of these droplets was then studied quantitatively. The flow conditions of the two immiscible solutions were adjusted in order to successfully generate the polymer droplets. Size-controllable PLGA microgels containing CdSe/ZnS QDs were produced, ranging in size from 180 to 550 µm in diameter. The narrow size distribution (within ± 5%) was obtained by altering the ratio of the flow rate. In contrast to individual QDs, each PLGA microsphere encapsulates thousands of fluorescent QDs in a protective polymer matrix, providing a highly amplified and reproducible signal for fluorescence-based bioanalysis.
Nanotechnology 06/2007; 18(30):305305. · 3.98 Impact Factor
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ABSTRACT: This paper describes the generation of monodisperse calcium alginate (Ca-alginate) microcapsules on a microfluidic platform using the commercial optical disk process. Our strategy is based on combining the rapid injection molding process for a cross-junction microchannel with the sheath focusing effect to form uniform water-in-oil (w/o) emulsions. These emulsions, consisting of 1.5% (w/v) sodium alginate (Na-alginate), are then dripped into a solution containing 20% (w/v) calcium chloride (CaCl2) creating Ca-alginate microparticles in an efficient manner. This paper demonstrates that the size of Ca-alginate microparticles can be controlled from 20 µm to 50 µm in diameter with a variation of less than 10%, simply by altering the relative sheath/sample flow rate ratio. Experimental data show that for a given fixed dispersed phase flow (sample flow), the emulsion size decreases as the average flow rate of the continuous phase flow (sheath flow) increases. The proposed microfluidic platform is capable of generating relatively uniform emulsions and has the advantages of active control of the emulsion diameter, a simple and low cost process and a high throughput.
Journal of Micromechanics and Microengineering 06/2007; 17(8):1428. · 2.11 Impact Factor
