• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.147-151
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• 2011

This paper demonstrates the development of a method for preparing micropatterned microdiscs in order to increase contact area with cells and to change the release pattern of drugs. The microdiscs were manufactured with hot embossing, where a polyurethane master structure was pressed onto both solid and porous microparticles made of polylactic-co-glycolic acid at various temperatures to form a micropattern on the microdiscs. Flat microdiscs were formed by hot embossing of porous microparticles; the porosity allowed space for flattening of the microdiscs. Three types of micro-grooves were patterned onto the flat microdiscs using prepared micropatterned molds: (1) 10 ${\mu}M$ deep, 5 ${\mu}M$ wide, and spaced 2 ${\mu}M$ apart; (2) 10 ${\mu}M$ deep, 9 ${\mu}M$ wide, and spaced 5 ${\mu}M$ apart; and (3) 10 ${\mu}M$ deep, 50 ${\mu}M$ wide, and spaced 50 ${\mu}M$ apart. This novel microdisc preparation method using hot embossing to create micropatterns on flattened porous microparticles provides the opportunity for low-cost, rapid manufacture of microdiscs that can be used to control cell adhesion and drug delivery rates.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2016.11a
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• pp.105-105
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• 2016

Recently, high power impulse magnetron sputtering (HIPIMS) has attracted considerable attentions due to its high potential for industrial applications. By pulsing the sputtering target with high power density and short duration pulses, a high plasma density and high ionization of the sputtered species can be obtained. HIPIMS has exhibited several merits such as increased coating density, good adhesion, microparticle-free and smooth surface, which make the HIPIMS technique desirable for synthesizing hard coatings. However, hard coatings present intrinsic defects (columnar structures, pinholes, pores, discontinuities) which can affect the corrosion behavior, especially when substrates are active alloys like steel or in a wear-corrosion process. Atomic layer deposition (ALD), a CVD derived method with a broad spectrum of applications, has shown great potential for corrosion protection of high-precision metallic parts or systems. In ALD deposition, the growth proceeds through cyclic repetition of self-limiting surface reactions, which leads to the thin films possess high quality, low defect density, uniformity, low-temperature processing and exquisite thickness control. These merits make ALD an ideal candidate for the fabrication of excellent oxide barrier layer which can block the pinhole and other defects left in the coating structure to improve the corrosion protection of hard coatings. In this work, CrN/Al2O3/CrN multilayered coatings were synthesized by a hybrid process of HIPIMS and ALD techniques, aiming to improve the CrN hard coating properties. The influence of the Al2O3 interlayer addition, the thickness and intercalation position of the Al2O3 layer in the coatings on the microstructure, surface roughness, mechanical properties and corrosion behaviors were investigated. The results indicated that the dense Al2O3 interlayer addition by ALD lead to a significant decrease of the average grain size and surface roughness and greatly improved the mechanical properties and corrosion resistance of the CrN coatings. The thickness increase of the Al2O3 layer and intercalation position change to near the coating surface resulted in improved mechanical properties and corrosion resistance. The mechanism can be explained by that the dense Al2O3 interlayer acted as an excellent barrier for dislocation motion and diffusion of the corrosive substance.

• Korean Journal of Clinical Pharmacy
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• v.18 no.1
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• pp.60-67
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• 2008

This study aimed to compare a microparticle enzyme immunoassay (MEIA) with a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for the measurement of tacrolimus concentrations in adult liver transplant recipients, to investigate how the assay choice influenced the population pharmacokinetics of tacrolimus and to identify patient characteristics that affected pharmacokinetic parameters in each assay. Tacrolimus concentrations from 29 liver (n=52 paired-samples) transplant recipients measured by both MEIA and LC/MS/MS were used to evaluate the performance of these methods in the clinical setting. Tacrolimus pharmacokinetics was studied independently using MEIA and LC/MS/MS data in 70 adult patients using a population approach performed with NONMEM. Patient characteristics which influenced pharmacokinetic parameters in each assay were compared. The relation between LC/MS/MS and MEIA measurements was best described by the regression equation MEIA=1.465*LC/MS/MS-1.336 (r=0.91). Multiple linear regression analysis showed significant inverse relationships between assay difference and hematocrit (Hct) (p<0.025) in liver graft recipients. In MEIA, the population estimate of tacrolimus CL/F and apparent volume of distribution (Vd/F) were found to be 10.1 L/h and 226 L, and in LC/MS/MS, 13 L/h and 305 L respectively. Neither patient's age, weight, gender, grafted hepatic weight, albumin concentration, nor markers of liver function influenced tacrolimus CL/F The final model of CL/F was found to be 10.1+(Hct/Hct mean)$^{12.0}$ in MEIA and 13+(1+Hct/578) in LC/MS/MS indicating that CL/F was influenced by hematocrit.

• Korean Chemical Engineering Research
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• v.56 no.5
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• pp.761-766
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• 2018

Droplet-based microfluidic device has led to transformational new approaches in various applications including materials synthesis and high-throughput screening. However, efforts are required to enhance the production rate to industrial scale because of low production rate in a single droplet generator. In here, we present a method for enhancing production rate of monodisperse droplets via parallelization of flow-focusing generators. For this, we fabricated a three-dimensional monolithic elastomer device (3D MED) that has the 3D channel structures in a single layer, using a double-sided imprinting method. We demonstrated that the production rate of monodisperse droplet is increased by controlling the flow rate of continuous and dispersed phases in 3D MED with 8 droplet generators. Thus, we anticipate that this microfluidic system will be used in wide area including microparticle synthesis and screening system via encapsulation of various materials and cells in monodisperse droplets.

• The Journal of Advanced Prosthodontics
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• v.2 no.1
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• pp.7-13
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• 2010

Although most researchers agree that platelet-rich plasma (PRP) is a good source of autogenous growth factors, its effect on bone regeneration is still controversial. The purpose of this study was to evaluate whether increasing angiogenic factors in the human PRP to enhance new bone formation through rapid angiogenesis. MATERIAL AND METHODS. In vitro, the human platelets were activated with application of shear stress, $20\;{\mu}g/ml$ collagen, 2 mM $CaCl_2$ and 10U thrombin/$1\;{\times}\;10^9$ platelets. Level of vascular endothelial growth factor (VEGF) and platelet microparticle (PMP) in the activated platelets were checked. In the animal study, human angiogenic factors-enriched PRP was tested in 28 athymic rat's cranial critical bone defects with $\beta$-TCP. Angiogenesis and osteogenesis were evaluated by laser Doppler perfusion imaging, histology, dual energy X-ray densinometry, and micro-computed tomography. RESULTS. In vitro, this human angiogenic factors-enriched PRP resulted in better cellular proliferation and osteogenic differentiation. In vivo, increasing angiogenic potential of the PRP showed significantly higher blood perfusion around the defect and enhanced new bone formation around acellular bone graft material. CONCLUSION. Angiogenic factor-enriched PRP leads to faster and more extensive new bone formation in the critical size bone defect. The results implicate that rapid angiogenesis in the initial healing period by PRP could be supposed as a way to overcome short term effect of the rapid angiogenesis.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.99-104
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• 2008

PLGA micro/nano particles encapsulating ranitidine as a hydrophilic model drug were prepared by the double-emulsion solvent evaporation method. Surface morphology investigation by scanning electron microscope (SEM) showed that the emulsification by sonication could produce nanoparticles, whereas microparticles were prepared using high speed homogenizer. Moreover, while nanohalf-shell structure instead of spherical nanoparticle could be produced by adding poloxamer into oil phase (MC) with PLGA 504H, the addition of poloxamer didn't change particle shape in case of PLGA 502H. On the other hand, microparticle with poloxamer had more surface pores than those without poloxamer. The size and polydispersity (PDI) of particles were determined by particle size analyzer. Effective diameters of particles were in the range of $400{\sim}800\;nm$ and $1200{\sim}3300\;nm$ in case of nanoparticles and microparticles, respectively. Encapsulation efficiencies were in the range of $1.2{\sim}2.9%$. The addition of poloxamer produced the particles with higher encapsulation efficiency. In vitro release study in phosphate buffer (pH 7.4) at $37^{\circ}C$ showed common large initial burst release. However, the relative slower release profile could be observed in case of microparticles. Poloxamer addition increased the release rate, which was thought to be related to the increased surface area of particles.

• Journal of the Korean Society for Aeronautical & Space Sciences
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• v.36 no.6
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• pp.587-593
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• 2008

Transdermal and topical drug delivery with minimal tissue damage has been an area of vigorous research for years. Our research team has initiated the development of an effective method for delivering drug particles across the skin (transdermal) for systemic circulation, and to localized (topical) areas. The device consists of a laser ablation based micro-particle acceleration system that can be integrated with endoscopic surgical techniques. We have successfully delivered 3μm size cobalt particles into gelatin models that represent soft tissue with remarkable penetration depth.

• Journal of Microbiology and Biotechnology
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• v.31 no.8
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• pp.1088-1097
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• 2021

Grouper nervous necrosis virus (GNNV) infection causes mass grouper mortality, leading to substantial economic loss in Taiwan. Traditional methods of controlling GNNV infections involve the challenge of controlling disinfectant doses; low doses are ineffective, whereas high doses may cause environmental damage. Identifying potential methods to safely control GNNV infection to prevent viral outbreaks is essential. We engineered a virus-binding bacterium expressing a myxovirus resistance (Mx) protein on its surface for GNNV removal from phosphate-buffered saline (PBS), thus increasing the survival of grouper fin (GF-1) cells. We fused the grouper Mx protein (which recognizes and binds to the coat protein of GNNV) to the C-terminus of outer membrane lipoprotein A (lpp-Mx) and to the N-terminus of a bacterial autotransporter adhesin (Mx-AIDA); these constructs were expressed on the surfaces of Escherichia coli BL21 (BL21/lpp-Mx and BL21/Mx-AIDA). We examined bacterial surface expression capacity and GNNV binding activity through enzyme-linked immunosorbent assay; we also evaluated the GNNV removal efficacy of the bacteria and viral cytotoxicity after bacterial adsorption treatment. Although both constructs were successfully expressed, only BL21/lpp-Mx exhibited GNNV binding activity; BL21/lpp-Mx cells removed GNNV and protected GF-1 cells from GNNV infection more efficiently. Moreover, salinity affected the GNNV removal efficacy of BL21/lpp-Mx. Thus, our GNNV-binding bacterium is an efficient microparticle for removing GNNV from 10‰ brackish water and for preventing GNNV infection in groupers.

• Korean Chemical Engineering Research
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• v.60 no.1
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• pp.139-144
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• 2022

This study reports a microfluidic approach to produce monodisperse hydrogel microparticles in a simple and highly efficient manner. Specifically, we produce double emulsion drops with a thin oil shell surrounding an aqueous prepolymer solution, which is solidified via UV-induced free radical polymerization. When they are dispersed in an aqueous solution, the oil shell is dewetted due to the absence of surfactants, resulting in production of highly uniform hydrogel microparticles (C.V.=1%). Results show that production of monodisperse hydrogel microparticles with controllable size and composition can be achieved with minimal use of oil unlike water-in-oil (w/o) single emulsion-based approach. Furthermore, in-depth study of flow patterns in microfluidic device using a phase diagram exhibits a crucial relationship among relative flow rates while providing windows of readily controllable parameters for reliable manufacturing of hydrogel microparticles.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.210-218
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• 2023

Prostate cancer is the fifth leading cause of cancer-related mortality in men, primarily because of treatment resistance, recurrence, and metastasis. In the present study, we investigated the role of paracrine interleukin-8 (IL-8) in the antagonistic expression of IL-8 and androgen receptor (AR), and the contribution of IL-8 to prostate cancer aggressiveness. In hormone-responsive LNCaP cells that do not express IL-8, recombinant IL-8 treatment significantly increased expressions of IL-8, CXC chemokine receptor 2 (CXCR2), matrix metalloproteinase (MMP)-2/9, Snail, and vimentin. IL-8 treatment significantly decreased AR and E-cadherin expression. IL-8-induced gene expression changes were suppressed by navarixin, a CXCR1/2 inhibitor, and gallein, a Gβγ inhibitor. In PC-3 androgen-refractory prostate cancer cells, IL-8 knockdown reduced expressions of CXCR2, MMP-2/9, Snail, and vimentin, and increased AR and E-cadherin expressions at the mRNA and protein levels. Co-culture with MEG-01 human megakaryocytic cells secreting high levels of IL-8 induced gene expression changes in both LNCaP and PC-3 cells, similar to those induced by IL-8 treatment. The altered gene expressions were accompanied by significant activation of transcription factor Snail in LNCaP and PC-3 cells. Treatment with the CXCR blocker navarixin inhibited the invasion of PC-3 cells but not LNCaP cells. However, invasion induced by MEG-01 was inhibited by navarixin in both LNCaP and PC-3 cells. The collective findings demonstrate that IL-8 enhances CXCR2 expression, which antagonistically regulates AR expression. More importantly, through changes in IL-8/CXCR2-regulated gene expression, IL-8 induces antiandrogen therapy resistance and epithelial-mesenchymal transition in prostate cancer.