• Journal of Pharmaceutical Investigation
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• 제29권3호
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• pp.171-177
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• 1999

Lidocaine(2-Diethylaminoaceto-2', 6'-xylidide) was transdennally delivered by iontophoresis and the effect of enhancer on the delivery of lidocaine was studied. We delivered lidocaine through the skin of hairless mouse using diffusion cell and investigated the effect of the amount of cation salts such as sodium chloride, calcium acetate, zinc acetate and aluminum acetate on the drug delivery. The amounts of transported drugs and adsorbed metal ions were measured by HPLC(High Perfonnance Liquid Chromatography) and AAS(Atomic Absorption Spectrophotometry), respectively. The addition of zinc acetate and aluminum acetate greatly enhanced the delivery of lidocaine. The detection of two metal ions by AAS seemed to support the idea that the astringency effect of these ions were the main reason for the enhancement of transdermal delivery.

• 공업화학
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• 제32권5호
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• pp.556-561
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• 2021

최근 산화철 나노입자는 외부의 자기장에 반응하는 자성의 특성과 생체적합성이 뛰어나 약물전달시스템(drug delivery system, DDS)에 관한 많은 연구의 소재로 사용되어져 왔다. 본 연구에서는 마이크로니들(microneedles, MNs)의 매트릭스 물질로 HA (hyaluronic acid)와 CMC (carboxy methyl cellulose)를 이용하여 SIONs (superparamagnetic iron oxide nanoparticles)이 함유된 HA-SMNs (hyaluronic acid-superparamagnetic microneedles)와 CMC-SMNs (carboxy methyl cellulose-superparamagnetic microneedles)를 제조하였으며, SEM (scanning electron microscopic), SQUD-VSM (superconducting quantum interference device-vibrating sample magnetometer), FMMD (frequency mixing magnetic detection), 고분자 및 바이오 멤브레인을 이용하여 SMNs의 다양한 특성을 조사하였다. SQUID-VSM 측정 결과 SIONs이 포함된 HA-SMNs와 CMC-SMNs에서 초상자성의 특성이 나타났으며, FMMD 측정에서는 SIONs 농도가 증가함에 따라 신호 강도에 변화가 확인되었다. 또한 SMNs의 바이오 막을 통한 HA-SMNs와 CMC-SMNs의 투과도 분석에서는 각각 평균 92.5%와 98.5%의 피부 투과율이 조사되었다. 이러한 결과를 통해 SMNs 제형은 경피약물전달시스템(transdermal drug delivery system, TDDS) 및 MR(magnetic mesonance) molecular imaging 분야의 전달소재로 활용될 수 있을 것으로 기대한다.

• 공업화학
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• 제35권5호
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• pp.423-428
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• 2024

마이크론 크기의 미세바늘 배열로 구성된 마이크로니들은 최소 침습성 통증으로 활성 의약품 성분을 경피 투여하기 위한 새로운 기술이다. 지난 수년간 마이크로니들의 구조를 정확히 제조하기 위해 다양한 적층 제조 기술이 사용되었지만 기존의 기술은 시간과 비용이 많이 드는 것뿐만 아니라 제한적인 재료 호환성과 생체 이용률에 대한 한계성이 있었다. 본 연구에서는 생분해성 PCLDA/PEGDA 마이크로니들의 정확한 제조를 위해 Polyjet과 DLP-SLA 3D 프린팅 방법의 해상도를 비교하였다. 두 3D 프린팅 방식을 기반으로 마이크로니들의 구조적 정확성을 향상시키기 위해 3D 프린팅 각도, 바늘 높이 및 직경을 포함한 3D 프린팅 조건을 비교 및 평가하였다. 최적화된 3D 프린팅 조건을 적용하여 날카로운 바늘 끝을 가진 마이크로니들 몰드를 제작하였으며, 복제 성형 공정을 통해 고분자 마이크로니들을 제작하였다. 최종적으로, 광경화성 PCLDA와 PEGDA를 이용한 생분해성/생체적합성 마이크로니들을 제작하였으며, PCLDA 농도에 따른 기계적 특성 제어를 통해 피부 삽입에 필요한 강도를 평가하였다. 본 연구에서는 3D 프린팅을 이용해 고해상도 마이크로니들을 저비용 및 효율적으로 제작하여 경피 약물 전달 분야에 응용할 수 있음을 증명하였다.

• 대한기계학회논문집A
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• 제28권12호
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• pp.1871-1876
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• 2004

We demonstrate a novel fabrication technology for the microneedle array that can be used in the medical test field, which is transdermal drug delivery and blood analyte sampling. Previous researchers have used silicon-processed micromachining, a reactive ion etching, and molding techniques for the fabrication of microneedle array. However, these fabrication techniques have somewhat limitations apply to the microneedle array fabrication according to its application. Inclined LIGA process is suggested to overcome these problems. This process provides easier, sharper and longer out-of-plane microneedle array structure than conventional silicon-processed fabrication method did. Additionally, because of the advantage of the LIGA process based on mold fabrication for mass production, the polymer, PMMA(PolyMethylMethAcrylate), based microneedle array is useful as the mold base of nickel electroplating process; on the other hand, silicon-processed microneedle array is used in itself. In this research, we fabricate different types of out-of-plane microneedle array, which have different shape of tip, base and hole structure, using the inclined LIGA process. The fabricated microneedles have proper mechanical strength, height and sharpness to puncture human hand epidermis or dermis with less pain and without needle tip break during penetrating the skin.

• Translational and Clinical Pharmacology
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• 제25권1호
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• pp.15-20
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• 2017

This study was performed to evaluate the use of vibrating microneedles for the transdermal delivery of vitamin C. The microneedles were designed to vibrate at three levels of intensity. In vitro permeation by vitamin C was evaluated according to the specific conditions such as vibration intensity (levels 1, 2 and 3), application time (1, 3, 5, 7 and 10 min), and application power (500, 700 and 1,000 g). The highest permeation of vitamin C was observed at level 3 of vibration intensity, 5 min of application, and 1,000 g of application power. Vitamin C gel showed no cytotoxic effect against Pam212 cells or skin irritation effects. A pharmacokinetic study of the gel in rats was conducted under optimized conditions. The $AUC_{0-{\infty}}$ and $C_{max}$ increased 1.35-fold and 1.44-fold, respectively, compared with those after vitamin C gel without application with vibrating microneedles. The present study suggests that vibrating microneedles can be used to facilitate the skin permeability of vitamin C under optimal conditions.

• Journal of Pharmaceutical Investigation
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• 제32권4호
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• pp.313-319
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• 2002

Rat skin permeation of various nonsteroidal antiinflammatory drugs (NSAIDs) was investigated in vitro using Franz diffusion cell at $37^{\circ}C$. The effect of various skin permeation enhancers was also observed as a preliminary study of developing transdermal delivery systems of NSAIDs. Lipophilicity of NSAIDs was determined from thε partition coefficient (log P) in 1-octanol/water and 1-octanol/IPB mutual-saturated solutions. The solubility was determined in water, isotonic phosphate buffer (IPB), and propylene glycol (PG) at $37^{\circ}C$. The rat skin permeation rate of acetaminophen, piroxicam, and aceclofenac was almost negligible, although they were saturated in PG. Addition of 1 % permeation enhancer increased the permeation rate of ketoprofen, ketorolac, and diclofenac. However, the skin permeation rate of ibuprofen did not increase with the addition of various enhancers. Among the permeation enhancers testεd, oleic acid was the most effective for various NSAIDs. Based on the daily dose, lipophilicity, and the skin permeation ratε achieved in this study, ketoprofen and ketorolac seem to be the most promising drug candidates for transdermal delivery systems, especially when formulated with unsaturated fatty acids, such as oleic acid.

• Korean Chemical Engineering Research
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• 제46권2호
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• pp.211-216
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• 2008

아토피의 치료를 위해 사용되는 부펙사막은 연고제 형태로 사용되는 약물이다. 부펙사막은 피부 장벽효과에 의해 실제 전달되는 양은 매우 적다. 이러한 문제를 갖는 부펙사막의 피부전달 효율을 증가시키기 위하여 마이크로니들을 이용해 피부처리를 실시하였다. 약물의 피부투과량과 피부에서 약물의 전달형태를 알아보기 위하여 부펙사막에 FITC를 결합시켰으며 이를 포함하는 하이드로겔을 제조하여 피부에 도포하였다. 약물의 피부투과량을 확인하기 위해서 형광분광계를 사용하여 분석하였으며 약물의 전달형태를 확인하기 위하여 형광필터가 장착된 마이크로현미경을 사용하였다. 실험결과 마이크로니들로 처리된 피부에서 부펙사막의 피부투과량이 대조군에 비해 5~20배 이상 증가되었으며 마이크로니들 처리횟수가 증가함에 따라서 더 크게 증가될 수 있음을 확인하였다.

• Journal of Pharmaceutical Investigation
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• 제36권5호
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• pp.321-329
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• 2006

Albuterol, a selective ${\beta}_2$-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of albuterol sulfate was investigated in hairless mouse skin in vitro with and without pretreatment with enhancers. The enhancing effects of ethanol and various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, and fatty acids on the permeation of albuterol sulfate were evaluated using Franz diffusion cells. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of albuterol sulfate approximately 33-fold compared with the control without enhancer pretrement, followed by d-limonene with enhancement ratio of 21.79. 2-Pyrrolidone-5-carboxylic acid increased the permeability of albuterol sulfate approximately 5.5-fold compared with the control. Other pyrrolidones tested showed only slight permeability enhancing effect with enhancement ratio less than 2.8. Nonionic surfactants showed moderate enhancing effects. Lauric acid increased the permeability of albuterol sulfate approximately 30-fold with decreasing the lag time from 2.85 to 0.64 hr. Oleic acid and linoleic acid showed enhancement ratio of 24.55 and 22.91, respectively. These findings would allow a more rational approach for designing formulations for the transdermal delivery of albuterol sulfate and similar drugs.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2014년도 제46회 동계 정기학술대회 초록집
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• pp.411.1-411.1
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• 2014

This study evaluates the utility of an antibacterial microneedle composed of green tea extract (GT) and hyaluronic acid (HA), for the efficient delivery of GT. These microneedles have the potential to be a patient-friendly method for the conventional sustained release of drugs. In this study, a fabrication method using a mold-based technique to produce GT/HA microneedles with a maximum area of ${\sim}60mm^2$ with antibacterial properties was used to manufacture transdermal drug delivery systems. Fourier transform infrared (FTIR) spectrometry was carried out to observe the potential modifications in the microneedles, when incorporated with GT. The degradation rate of GT in GT/HA microneedles was controlled simply by adjusting the HA composition. The effects of different ratios of GT in the HA microneedles were determined by measuring the release properties. In HA microneedles loaded with 70% GT (GT70), a continuous higher release rate were sustained for 72 h. The in vitro cytotoxicity assays demonstrated that GT/HA microneedles are not generally cytotoxic to chinese hamster ovary cells (CHO-K1), human embryonic kidney cells (293T), and mouse muscle cells (C2C12), which were treated for 12 and 24 h. Antimicrobial activity of the GT/HA microneedles was demonstrated by ~95% growth reduction of gram negative [Escherichia coli (E. coli), Pseudomonas putida (P. putida) and Salmonella typhimurium (S. typhimurium)] and gram positive bacteria [Staphylococcus aureus (S. Aureus) and Bacillus subtilis (B. subtilis)], with GT70. Furthermore, GT/HA microneedles reduced bacterial growth in the infected skin wound sites and improved skin wound healing process in rat model.

• 공업화학
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• 제35권3호
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• pp.192-199
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• 2024

본 연구에서 carbamazepine (CBZ) 각인 도토리 전분(acorn starch, AS)/PVA 기반 바이오소재를 casting method와 UV 조사를 이용하여 제조하고 물리·화학적 특성, CBZ 흡착 및 방출 특성을 조사하였다. 제조한 바이오소재의 표면 특성은 FE-SEM을 통해 확인하였고, UV 조사에 따른 CBZ의 안정성과 바이오소재 작용기는 FT-IR 분석을 이용하였다. CBZ에 대한 바이오소재의 흡착 특성은 binding isotherm 및 Scatchard plot으로 평가하였고 이를 통해 CBZ 각인 바이오소재에 CBZ 결합 부위가 존재하는 것을 확인하였다. 경피 약물 전달 시스템의 응용 가능성을 평가하기 위하여 36.5 ℃에서 다양한 pH의 완충용액과 인공피부를 이용해 제조한 바이오소재의 CBZ 방출 특성을 조사하였다. 이 결과, CBZ는 pH 가 증가할수록 빠른 방출 속도를 보였으며, 인공피부 테스트에서 12 h 동안 지속적으로 방출되었다. 또한, 수학적 모델을 적용시킨 결과, 완충용액에서 CBZ 방출 메커니즘은 pseudo-Fickian diffusion 메커니즘을 따랐고 인공피부에서 non-Fickian diffusion 메커니즘을 따르는 것으로 평가되었다.