• Journal of Pharmaceutical Investigation
• /
• v.29 no.3
• /
• pp.171-177
• /
• 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.

• Applied Chemistry for Engineering
• /
• v.32 no.5
• /
• pp.556-561
• /
• 2021

Recently, iron oxide nanoparticles have been used as the subject of many studies on drug delivery system (DDS) due to their excellent magnetic properties and biocompatibility in response to external magnetic fields. In this study, hyaluronic acid-superparamagnetic microneedles (HA-SMNs) and carboxy methyl cellulose-superparamagnetic microneedles (CMC-SMNs) containing superparamagnetic iron oxide nanoparticles (SIONs) were prepared with HA and CMC as a matrix materials of MNs (microneedles). Various properties of SMNs were then investigated with scanning electron microscopy (SEM), superconducting quantum interference device-vibrating sample magnetometer (SQUD-VSM), frequency mixing magnetic detection (FMMD), and polymer/bio membrane. The SQUID-VSM measurements showed superparamagnetism of HA-SMNs and CMC-SMNs containing SIONs. The FMMD results demonstrated that the signal intensity changed significantly as the concentration of SIONs increased. In addition, SMNs exhibited the average skin permeability intensities on the bio membrane for HA-SMNs and CMC-SMNs were 92.5 and 98.5%, respectively. These results suggested that SMNs could be utilized as deliver materials for a TDDS and MR molecular imaging.

• Transactions of the Korean Society of Mechanical Engineers A
• /
• v.28 no.12
• /
• pp.1871-1876
• /
• 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
• /
• v.25 no.1
• /
• pp.15-20
• /
• 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
• /
• v.32 no.4
• /
• pp.313-319
• /
• 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
• /
• v.46 no.2
• /
• pp.211-216
• /
• 2008

Bufexamac which was used for treatment of atopic dermatitis is the drug which was made as the ointment. However, penetration rate of bufexamac was very low for the barrier effect of stratum corneum. Microneedle was used to increase transdermal delivery rate of the bufexamac. We tried to conjugate bufexamac and FITC for the detection of penetration rate of bufexamac. FITC-bufexamac was mixed in hydrogel for the treatment skin surface. Fluorescent spectrophotometer was used to analysis the concentration of FITC-bufexamac. Microscope using fluorescent filter was used to capture the image about location of FITC-bufexamac in the skin. We confirmed that permeation rate of bufexamac was increased with the treatment by microneedle and was increased by the increasing number treatment of microneedle.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.5
• /
• pp.321-329
• /
• 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.

• Proceedings of the Korean Vacuum Society Conference
• /
• 2014.02a
• /
• pp.411.1-411.1
• /
• 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.

• Proceedings of the KSME Conference
• /
• 2007.05a
• /
• pp.1259-1264
• /
• 2007

Microstereolithography technology has potential capability for fabrication of 3D microstructures. It evolved from conventional SLA which is one of the RP processes. In a microstereolithography process, 3D microstructures can be easily fabricated by continuously stacking 2D layer which is photopolymerized using a liquid prepolymer. Combination between biocompatible/biodegradable photocurable prepolymer and 3D complex fabrication in microstereolithography makes broad application areas such as medical, pharmaceutic, and bio devices. In particular, a 3D microneedle for transdermal drug delivery and a scaffold for tissue engineering are fabricated using this technology. In this paper, the authors address development of microstereolithography system adapted to large surface and fabrication of various microstructures. In addition, to apply human body we suggest a biodegradable 3D microneedle and a scaffold using biodegradable photocurable prepolymer.

• Journal of Pharmaceutical Investigation
• /
• v.33 no.2
• /
• pp.79-84
• /
• 2003

The effects of various pressure sensitive adhesives (PSA) and enhancers on the percutaneous absorption of tulobuterol were investigated. The permeation rate of tulobuterol through hairless mouse skin from various adhesives was evaluated using a flow-through diffusion cell system at $37^{\circ}C$. The permeability of tulobuterol was variable depending on the physicochemical property of the PSA. The permeation rate of tulobuterol from polyethylene oxide grafted acrylic adhesive matrix was higher than that from other PSA matrices. The flux of tulobuterol was $4.37{\pm}0.34\;{\mu}g/hr/cm^2$ from polyethylene oxide grafted acrylic adhesive matrix. When the effects of various enhancers on the percutaneous absorption of tulobuterol from grafted acrylic adhesive were evaluated, Plurol $oleique^{\circledR}$ showed higher flux than all other enhancers tested.