마이크로니들의 형태 및 적용방법이 약물의 피부 투과에 미치는 영향

임지호,이경록,이은주,조정원 충남대학교 약학대학 의약품개발연구소 2012 藥學論文集 Vol.27 No.-

The purpose of this study is to develop the microneedle using biodegradable and biocompatible polymer and to pioneer the new route of drug delivery through the research to apply the most desirable administration form of small molecules, peptides, proteins, genes, biological products including vaccines. Various biocompatible microneedles were manufactured. To apply drug to microneedle, drug formulation using ethylene vinyl acetate patch or polyacryl acid gel was developed. Drug permeation into rat skin based on the application method of patch or gel with microneedle was studied using Franz diffusion cell system. In vitro drug permeation results showed that the permeation by the application of hollow microneedle was not increased compared with solid microneedle. When G60 or G60*2 microneedle was used, the permeated amount of calcein was increased compared to when solid microneedle was used. The permeated amount of lidocaine HCl in 12 hr was increased when microneedle was used was increased. Skin irritation followed by microneedle showed there was little difference in the decrease of redness after microneedle application based on application time.

Repeated Microneedle Stimulation Induces Enhanced Hair Growth in a Murine Model

( Yoon Seob Kim ),( Kwan Ho Jeong ),( Jung Eun Kim ),( Young Jun Woo ),( Beom Joon Kim ),( Hoon Kang ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.5

Background: Microneedle is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. No previous study showed a therapeutic effect of microneedle itself on hair growth by wounding. Objective: The aim of this study is to investigate the effect of repeated microwound formed by microneedle on hair growth and hair growth-related genes in a murine model. Methods: A disk microneedle roller was applied to each group of mice five times a week for three weeks. First, to identify the optimal length and cycle, microneedles of lengths of 0.15 mm, 0.25 mm, 0.5 mm, and 1 mm and cycles of 3, 6, 10, and 13 cycles were applied. Second, the effect of hair growth and hair-growth-related genes such as Wnt3a, β-catenin, vascular endothelial growth factor (VEGF), and Wnt10b was observed using optimized microneedle. Outcomes were observed using visual inspection, real-time polymerase chain reaction, and immunohistochemistry. Results: We found that the optimal length and cycle of microneedle treatment on hair growth was 0.25 mm/10 cycles and 0.5 mm/10 cycles. Repeated microneedle stimulation promoted hair growth, and it also induced the enhanced expression of Wnt3a, β-catenin, VEGF, and Wnt10b. Conclusion: Our study provides evidence that microneedle stimulation can induce hair growth via activation of the Wnt/β-catenin pathway and VEGF. Combined with the drug delivery effect, we believe that microneedle stimulation could lead to new approaches for alopecia. (Ann Dermatol 28(5) 586∼592, 2016)

Microneedle-Mediated Transdermal Delivery of Chondroitin Sulfate

( Yun Tae Kim ),( Sik Il Ahn ),( Hyun Jin Park ),( Su Hyun Jung ),( Hee Kyung Hong ),( Han Koo Lee ),( Dong Won Lee ),( John M Rhee ),( Kye Hwan Lee ),( Gil Son Khang ) 한국조직공학·재생의학회 2009 조직공학과 재생의학 Vol.6 No.4

Microneedle-mediated transdermal drug delivery is a non-invasive delivery method for drugs through the various layers of the skin to reach systemic circulation. Microneedles are large enough to permeate through skin and form microconduits that allow drugs to penetrate into skin, but small enough to avoid causing pain. In this study, we prepared a microneedle dermaroller composed of 3600 microneedles with 230 ?m in length and examined the effects of microneedle pretreatment on the skin permeation of chondroitin sulfate. t was confirmed that microneedles created microconduits that allow chondroitin sulfate to permeate into skin. The more microneedle treatment created more microconduits, leading to the more permeation of CS-FITC into skin. Microneedle treatment in mutual cross direction is more effective in CS-FITC-permeation than in parallel direction. After microneedle pretreatment, CSFITC exhibited a more permeationinto skin in the formulation of hydrogel than in solution. This work demonstrates the feasibilityof microneedle-mediated transdermal delivery of chondroitin sulfate.

Bioinspired microneedle insertion for deep and precise skin penetration with low force: Why the application of mechanophysical stimuli should be considered

Kim, Jonghun,Park, Sungmin,Nam, Gyungmok,Choi, Young,Woo, Seungpyo,Yoon, Sang-Hee Elsevier 2018 Journal of the mechanical behavior of biomedical m Vol.78 No.-

<P><B>Abstract</B></P> <P>A mosquito is known to precisely and easily insert its proboscis to the human skin by pressing down a labium and vibrating a fascicle bundle. Its advanced skin-piercing mechanisms indicate that skin resistance to the insertion of needle-like objects can be changed by the application of mechanophysical stimuli. Here, we characterize the effect of the application of mechanophysical stimuli on skin resistance to microneedle insertion to find clues for inserting a microneedle in a deep and precise fashion with low force. Microneedles with a diameter of 60–140µm are inserted at a velocity of 0.1–2.0mm/s to full-thickness porcine skins while either <I>uniaxial/equibiaxial stretch</I> of 0–20% or <I>mechanical vibration</I> at a frequency of 1 to 1000Hz and an amplitude of 1–10µm is applied to the skins as static or dynamic mechanophysical stimulus, respectively. The values of force and depth at two events of skin puncture and maximum penetration are measured to explore changes in skin resistance induced by the application of external stimuli. The static mechanophysical stimulus applied to the skin mainly affects the precision of microneedle insertion; the application of dynamic mechanophysical stimulus controls the value and deviation of skin resistance to microneedle insertion. The application of mechanophysical stimuli, inspired from a mosquito, therefore allows a microneedle to be deeply and easily inserted to the skin in a controlled way. The findings will have broad impacts on microneedle-mediated applications and lead to an in-depth understanding of skin biomechanics.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Mechanophysical stimuli are applied to the skin during microneedle insertion. </LI> <LI> Stretch and mechanical vibration are considered as mechanophysical stimuli. </LI> <LI> Changes in skin resistance caused by the application of stimuli are investigated. </LI> <LI> The method allows deep, easy microneedle insertion to the skin in a controlled way. </LI> <LI> This study elucidates the biological mechanisms used by mosquito and honey bee. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Repeated microneedle stimulation induces enhanced hair growth through the Wnt/β-catenin pathway in a murine model

( Yoon Seob Kim ),( Kwan Ho Jeong ),( Young Jun Woo ),( Hong Jin Joo ),( Jung Eun Kim ),( Beom Joon Kim ),( Hoon Kang ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Microneedle treatment is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. Wound-induced hair follicle regeneration via the Wnt/モ-catenin signaling pathway following wounding in adult mice was demonstrated. No previous study showed a therapeutic effect of microneedle on hair growth by wounding. Objectives: We aimed to investigate the effect of repeated microwound formed by microneedle treatment on hair growth and hair-growth-related genes in a murine model. Methods: A disk-type microneedle roller was applied to each group of mice five times a week for three weeks. First, to identify the optimal length and cycle, microneedles of lengths of 0.15, 0.25, 0.5, and 1 mm and cycles of 3, 6, 10, and 13 cycles were applied. Second, the effect of hair growth and hair-growth-related genes such as Wnt3a, モ-catenin, VEGF, and Wnt10b was observed using optimized microneedle. Outcomes were observedusing visual inspection, real-time polymerase chain reaction, and immunohistochemistry. Results: We found that the optimal length and cycle of microneedle treatment on hair growth was 0.25 mm/10 cycle and 0.5mm/10 cycle. Repeated microneedle stimulation promoted hair growth, and it also induced the enhanced expression of Wnt3a, モ-catenin, VEGF, and Wnt10b. Conclusion: Our study provides evidence that microneedle stimulation can induce hair growth via activation of a wound healing process that includes the Wnt/モ-catenin pathway and VEGF.

Analysis of the Mechanical Failure of Polymer Microneedles by Axial Force

박정환,Mark R. Prausnitz 한국물리학회 2010 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.56 No.4

A polymeric microneedle has been developed for drug delivery applications. The ultimate goal of the polymeric microneedle is insertion into the specified region without failure for effective transdermal drug delivery. The mechanical failure of various geometries of microneedles by axial load was modeled using the Euler formula and the Johnson formula to predict the failure force of taperedcolumn microneedles. These formulas were compared with measured data to identify the mechanical behavior of microneedles by determining the critical factors, including the actual length and the end-fixed factor. The comparison of the two formulas with the data showed good agreement at an end-fixity (K) of 0.7. This value means that a microneedle column has one fixed end and one pinned end and that part of the microneedle is overloaded by an axial load. When the aspect ratio of length-to-equivalent diameter is 12:1 at Young’s modulus of 3 GPa, there is a transition from the Euler region to the Johnson region due to the decreased length and the increased base diameter of the microneedle. A polymer having a stiffness of less than 3 GPa would follow the Euler formula. A 12:1 aspect ratio of length-to-equivalent diameter of the microneedle is a mechanical indicator determining the failure mode between elastic buckling and inelastic buckling at Young’s modulus of less than 3 GPa for polymer. Microneedles with an aspect ratio of length-to-equivalent diameter below 12:1 and Young’s modulus of more than 3 GPa are recommended for reducing sudden failure by buckling and for successfully inserting a microneedle into the skin.

Bio-inspired Protein & Polymer Networked Mechanically Reinforced Adhesive Microneedle Platform for Improved Transdermal Drug Delivery

Hyeok Jun LEE,Seong-Woo MAENG,Hyung Joon CHA 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Previously, mussel adhesive protein (MAP)-based microneedle platform has been developed, which is the minimal invasive method, and it allows to attach to biological tissues by virtue of superior adhesive property. Using this platform, it was possible to heal vascular/gastrointestinal wounds or to deliver drug transdermally to target tissues. However, the previously developed MAP-based microneedle was difficult to use for highly motile or tough tissues, such as the heart due to its low mechanical strength. To overcome this shortcoming, double-layered structure to polyethylene glycol (PEG)-MAP network was utilized in this research, with a higher mechanical strength than the previous microneedle. In addition, through lysine cross-linking, more adhesive microneedle was achieved. Through sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), it was possible to check the bond of the MAP-PEG macromolecule, which indicated high molecular weight. The MAP-PEG microneedle patch was formed evenly compared to the previous microneedle patch. Moreover, the mechanical strength was measured through the tissue insertion test, and it was confirmed that it was more than twice as high as the previous microneedle. Finally, it was found that cytotoxicity of MAP-PEG microneedle was very low through confirming 95% or more cells in the live state.

Therapeutic Effects of Growth Factor Cocktail Treatment in Patients with Androgenetic Alopecia According to the Depth of Microneedle

( Byung In Ro ),( Hyun Ok Son ),( Sin Wook Chun ),( Hang Cheol Shin ) 대한피부과학회 2016 大韓皮膚科學會誌 Vol.54 No.3

Background: Growth factor treatment in combination with microneedling in androgenetic alopecia (AGA) patients is safe and effective. However, there is a lack of studies examining the effect of treatment according to the depth of the microneedle. Objective: The aim was to evaluate differences in efficacy according to the depth of microneedle. Methods: This study was performed on 6 male and 5 female AGA patients who were treated with topical growth factor cocktail (GFC) with microneedling every 2 weeks for 3 months. The scalp was divided into right and left sides and treated with microneedle depths of 0.5 and 0.3 mm, respectively. GFC was topically applied using a microneedle medical device. Treatment efficacy was evaluated by phototrichogram and digital photograph analysis on 6 repeated treatments for 3 months. Results: Phototrichogram of the 0.5- and 0.3-mm-treated sides of the scalp showed 19 and 12 cm2 increase in hair density and 2.6- and 1.8-μm increase in hair diameter, respectively. These results were statistically significant (p< 0.05). In terms of density, the 0.5-mm depth was significantly more effective than the 0.3-mm depth (p<0.05). With regard to diameter, the effect according to microneedle depth was not significantly different (p>0.05). Conclusion: GFC treatment with microneedling is effective and safe and a microneedle depth of 0.5 mm appears to be more effective than that of 0.3 mm. More research is necessary to confirm these results and determine the most effective depth for microneedling by investigating various depths. (Korean J Dermatol 2016;54(3):184~189)

초음파 결합 마이크로니들 시스템을 통한 진정 및 재생 활성성분 경피전달

우재현,곽나영 한국화장품미용학회 2023 한국화장품미용학회지 Vol.13 No.1

The beauty treatment industry has been growing worldwide since the 2000s. However, despite this progress, research and post-treatment care for the pain and side effects caused by beauty care treatments have been lagging behind. This study proposes a new device that combines the advantages of the Dissolving Microneedle Channeling System and ultrasonic treatment. Dissolving Microneedle Channeling System and ultrasonic treatment have been developed to overcome the drawbacks of conventional treatments such as laser skin resurfacing and Microneedling Therapy Systems (MTS). To address the disadvantages of Dissolving Microneedle Channeling System and ultrasonic treatment, a Sucralfate 0.5% and Vitamin K 3% solution is applied to the Dissolving Microneedle Channeling System, which is known as KS-DMCS, to facilitate wound healing caused by the microneedles. Additionally, an external serum (Ceutisome Serum) containing liquid oxygen cosmetics is used to activate skin cells. Experimental results confirm that the combination of ultrasonic treatment and Dissolving Microneedle Channeling System demonstrates significant improvement. The feasibility test confirms the stability of the Sucralfate 0.5% and Vitamin K 3% solution with the needle array. It is also confirmed that the serum, which contains liquid oxygen cosmetics, diffuses to the target depth without interference from the Sucralfate 0.5% and Vitamin K 3% solution. Therefore, the combination of ultrasonic treatment and Dissolving Microneedle Channeling System exhibits a better delivery effect compared to using Dissolving Microneedle Channeling System or ultrasonic treatment alone, successfully delivering each active ingredient to the desired depth. This study proposes this combination as an innovative strategy for a system that enhances the efficacy of skincare and facilitates the delivery of active ingredients without causing pain or side effects to the user. 미용치료 산업은 2000년대부터 전 세계적으로 성장해 왔다. 그러나 이러한 발전에도 불구하고 미용 시술로 인한 통증과 부작용에 대한 연구와 사후 관리는 뒤쳐져 왔다. 본 연구는 용해 마이크로니들 채널링 시스템과 초음파 처리의 장점을 결합한 새로운 장치를 제안하는데 그 목적이 있다. 레이저 피부미용 시술(Skin LASER) 및 마이크로니들링 테라피 시스템(MTS)과 같은 기존 치료법의 단점을 극복하기 위해 용해 마이크로니들링 시스템과 초음파 치료법이 개발되었다. KS-DMCS로 알려진 용해성 마이크로니들 채널링 시스템에는 용해성 마이크로니들 채널링 시스템과 초음파 처리의 단점을 해결하기 위해 수크랄페이트 0.5%와 비타민 K 3% 용액을 적용하여 마이크로니들에 의한 상처 치유를 용이하게 한다. 또한, 액체 산소 화장품이 함유된 외부 세럼(Ceutisome Serum)을 사용하여 피부 세포를 활성화한다. 실험 결과 초음파 처리와 용해 마이크로니들 채널링 시스템의 조합이 상당한 개선을 나타냄을 확인하였으며, 타당성 테스트를 통해 마이크로 니들과 Sucralfate 0.5% 및 Vitamin K 3% 혼합 용액과 서로 반응치 않는 안정성을 확인하였다. 또한 액체산소가 함유된 세럼이 Sucralfate 0.5% 및 Vitamin K 3% 혼합 용액과 간섭 반응성 없이 목표 깊이까지 확산되는 것을 확인할 수 있었다. 따라서 초음파 처리와 용해 마이크로니들 채널링 시스템의 조합은 용해 마이크로니들 채널링 시스템을 단독으로 사용하거나 초음파 처리를 단독으로 사용하는 경우보다 더 나은 경피전달 효과를 보이며, 각 활성 성분을 원하는 깊이까지 성공적으로 전달할 수 있다. 본 연구에서는 이러한 조합을 사용자에게 통증이나 부작용을 주지 않으면서 스킨케어의 효능을 높이고 유효성분의 전달을 용이하게 하는 시스템을 위한 혁신적인 전략으로 제안하고자 한다.

초기변형률에 의한 피부조직의 미소바늘관통저항 감소에 관한 연구

김종훈(Jonghun Kim),박성민(Sungmin Park),김도훈(Dohoon Kim),남경목(Gyung Mok Nam),윤상희(Sang-Hee Yoon) 대한기계학회 2015 대한기계학회 춘추학술대회 Vol.2015 No.11

Despite all the recent advances made in the biodegradable microneedle field, the mechanical failure of a microneedle during insertion remains a major technical hurdle in the path of large scale commercialization. A controllable reduction in the microneedle puncture resistance of skin tissues is therefore an essential requirement for developing a biodegradable microneedle. Here, we consider unidirectional or multidirectional prestress on skin tissues as a critical stimulus to reducing the microneedle puncture resistance, and investigate the effect of prestress on the changes in microneedle insertion behavior (e.g., puncture resistance, insertion force, etc.) in a quantitative way. For pork skin tissues similar to human ones, microneedle insertion behavior is characterized with a z-axis motorized stage equipped with a load cell, together with microindenters; the experimental apparatus provides a force-time curve which contains information on microneedle puncture and insertion into skin tissues. The experimental results lead to quantifying the relation between microneedle insertion behavior and prestrain. The findings of this study will lead to better understanding of skin tissue biomechanics.