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Sample records for hollow microneedles permitted

  1. Method to fabricate hollow microneedle arrays

    Energy Technology Data Exchange (ETDEWEB)

    Kravitz, Stanley H [Placitas, NM; Ingersoll, David [Albuquerque, NM; Schmidt, Carrie [Los Lunas, NM; Flemming, Jeb [Albuquerque, NM

    2006-11-07

    An inexpensive and rapid method for fabricating arrays of hollow microneedles uses a photoetchable glass. Furthermore, the glass hollow microneedle array can be used to form a negative mold for replicating microneedles in biocompatible polymers or metals. These microneedle arrays can be used to extract fluids from plants or animals. Glucose transport through these hollow microneedles arrays has been found to be orders of magnitude more rapid than natural diffusion.

  2. Sharp tipped plastic hollow microneedle array by microinjection moulding

    Science.gov (United States)

    Yung, K. L.; Xu, Yan; Kang, Chunlei; Liu, H.; Tam, K. F.; Ko, S. M.; Kwan, F. Y.; Lee, Thomas M. H.

    2012-01-01

    A method of producing sharp tipped plastic hollow microneedle arrays using microinjection moulding is presented in this paper. Unlike traditional approaches, three mould inserts were used to create the sharp tips of the microneedles. Mould inserts with low surface roughness were fabricated using a picosecond laser machine. Sharp tipped plastic hollow microneedles 500 µm in height were fabricated using a microinjection moulding machine developed by the authors’ group. In addition, the strength of the microneedle was studied by simulation and penetration experiments. Results show that the microneedles can penetrate into skin, delivering liquid successfully without any breakage or severe deformation. Techniques presented in this paper can be used to fabricate sharp tipped plastic hollow microneedle arrays massively with low cost.

  3. Sharp tipped plastic hollow microneedle array by microinjection moulding

    International Nuclear Information System (INIS)

    Yung, K L; Xu, Yan; Kang, Chunlei; Liu, H; Tam, K F; Ko, S M; Kwan, F Y; Lee, Thomas M H

    2012-01-01

    A method of producing sharp tipped plastic hollow microneedle arrays using microinjection moulding is presented in this paper. Unlike traditional approaches, three mould inserts were used to create the sharp tips of the microneedles. Mould inserts with low surface roughness were fabricated using a picosecond laser machine. Sharp tipped plastic hollow microneedles 500 µm in height were fabricated using a microinjection moulding machine developed by the authors’ group. In addition, the strength of the microneedle was studied by simulation and penetration experiments. Results show that the microneedles can penetrate into skin, delivering liquid successfully without any breakage or severe deformation. Techniques presented in this paper can be used to fabricate sharp tipped plastic hollow microneedle arrays massively with low cost. (paper)

  4. Microfabricated hollow microneedle array using ICP etcher

    Science.gov (United States)

    Ji, Jing; Tay, Francis E. H.; Miao, Jianmin

    2006-04-01

    This paper presents a developed process for fabrication of hollow silicon microneedle arrays. The inner hollow hole and the fluidic reservoir are fabricated in deep reactive ion etching. The profile of outside needles is achieved by the developed fabrication process, which combined isotropic etching and anisotropic etching with inductively coupled plasma (ICP) etcher. Using the combination of SF6/O2 isotropic etching chemistry and Bosch process, the high aspect ratio 3D and high density microneedle arrays are fabricated. The generated needle external geometry can be controlled by etching variables in the isotropic and anisotropic cases.

  5. Microfabricated hollow microneedle array using ICP etcher

    International Nuclear Information System (INIS)

    Ji Jing; Tay, Francis E H; Miao Jianmin

    2006-01-01

    This paper presents a developed process for fabrication of hollow silicon microneedle arrays. The inner hollow hole and the fluidic reservoir are fabricated in deep reactive ion etching. The profile of outside needles is achieved by the developed fabrication process, which combined isotropic etching and anisotropic etching with inductively coupled plasma (ICP) etcher. Using the combination of SF 6 /O 2 isotropic etching chemistry and Bosch process, the high aspect ratio 3D and high density microneedle arrays are fabricated. The generated needle external geometry can be controlled by etching variables in the isotropic and anisotropic cases

  6. Microfabricated hollow microneedle array using ICP etcher

    Energy Technology Data Exchange (ETDEWEB)

    Ji Jing [Mechanical Engineering National University of Singapore, 119260, Singapore (Singapore); Tay, Francis E H [Mechanical Engineering National University of Singapore, 119260, Singapore (Singapore); Miao Jianmin [MicroMachines Center, School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798 (Singapore)

    2006-04-01

    This paper presents a developed process for fabrication of hollow silicon microneedle arrays. The inner hollow hole and the fluidic reservoir are fabricated in deep reactive ion etching. The profile of outside needles is achieved by the developed fabrication process, which combined isotropic etching and anisotropic etching with inductively coupled plasma (ICP) etcher. Using the combination of SF{sub 6}/O{sub 2} isotropic etching chemistry and Bosch process, the high aspect ratio 3D and high density microneedle arrays are fabricated. The generated needle external geometry can be controlled by etching variables in the isotropic and anisotropic cases.

  7. Hydrodynamic gene delivery in human skin using a hollow microneedle device.

    Science.gov (United States)

    Dul, M; Stefanidou, M; Porta, P; Serve, J; O'Mahony, C; Malissen, B; Henri, S; Levin, Y; Kochba, E; Wong, F S; Dayan, C; Coulman, S A; Birchall, J C

    2017-11-10

    Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. An optimized hollow microneedle for minimally invasive blood extraction.

    Science.gov (United States)

    Li, Cheng Guo; Lee, Chang Yeol; Lee, Kwang; Jung, Hyungil

    2013-02-01

    The healthcare system relies widely on biochemical information obtained from blood sample extracted via hypodermic needles, despite the invasiveness and pain associated with this procedure. Therefore, an alternative micro-scale needle for minimally invasive blood sampling is highly desirable. Traditional fabrication techniques to create microneedles do not generate needles with the combined features of a sharp tip, long length, and hollow structure concurrently. Here, we report the fabrication of a microneedle long enough to reach blood vessels and sharp enough to minimize nerve contact for minimally invasive blood extraction. The microneedle structure was precisely controlled using a drawing lithography technique, and a sharp tip angle was introduced using a laser-cutting system. We investigated the characteristics of a microneedle with a length of 1,800 μm length, an inner diameter of 60 μm, a tip diameter of 120 μm, and a 15° bevel angle through in-vitro liquid extraction and mechanical strength analysis. We demonstrated that the proposed structure results in blood extraction at a reasonable rate, and that a microneedle with this geometry can reliably penetrate skin without breaking. We integrated this microneedle into a blood extraction device to extract a 20 μl volume of mouse blood in-vivo. Our optimized, hollow microneedle can potentially be incorporated with other cutting-edge technologies such as microactuators, biosensors, and microfluidic chips to create blood analysis systems for point-of-care diagnostics.

  9. Fabricating process of hollow out-of-plane Ni microneedle arrays and properties of the integrated microfluidic device

    Science.gov (United States)

    Zhu, Jun; Cao, Ying; Wang, Hong; Li, Yigui; Chen, Xiang; Chen, Di

    2013-07-01

    Although microfluidic devices that integrate microfluidic chips with hollow out-of-plane microneedle arrays have many advantages in transdermal drug delivery applications, difficulties exist in their fabrication due to the special three-dimensional structures of hollow out-of-plane microneedles. A new, cost-effective process for the fabrication of a hollow out-of-plane Ni microneedle array is presented. The integration of PDMS microchips with the Ni hollow microneedle array and the properties of microfluidic devices are also presented. The integrated microfluidic devices provide a new approach for transdermal drug delivery.

  10. Silicon micromachined hollow microneedles for transdermal liquid transport

    NARCIS (Netherlands)

    Gardeniers, Johannes G.E.; Lüttge, Regina; Berenschot, Johan W.; de Boer, Meint J.; Yeshurun, Shuki Y.; Hefetz, Meir; van 't Oever, Ronny; van den Berg, Albert

    2003-01-01

    This paper presents a novel process for the fabrication of out-of-plane hollow microneedles in silicon. The fabrication method consists of a sequence of deep-reactive ion etching (DRIE), anisotropic wet etching and conformal thin film deposition, and allows needle shapes with different,

  11. A repeatable and scalable fabrication method for sharp, hollow silicon microneedles

    Science.gov (United States)

    Kim, H.; Theogarajan, L. S.; Pennathur, S.

    2018-03-01

    Scalability and manufacturability are impeding the mass commercialization of microneedles in the medical field. Specifically, microneedle geometries need to be sharp, beveled, and completely controllable, difficult to achieve with microelectromechanical fabrication techniques. In this work, we performed a parametric study using silicon etch chemistries to optimize the fabrication of scalable and manufacturable beveled silicon hollow microneedles. We theoretically verified our parametric results with diffusion reaction equations and created a design guideline for a various set of miconeedles (80-160 µm needle base width, 100-1000 µm pitch, 40-50 µm inner bore diameter, and 150-350 µm height) to show the repeatability, scalability, and manufacturability of our process. As a result, hollow silicon microneedles with any dimensions can be fabricated with less than 2% non-uniformity across a wafer and 5% deviation between different processes. The key to achieving such high uniformity and consistency is a non-agitated HF-HNO3 bath, silicon nitride masks, and surrounding silicon filler materials with well-defined dimensions. Our proposed method is non-labor intensive, well defined by theory, and straightforward for wafer scale mass production, opening doors to a plethora of potential medical and biosensing applications.

  12. A hollow stainless steel microneedle array to deliver insulin to a diabetic rat

    International Nuclear Information System (INIS)

    Vinayakumar, K B; Rajanna, K; Kulkarni, Prachit G; Ramachandra, S G; Nayak, M M; Hegde, Gopalkrishna M; Dinesh, N S

    2016-01-01

    A novel fabrication process has been described for the development of a hollow stainless steel microneedle array using femto second laser micromachining. Using this method, a complicated microstructure can be fabricated in a single process step without using masks. The mechanical stability of the fabricated microneedle array was measured for axial and transverse loading. Skin histology was carried out to study the microneedle penetration into the rat skin. Fluid flow through the microneedle array was studied for different inlet pressures. The packaging of the microneedle array, to protect the microneedle bore blockage from dust and other atmospheric contaminations, was also considered. Finally, the microneedle array was tested and studied in vivo for insulin delivery to a diabetic rat. The results obtained were compared with the standard subcutaneous delivery with the same dose rate and were found to be in good agreement. (paper)

  13. A hollow stainless steel microneedle array to deliver insulin to a diabetic rat

    Science.gov (United States)

    Vinayakumar, K. B.; Kulkarni, Prachit G.; Nayak, M. M.; Dinesh, N. S.; Hegde, Gopalkrishna M.; Ramachandra, S. G.; Rajanna, K.

    2016-06-01

    A novel fabrication process has been described for the development of a hollow stainless steel microneedle array using femto second laser micromachining. Using this method, a complicated microstructure can be fabricated in a single process step without using masks. The mechanical stability of the fabricated microneedle array was measured for axial and transverse loading. Skin histology was carried out to study the microneedle penetration into the rat skin. Fluid flow through the microneedle array was studied for different inlet pressures. The packaging of the microneedle array, to protect the microneedle bore blockage from dust and other atmospheric contaminations, was also considered. Finally, the microneedle array was tested and studied in vivo for insulin delivery to a diabetic rat. The results obtained were compared with the standard subcutaneous delivery with the same dose rate and were found to be in good agreement.

  14. Sharpening of hollow silicon microneedles to reduce skin penetration force

    International Nuclear Information System (INIS)

    Khanna, Puneet; Luongo, Kevin; Bhansali, Shekhar; Strom, Joel A

    2010-01-01

    In this research, hollow silicon microneedles with sharpened tips have been fabricated without any reduction to the needle shaft diameter. By sharpening the needles only at the tip and not over the entire length of the needle, their mechanical strength is maintained, while reducing the insertion force into skin. The process achieves this geometry by novel use photoresist depletion during DRIE. Microneedles of varying levels of tip sharpness were tested on human cadaver skin to measure their force of penetration. The results show a marked decrease of insertion force with progressive sharpening of microneedle tips, reducing more than 75 times in magnitude for extremely sharp tips. The toughness of human skin was derived to be approximately 24.28 kJ m −2 .

  15. Fabrication process for tall, sharp, hollow, high aspect ratio polymer microneedles on a platform

    International Nuclear Information System (INIS)

    Ceyssens, Frederik; Chaudhri, Buddhadev Paul; Van Hoof, Chris; Puers, Robert

    2013-01-01

    This paper reports on a new lithographic process for fabricating arrays of tall, high aspect ratio (defined as height/wall thickness), hollow, polymer microneedles on a platform. The microneedles feature a high sharpness (down to 3 µm tip radius) and aspect ratio (>65) which is a factor 2 and 4 better than the state of the art, respectively. The maximum achievable needle shaft length is over 1 mm. The improved performance was obtained by using an anisotropically patterned silicon substrate covered with an antireflective layer as mold for the needle tip and an optimized SU-8 lithographic process. Furthermore, a platform containing liquid feedthroughs holding an arbitrary number of needles out of plane can be manufactured with only one additional process step. The high aspect ratio microneedles undergo failure at the critical load of around 230 mN in the case of 1 mm long hollow needles with triangular cross section and a base of 175 µm. Penetration into human skin is demonstrated as well. (paper)

  16. Hollow silicon microneedle array based trans-epidermal antiemetic patch for efficient management of chemotherapy induced nausea and vomiting

    Science.gov (United States)

    Kharbikar, Bhushan N.; Kumar S., Harish; Kr., Sindhu; Srivastava, Rohit

    2015-12-01

    Chemotherapy Induced Nausea and Vomiting (CINV) is a serious health concern in the treatment of cancer patients. Conventional routes for administering anti-emetics (i.e. oral and parenteral) have several drawbacks such as painful injections, poor patient compliance, dependence on skilled personnel, non-affordability to majority of population (parenteral), lack of programmability and suboptimal bioavailability (oral). Hence, we have developed a trans-epidermal antiemetic drug delivery patch using out-of-plane hollow silicon microneedle array. Microneedles are pointed micron-scale structures that pierce the epidermal layer of skin to reach dermal blood vessels and can directly release the drug in their vicinity. They are painless by virtue of avoiding significant contact with dermal sensory nerve endings. This alternate approach gives same pharmacodynamic effects as par- enteral route at a sparse drug-dose requirement, hence negligible side-effects and improved patient compliance. Microneedle design attributes were derived by systematic study of human skin anatomy, natural micron-size structures like wasp-sting and cactus-spine and multi-physics simulations. We used deep reactive ion etching with Bosch process and optimized recipe of gases to fabricate high-aspect-ratio hollow silicon microneedle array. Finally, microneedle array and polydimethylsiloxane drug reservoir were assembled to make finished anti-emetic patch. We assessed microneedles mechanical stability, physico-chemical properties and performed in-vitro, ex- vivo and in-vivo studies. These studies established functional efficacy of the device in trans-epidermal delivery of anti-emetics, its programmability, ease of use and biosafety. Thus, out-of-plane hollow silicon microneedle array trans-epidermal antiemetic patch is a promising strategy for painless and effective management of CINV at low cost in mainstream healthcare.

  17. In Vivo Experimental Study of Noninvasive Insulin Microinjection through Hollow Si Microneedle Array

    Directory of Open Access Journals (Sweden)

    Drago Resnik

    2018-01-01

    Full Text Available An experimental study of in vivo insulin delivery through microinjection by using hollow silicon microneedle array is presented. A case study was carried out on a healthy human subject in vivo to determine the influence of delivery parameters on drug transfer efficiency. As a microinjection device, a hollow microneedle array (13 × 13 mm2 having 100 microneedles (220 µm high, 130 µm-outer diameter and 50 µm-inner diameter was designed and fabricated using classical microfabrication techniques. The efficiency of the delivery process was first characterized using methylene blue and a saline solution. Based on these results, the transfer efficiency was found to be predominantly limited by the inability of viable epidermis to absorb and allow higher drug transport toward the capillary-rich region. Two types of fast-acting insulin were used to provide evidence of efficient delivery by hollow MNA to a human subject. By performing blood analyses, infusion of more-concentrated insulin (200 IU/mL, international units (IU exhibited similar blood glucose level drop (5–7% compared to insulin of standard concentration (100 IU/mL, however, significant increase of serum insulin (40–50% with respect to the preinfusion values was determined. This was additionally confirmed by a distinctive increase of insulin to C-peptide ratio as compared to preinfusion ratio. Moreover, we noticed that this route of administration mimics a multiple dose regimen, able to get a “steady state” for insulin plasma concentration.

  18. Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes

    Science.gov (United States)

    Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Dübner, Matthias; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

    2016-07-01

    Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50-100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering.

  19. Design considerations of a hollow microneedle-optofluidic biosensing platform incorporating enzyme-linked assays

    Science.gov (United States)

    Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

    2018-02-01

    A hollow metallic microneedle is integrated with microfluidics and photonic components to form a microneedle-optofluidic biosensor suitable for therapeutic drug monitoring (TDM) in biological fluids, like interstitial fluid, that can be collected in a painless and minimally-invasive manner. The microneedle inner lumen surface is bio-functionalized to trap and bind target analytes on-site in a sample volume as small as 0.6 nl, and houses an enzyme-linked assay on its 0.06 mm2 wall. The optofluidic components are designed to rapidly quantify target analytes present in the sample and collected in the microneedle using a simple and sensitive absorbance scheme. This contribution describes how the biosensor components were optimized to detect in vitro streptavidin-horseradish peroxidase (Sav-HRP) as a model analyte over a large detection range (0-7.21 µM) and a very low limit of detection (60.2 nM). This biosensor utilizes the lowest analyte volume reported for TDM with microneedle technology, and presents significant avenues to improve current TDM methods for patients, by potentially eliminating blood draws for several drug candidates.

  20. Enhanced immunity in intradermal vaccination by novel hollow microneedles.

    Science.gov (United States)

    Ogai, N; Nonaka, I; Toda, Y; Ono, T; Minegishi, S; Inou, A; Hachiya, M; Fukamizu, H

    2018-04-29

    The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. A combined approach of hollow microneedles and nanocarriers for skin immunization with plasmid DNA encoding ovalbumin

    Directory of Open Access Journals (Sweden)

    Pamornpathomkul B

    2017-01-01

    Full Text Available Boonnada Pamornpathomkul,1 Adisak Wongkajornsilp,2 Wanida Laiwattanapaisal,3 Theerasak Rojanarata,1 Praneet Opanasopit,1 Tanasait Ngawhirunpat1 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Pharmaceutical Development of Green Innovations Group, Silpakorn University, Nakhon Pathom, 2Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 3Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand Abstract: The aim of this study was to investigate the use of different types of microneedles (MNs and nanocarriers for in vitro skin permeation and in vivo immunization of plasmid DNA encoding ovalbumin (pOVA. In vitro skin permeation studies indicated that hollow MNs had a superior enhancing effect on skin permeation compared with solid MN patches, electroporation (EP patches, the combination of MN and EP patches, and untreated skin. Upon using hollow MNs combined with nanocarriers for pOVA delivery, the skin permeation was higher than for the delivery of naked pOVA, as evidenced by the increased amount of pOVA in Franz diffusion cells and immunoglobulin G (IgG antibody responses. When the hollow MNs were used for the delivery of nanocarrier:pOVA complexes into the skin of mice, they induced a stronger IgG immune response than conventional subcutaneous (SC injections. In addition, immunization of mice with the hollow MNs did not induce signs of skin infection or pinpoint bleeding. Accordingly, the hollow MNs combined with a nanocarrier delivery system is a promising approach for delivering pOVA complexes to the skin for promoting successful immunization. Keywords: hollow microneedle, solid microneedle, electroporation, plasmid DNA encoding ovalbumin, skin immunization, nanocarrier

  2. Tissue expansion and fluid absorption by skin tissue following intradermal injections through hollow microneedles

    Science.gov (United States)

    Shrestha, Pranav; Stoeber, Boris

    2017-11-01

    Hollow microneedles provide a promising alternative to conventional drug delivery techniques due to improved patient compliance and the dose sparing effect. The dynamics of fluid injected through hollow microneedles into skin, which is a heterogeneous and deformable porous medium, have not been investigated extensively in the past. We have introduced the use of Optical Coherence Tomography (OCT) for real-time visualization of fluid injections into excised porcine tissue. The results from ex-vivo experiments, including cross-sectional tissue images from OCT and pressure/flow-rate measurements, show a transient mode of high flow-rate into the tissue followed by a lower steady-state infusion rate. The injected fluid expands the underlying tissue and causes the external free surface of the skin to rise, forming a characteristic intradermal wheal. We have used OCT to visualize the evolution of tissue and free surface deformation, and advancement of the boundary between regions of expanding and stationary tissue. We will show the effect of different injection parameters such as fluid pressure, viscosity and microneedle retraction on the injected volume. This work has been supported through funding from the Collaborative Health Research Program by the Natural Science and Engineering Research Council of Canada and the Canadian Health Research Institute, and through the Canada Research Chairs program.

  3. Administration of a Sol-Gel Formulation of Phenylephrine Using Low-Temperature Hollow Microneedle for Treatment of Intermittent Fecal Incontinence.

    Science.gov (United States)

    Lee, Hyunji; Park, Jung-Hwan; Park, Jung Ho

    2017-12-01

    A low temperature hollow microneedle system was devised to deliver sol-gel transition formulation near the surface of the skin for extended release and local delivery of drug by a non-invasive method. This new system can improve treatment of intermittent fecal incontinence. The low-temperature system was integrated with a hollow microneedle to maintain the low temperature of the sol formulation. Various sol-gel formulations using Pluronic F-127 (PF-127) and Hydroxy-propyl-methyl-cellulose (HPMC) were prepared, and their gelation temperature, flow property, and diffusion retardation were observed. Resting anal sphincter pressure in response to a phenylephrine (PE) sol-gel formulation was measured using an air-charged catheter. The biocompatibility of the sol-gel PE formulation was evaluated by observing the immunological response. When the PF-127 25%, HPMC 1% and PE formulation (PF25-HPMC1-PE) was injected through the peri-anal skin of the rat in vivo, the highest pressure on the anal sphincter muscle occurred at 6-8 h and anal pressure increased and lasted twice as long as with the phosphate-buffered saline (PBS)-PE formulation. There was no significant difference in the number of mast cells after administration into the rat in vivo between the PF25-HPMC1-PE formulation and the PBS-PE formulation. The combination of a low-pain hollow microneedle system and an injectable sol-gel formulation improved the efficacy of treatment of intermittent fecal incontinence. A low-temperature hollow microneedle system using a sol-gel formulation has many applications in medical treatments that require depot effect, local targeting, and pain control.

  4. Silica needle template fabrication of metal hollow microneedle arrays

    International Nuclear Information System (INIS)

    Zhu, M W; Li, H W; Chen, X L; Tang, Y F; Lu, M H; Chen, Y F

    2009-01-01

    Drug delivery through hollow microneedle (HMN) arrays has now been recognized as one of the most promising techniques because it minimizes the shortcomings of the traditional drug delivery methods and has many exciting advantages—pain free and tunable release rates, for example. However, this drug delivery method has been hindered greatly from mass clinical application because of the high fabrication cost of HMN arrays. Hence, we developed a simple and cost-effective procedure using silica needles as templates to massively fabricate HMN arrays by using popular materials and industrially applicable processes of micro- imprint, hot embossing, electroplating and polishing. Metal HMN arrays with high quality are prepared with great flexibility with tunable parameters of area, length of needle, size of hollow and array dimension. This efficient and cost-effective fabrication method can also be applied to other applications after minor alterations, such as preparation of optic, acoustic and solar harvesting materials and devices

  5. Silica needle template fabrication of metal hollow microneedle arrays

    Science.gov (United States)

    Zhu, M. W.; Li, H. W.; Chen, X. L.; Tang, Y. F.; Lu, M. H.; Chen, Y. F.

    2009-11-01

    Drug delivery through hollow microneedle (HMN) arrays has now been recognized as one of the most promising techniques because it minimizes the shortcomings of the traditional drug delivery methods and has many exciting advantages—pain free and tunable release rates, for example. However, this drug delivery method has been hindered greatly from mass clinical application because of the high fabrication cost of HMN arrays. Hence, we developed a simple and cost-effective procedure using silica needles as templates to massively fabricate HMN arrays by using popular materials and industrially applicable processes of micro- imprint, hot embossing, electroplating and polishing. Metal HMN arrays with high quality are prepared with great flexibility with tunable parameters of area, length of needle, size of hollow and array dimension. This efficient and cost-effective fabrication method can also be applied to other applications after minor alterations, such as preparation of optic, acoustic and solar harvesting materials and devices.

  6. Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method

    NARCIS (Netherlands)

    Verbaan, F.J.; Bal, S.M.; Berg, van den D.J.; Dijksman, J.A.; Hecke, van M.; Verpoorten, H.; Berg, van den A.; Luttge, R.; Bouwstra, J.A.

    2008-01-01

    An electrical applicator was designed, which can pierce short microneedles into the skin with a predefined velocity. Three different shapes of microneedles were used, namely 300 µm assembled hollow metal microneedle arrays, 300 µm solid metal microneedle arrays and 245 µm hollow silicon microneedle

  7. Experimental and Computational Analysis of Water-Droplet Formation and Ejection Process Using Hollow Microneedle

    Science.gov (United States)

    Kato, Norihisa; Oka, Ryotaro; Sakai, Takahiro; Shibata, Takayuki; Kawashima, Takahiro; Nagai, Moeto; Mineta, Takashi; Makino, Eiji

    2011-06-01

    In this paper, we present the possibility of liquid delivery using fabricated hollow silicon dioxide microneedles of approximately 2 µm in diameter. As a fundamental study, the water-droplet formation and ejection process was examined via dynamic observations during water ejection tests and computational fluid dynamics (CFD) analysis. The experimental results indicated that fluid flow in a microneedle follows the Hagen-Poiseuille law, i.e., the flow rate is approximately directly proportional to the fourth power of the inner diameter. Moreover, the ejection pressure and maximum droplet curvature obtained using the proposed microfluid ejection model were in good agreement with the experimental results. The resulting ejection pressure is equal to the theoretical pressure difference of a spherical droplet, which is determined using the Young-Laplace equation. The maximum curvature of a droplet formed at the tip of a microneedle can be estimated on the basis of the contact angle theory expressed by the Young equation.

  8. Arrays of hollow out-of-plane microneedles made by metal electrodeposition onto solvent cast conductive polymer structures

    International Nuclear Information System (INIS)

    Mansoor, I; Liu, Y; Stoeber, B; Häfeli, U O

    2013-01-01

    Transdermal drug delivery using microneedles is a technique to potentially replace hypodermic needles for injection of many vaccines and drugs. Fabrication of hollow metallic microneedles so far has been associated with time-consuming steps that restrict batch production of these devices. Here, we are presenting a novel method for making metallic microneedles with any desired height, spacing, and lumen size. In our process, we use solvent casting to coat a mold, which contains an array of pillars, with a conductive polymer composite layer. The conductive layer is then used as a seed layer in a metal electrodeposition process. To characterize the process, the conductivity of the polymer composite with respect to different filler concentrations was investigated. In addition, plasma etching of the polymer was characterized. The electroplating process was also studied further to control the thickness of the microneedle array plate. The strength of the microneedle devices was evaluated through a series of compression tests, while their performance for transdermal drug delivery was tested by injection of 2.28 µm fluorescent microspheres into animal skin. The fabricated metallic microneedles seem appropriate for subcutaneous delivery of drugs and microspheres. (paper)

  9. Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method

    NARCIS (Netherlands)

    Verbaan, F.J.; Bal, S.M.; van den Berg, D.J.; Dijksman, J.A.; van Hecke, M.; Verpoorten, H.; van den Berg, Albert; Lüttge, Regina; Bouwstra, J.A.

    2008-01-01

    An electrical applicator was designed, which can pierce short microneedles into the skin with a predefined velocity. Three different shapes of microneedles were used, namely 300 mu m assembled hollow metal microneedle arrays, 300 mu m solid metal microneedle arrays and 245 mu m hollow silicon

  10. Fabrication of Bonding-Type Hollow Microneedle Array by Injection Molding and Evaluation of its Puncture Characteristics

    Science.gov (United States)

    Ogai, Noriyuki; Sugimura, Ryo; Tamaru, Takuya; Takiguchi, Yoshihiro

    A microneedle array which consists from small needles compared to a conventional metal injection needle is expected as a low invasive transdermal medical treatment device, and many fabrication approach have been conducted. In this study, we fabricated plastic hollow microneedle array by a fabrication method based on the combination of injection molding, bonding and assembly techniques. To evaluate puncture characteristics of the fabricated needle, we measured a puncture force to silicone rubber by experimental equipment using loadcell and automatic stage. Furthermore, we propose and demonstrate a new method to measure actual punctured depth from punctured trace on the needle surface modified by O2 plasma treatment.

  11. Microneedles for drug and vaccine delivery

    Science.gov (United States)

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

    2012-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  12. Microneedle fabrication using the plane pattern to cross-section transfer method

    Science.gov (United States)

    Khumpuang, Sommawan; Horade, Mitsuhiro; Fujioka, Kazuya; Sugiyama, Susumu

    2006-04-01

    In this paper, microneedle fabrication using the PCT (plane pattern to cross-section transfer) method is summarized. Three types of microneedle array have been developed: the single-tip, quadruplet, and hollow microneedle arrays. A brief introduction to the fabrication process using PCT and detailed design concepts for optimizing the fabrication steps for shape improvement of the three types of microneedle are provided. The microneedle structures have controllable angled sidewalls, exhibiting an extraordinarily geometrical level of accuracy compared to what is achieved using other existing fabrication methods based on deep x-ray lithography by synchrotron radiation. Furthermore, the improvements reported in this work as compared to the results from the existing methods are: sharper tips for the single-tip microneedles, strength improvement for the quadruplet microneedles, and cost reduction for the hollow microneedles. Each type of microneedle was designed to serve a different biomedical need.

  13. Enhancement of Skin Permeation and Skin Immunization of Ovalbumin Antigen via Microneedles.

    Science.gov (United States)

    Pamornpathomkul, Boonnada; Rojanarata, Theerasak; Opanasopit, Praneet; Ngawhirunpat, Tanasait

    2017-10-01

    The purpose of this study was to evaluate the use of different types of microneedles and doses of ovalbumin antigen for in vitro skin permeation and in vivo immunization. In vitro skin permeation experiments and confocal laser scanning microscopy revealed that hollow microneedles had a superior enhancing effect on skin permeation compared with a solid microneedle patch and untreated skin by efficiently delivering ovalbumin-fluorescein conjugate into the deep skin layers. The flux and cumulative amount of ovalbumin-fluorescein conjugate at 8 h after administering with various conditions could be ranked as follows: hollow MN; high dose > medium dose > low dose > MN patch; high dose > medium dose > low dose > untreated skin; high dose > medium dose > low dose > without ovalbumin-fluorescein conjugate. As the dose of ovalbumin-fluorescein conjugate was increased to 500 μg, the antigen accumulated in the skin to a greater extent, as evidenced by the increasing green fluorescence intensity. When the hollow microneedle was used for the delivery of ovalbumin into the skin of mice, it was capable of inducing a stronger immunoglobulin G immune response than conventional subcutaneous injection at the same antigen dose. Immunoglobulin G levels in the hollow MN group were 5.7, 11.6, and 13.3 times higher than those of the subcutaneous injection group for low, medium, and high doses, respectively. Furthermore, the mice immunized using the hollow microneedle showed no signs of skin infection or pinpoint bleeding. The results suggest that the hollow MN is an efficient device for delivering the optimal dose of antigen via the skin for successful immunization.

  14. Minimally invasive and targeted therapeutic cell delivery to the skin using microneedle devices.

    Science.gov (United States)

    Gualeni, B; Coulman, S A; Shah, D; Eng, P F; Ashraf, H; Vescovo, P; Blayney, G J; Piveteau, L-D; Guy, O J; Birchall, J C

    2018-03-01

    Translation of cell therapies to the clinic is accompanied by numerous challenges, including controlled and targeted delivery of the cells to their site of action, without compromising cell viability and functionality. To explore the use of hollow microneedle devices (to date only used for the delivery of drugs and vaccines into the skin and for the extraction of biological fluids) to deliver cells into skin in a minimally invasive, user-friendly and targeted fashion. Melanocyte, keratinocyte and mixed epidermal cell suspensions were passed through various types of microneedles and subsequently delivered into the skin. Cell viability and functionality are maintained after injection through hollow microneedles with a bore size ≥ 75 μm. Healthy cells are delivered into the skin at clinically relevant depths. Hollow microneedles provide an innovative and minimally invasive method for delivering functional cells into the skin. Microneedle cell delivery represents a potential new treatment option for cell therapy approaches including skin repigmentation, wound repair, scar and burn remodelling, immune therapies and cancer vaccines. © 2017 British Association of Dermatologists.

  15. Handheld Microneedle-Based Electrolyte Sensing Platform.

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Philip R. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Rivas, Rhiana [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Johnson, David [Aquila Technologies Group, Inc., Albuquerque, NM (United States); Edwards, Thayne L. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Koskelo, Markku [Aquila Technologies Group, Inc., Albuquerque, NM (United States); Shawa, Luay [Aquila Technologies Group, Inc., Albuquerque, NM (United States); Brener, Igal [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Chavez, Victor H. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Polsky, Ronen [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    Sandia National Laboratories will provide technical assistance, within time and budget, to Requester on testing and analyzing a microneedle-based electrolyte sensing platform. Hollow microneedles will be fabricated at Sandia and integrated with a fluidic chip using plastic laminate prototyping technology available at Sandia. In connection with commercial ion selective electrodes the sensing platform will be tested for detection of electrolytes (sodium and/or potassium) within physiological relevant concent ration ranges.

  16. Fabrication of a Microneedle Using Human Hair

    Science.gov (United States)

    Yoshida, Yoshikazu; Takei, Tamotsu

    2009-09-01

    In this study, we developed a novel microneedle design to inject medication into the skin and to remove blood from a blood vessel. A drilling machine and chemicals were used to drill a hollow needle bore into the center of a strand of human hair. Our results demonstrate that a pen-shaped microneedle has been fabricated at a length of 1.1 mm, a base diameter of 80 µm, and a tip diameter of 40 µm. The hair microneedle was sufficiently strong to insert into the meat of a chicken leg.

  17. A high aspect ratio SU-8 fabrication technique for hollow microneedles for transdermal drug delivery and blood extraction

    Science.gov (United States)

    Chaudhri, Buddhadev Paul; Ceyssens, Frederik; De Moor, Piet; Van Hoof, Chris; Puers, Robert

    2010-06-01

    Protein drugs, e.g. hormonal drugs, cannot be delivered orally to a patient as they get digested in the gastro-intestinal (GI) tract. Thus, it is imperative that these kinds of drugs are delivered transdermally through the skin. To provide for real-time feedback as well as to test independently for various substances in the blood, we also need a blood sampling system. Microneedles can perform both these functions. Further, microneedles made of silicon or metal have the risk of breaking inside the skin thereby leading to complications. SU-8, being approved of as being biocompatible by the Food and Drug Agency (FDA) of the United States, is an attractive alternative because firstly it is a polymer material, thereby reducing the chances of breakages inside the skin, and secondly it is a negative photoresist, thereby leading to ease of fabrication. Thus, here we present very tall (around 1600 µm) SU-8 polymer-based hollow microneedles fabricated by a simple and repeatable process, which are a very good candidate for transdermal drug delivery as well as blood extraction. The paper elaborates on the details that allow the fabrication of such extreme aspect ratios (>100).

  18. A high aspect ratio SU-8 fabrication technique for hollow microneedles for transdermal drug delivery and blood extraction

    International Nuclear Information System (INIS)

    Chaudhri, Buddhadev Paul; Ceyssens, Frederik; Van Hoof, Chris; Puers, Robert; De Moor, Piet

    2010-01-01

    Protein drugs, e.g. hormonal drugs, cannot be delivered orally to a patient as they get digested in the gastro-intestinal (GI) tract. Thus, it is imperative that these kinds of drugs are delivered transdermally through the skin. To provide for real-time feedback as well as to test independently for various substances in the blood, we also need a blood sampling system. Microneedles can perform both these functions. Further, microneedles made of silicon or metal have the risk of breaking inside the skin thereby leading to complications. SU-8, being approved of as being biocompatible by the Food and Drug Agency (FDA) of the United States, is an attractive alternative because firstly it is a polymer material, thereby reducing the chances of breakages inside the skin, and secondly it is a negative photoresist, thereby leading to ease of fabrication. Thus, here we present very tall (around 1600 µm) SU-8 polymer-based hollow microneedles fabricated by a simple and repeatable process, which are a very good candidate for transdermal drug delivery as well as blood extraction. The paper elaborates on the details that allow the fabrication of such extreme aspect ratios (>100).

  19. Peri-tumor administration of 5-fluorouracil sol-gel using a hollow microneedle for treatment of gastric cancer.

    Science.gov (United States)

    Jung, Yoon Suk; Koo, Dong-Hoe; Yang, Jeong-Yoon; Lee, Hee-Young; Park, Jung-Hwan; Park, Jung Ho

    2018-11-01

    The aim of this study was to investigate the effectiveness of treating gastric cancer by injecting a pluronic F-127 sol-gel formulation of 5-fluorouracil (5-FU) into normal tissue surrounding the tumor using a hollow microneedle. The MTS tetrazolium assay was performed to assess the cytotoxicity of 5-FU after application to gastric cancer cells at different concentrations for 1, 5 and 10 h. Gastric cancer cells were inoculated subcutaneously into 30 male nude mice (CrjBALB/c-nu/nu mice, male); the inoculated mouse were divided into three groups. One group received no treatment, whereas the two other groups received free 5-FU gel (40 mg/kg) and 5-FU gel (40 mg/kg) for 4 days, respectively. Mean tumor volume, apoptotic index (TUNEL) and proliferative index (Ki 67) were evaluated in all groups. Cell viability was 77.3% when 1.22 g of free 5-FU was administered, whereas cell viability was 37.4% and 43.5% when 0.122 g of free 5-FU was administered per hour for 10 h and 0.244 g of free 5-FU was administered for 5 h (p sol-gel induced apoptosis and significantly inhibited cell proliferation compared to the free 5-FU (p sol-gel formulation to inoculated mice (p sol-gel formulation into normal tissue surrounding the tumor mass using a hollow microneedle is an effective method for treating gastric cancer.

  20. A novel microneedle array for the treatment of hydrocephalus.

    Science.gov (United States)

    Oh, Jonghyun; Liu, Kewei; Medina, Tim; Kralick, Francis; Noh, Hongseok Moses

    2014-06-01

    We present a microfabricated 10 by 10 array of microneedles for the treatment of a neurological disease called communicating hydrocephalus. Together with the previously reported microvalve array, the current implantable microneedle array completes the microfabricated arachnoid granulations (MAGs) that mimic the function of normal arachnoid granulations (AGs). The microneedle array was designed to enable the fixation of the MAGs through dura mater membrane in the brain and thus provide a conduit for the flow of cerebrospinal fluid (CSF). Cone-shaped microneedles with hollow channels were fabricated using a series of microfabrication techniques: SU-8 photolithography for tapered geometry, reactive ion etching for sharpening the microneedles, 248 nm deep UV excimer laser machining for creating through-hole inside the microneedles, and metal sputtering for improved rigidity. Puncture tests were conducted using porcine dura mater and the results showed that the fabricated microneedle array is strong enough to pierce the dura mater. The in-vitro biocompatibility test result showed that none of the 100 outlets of the microneedles exposed to the bloodstream were clogged significantly by blood cells. We believe that these test results demonstrate the potential use of the microneedle array as a new treatment of hydrocephalus.

  1. Immunogenicity of diphtheria toxoid and poly(I:C) loaded cationic liposomes after hollow microneedle-mediated intradermal injection in mice.

    Science.gov (United States)

    Du, Guangsheng; Leone, Mara; Romeijn, Stefan; Kersten, Gideon; Jiskoot, Wim; Bouwstra, Joke A

    2018-06-02

    In this study, we aimed to investigate the immunogenicity of cationic liposomes loaded with diphtheria toxoid (DT) and poly(I:C) after hollow microneedle-mediated intradermal vaccination in mice. The following liposomal formulations were studied: DT loaded liposomes, a mixture of free DT and poly(I:C)-loaded liposomes, a mixture of DT-loaded liposomes and free poly(I:C), and liposomal formulations with DT and poly(I:C) either individually or co-encapsulated in the liposomes. Reference groups were DT solution adjuvanted with or without poly(I:C) (DT/poly(I:C)). The liposomal formulations were characterized in terms of particle size, zeta potential, loading and release of DT and poly(I:C). After intradermal injection of BALB/c mice with the formulations through a hollow microneedle, the immunogenicity was assessed by DT-specific ELISAs. All formulations induced similar total IgG and IgG1 titers. However, all the liposomal groups containing both DT and poly(I:C) showed enhanced IgG2a titers compared to DT/poly(I:C) solution, indicating that the immune response was skewed towards a Th1 direction. This enhancement was similar for all liposomal groups that contain both DT and poly(I:C) in the formulations. Our results reveal that a mixture of DT encapsulated liposomes and poly(I:C) encapsulated liposomes have a similar effect on the antibody responses as DT and poly(I:C) co-encapsulated liposomes. These findings may have implications for future design of liposomal vaccine delivery systems. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Drawing lithography for microneedles: a review of fundamentals and biomedical applications.

    Science.gov (United States)

    Lee, Kwang; Jung, Hyungil

    2012-10-01

    A microneedle is a three-dimensional (3D) micromechanical structure and has been in the spotlight recently as a drug delivery system (DDS). Because a microneedle delivers the target drug after penetrating the skin barrier, the therapeutic effects of microneedles proceed from its 3D structural geometry. Various types of microneedles have been fabricated using subtractive micromanufacturing methods which are based on the inherently planar two-dimensional (2D) geometries. However, traditional subtractive processes are limited for flexible structural microneedles and makes functional biomedical applications for efficient drug delivery difficult. The authors of the present study propose drawing lithography as a unique additive process for the fabrication of a microneedle directly from 2D planar substrates, thus overcoming a subtractive process shortcoming. The present article provides the first overview of the principal drawing lithography technology: fundamentals and biomedical applications. The continuous drawing technique for an ultrahigh-aspect ratio (UHAR) hollow microneedle, stepwise controlled drawing technique for a dissolving microneedle, and drawing technique with antidromic isolation for a hybrid electro-microneedle (HEM) are reviewed, and efficient biomedical applications by drawing lithography-mediated microneedles as an innovative drug and gene delivery system are described. Drawing lithography herein can provide a great breakthrough in the development of materials science and biotechnology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Hydrodynamic gene delivery in human skin using a hollow microneedle device

    OpenAIRE

    Dul, M.; Stefanidou, M.; Porta, P.; Serve, J.; O'Mahony, Conor; Malissen, B.; Henri, S.; Levin, Y.; Kochba, E.; Wong, F. S.; Dayan, C.; Coulman, S. A.; Birchall, J. C.

    2017-01-01

    Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potenti...

  4. Low-Cost Fabrication of Hollow Microneedle Arrays Using CNC Machining and UV Lithography

    DEFF Research Database (Denmark)

    Lê Thanh, Hoà; Ta, B.Q.; Le The, H.

    2015-01-01

    In order to produce disposable microneedles for blood-collection devices in smart homecare monitoring systems, we have developed a simple low-cost scalable process for mass fabrication of sharp-tipped microneedle arrays. The key feature in this process is a design of computer numerical control......-machined aluminum sample (CAS). The inclined sidewalls on the CAS enable microfabricated traditional-shaped microneedles (TMNs) to be produced in the desired shape. This process provides significant advantages over other methods that use inclined lithography or anisotropic wet etching. TMNs with a length of 1510 mu...

  5. Design, modeling and simulation of MEMS-based silicon Microneedles

    International Nuclear Information System (INIS)

    Amin, F; Ahmed, S

    2013-01-01

    The advancement in semiconductor process engineering and nano-scale fabrication technology has made it convenient to transport specific biological fluid into or out of human skin with minimum discomfort. Fluid transdermal delivery systems such as Microneedle arrays are one such emerging and exciting Micro-Electro Mechanical System (MEMS) application which could lead to a total painless fluid delivery into skin with controllability and desirable yield. In this study, we aimed to revisit the problem with modeling, design and simulations carried out for MEMS based silicon hollow out of plane microneedle arrays for biomedical applications particularly for transdermal drug delivery. An approximate 200 μm length of microneedle with 40 μm diameter of lumen has been successfully shown formed by isotropic and anisotropic etching techniques using MEMS Pro design tool. These microneedles are arranged in size of 2 × 4 matrix array with center to center spacing of 750 μm. Furthermore, comparisons for fluid flow characteristics through these microneedle channels have been modeled with and without the contribution of the gravitational forces using mathematical models derived from Bernoulli Equation. Physical Process simulations have also been performed on TCAD SILVACO to optimize the design of these microneedles aligned with the standard Si-Fabrication lines.

  6. Design, modeling and simulation of MEMS-based silicon Microneedles

    Science.gov (United States)

    Amin, F.; Ahmed, S.

    2013-06-01

    The advancement in semiconductor process engineering and nano-scale fabrication technology has made it convenient to transport specific biological fluid into or out of human skin with minimum discomfort. Fluid transdermal delivery systems such as Microneedle arrays are one such emerging and exciting Micro-Electro Mechanical System (MEMS) application which could lead to a total painless fluid delivery into skin with controllability and desirable yield. In this study, we aimed to revisit the problem with modeling, design and simulations carried out for MEMS based silicon hollow out of plane microneedle arrays for biomedical applications particularly for transdermal drug delivery. An approximate 200 μm length of microneedle with 40 μm diameter of lumen has been successfully shown formed by isotropic and anisotropic etching techniques using MEMS Pro design tool. These microneedles are arranged in size of 2 × 4 matrix array with center to center spacing of 750 μm. Furthermore, comparisons for fluid flow characteristics through these microneedle channels have been modeled with and without the contribution of the gravitational forces using mathematical models derived from Bernoulli Equation. Physical Process simulations have also been performed on TCAD SILVACO to optimize the design of these microneedles aligned with the standard Si-Fabrication lines.

  7. Draft Title V Operating Permit: Andeavor Field Services, LLC - Walker Hollow Compressor Station

    Science.gov (United States)

    Draft Operating Permit (Permit Number: V-UO-000979-2017.00), statement of basis, public notice bulletin, and the administrative permit docket (application and other supporting documents) for the Andeavor Walker Hollow Compressor Station.

  8. Draft Title V Operating Permit: Andeavor Field Services, LLC - Walker Hollow Compressor Station

    Science.gov (United States)

    Draft Title V Operating Permit, statement of basis, public notice bulletin, and the administrative permit docket (application and other supporting documents) for the Draft Part 71 Permit for Andeavor Field Services, LLC - Walker Hollow CS.

  9. Infusion pressure and pain during microneedle injection into skin of human subjects

    Science.gov (United States)

    Gupta, Jyoti; Park, Sohyun; Bondy, Brian; Felner, Eric I.; Prausnitz, Mark R.

    2011-01-01

    Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures cause more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. PMID:21684001

  10. Hollow agarose microneedle with silver coating for intradermal surface-enhanced Raman measurements: a skin-mimicking phantom study

    Science.gov (United States)

    Yuen, Clement; Liu, Quan

    2015-06-01

    Human intradermal components contain important clinical information beneficial to the field of immunology and disease diagnosis. Although microneedles have shown great potential to act as probes to break the human skin barrier for the minimally invasive measurement of intradermal components, metal microneedles that include stainless steel could cause the following problems: (1) sharp waste production, and (2) contamination due to reuse of microneedles especially in developing regions. In this study, we fabricate agarose microneedles coated with a layer of silver (Ag) and demonstrate their use as a probe for the realization of intradermal surface-enhanced Raman scattering measurements in a set of skin-mimicking phantoms. The Ag-coated agarose microneedle quantifies a range of glucose concentrations from 5 to 150 mM inside the skin phantoms with a root-mean-square error of 5.1 mM within 10 s. The needle is found enlarged by 53.9% after another 6 min inside the phantom. The shape-changing capability of this agarose microneedle ensures that the reuse of these microneedles is impossible, thus avoiding sharp waste production and preventing needle contamination, which shows the great potential for safe and effective needle-based measurements.

  11. A microneedle biosensor for minimally-invasive transdermal detection of nerve agents.

    Science.gov (United States)

    Mishra, Rupesh K; Vinu Mohan, A M; Soto, Fernando; Chrostowski, Robert; Wang, Joseph

    2017-03-13

    A microneedle electrochemical biosensor for the minimally invasive detection of organophosphate (OP) chemical agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a hollow-microneedle modified carbon-paste array electrode transducer, and involves rapid square-wave voltammetric (SWV) measurements of the p-nitrophenol product of the OPH enzymatic reaction in the presence of the OP substrate. The scanning-potential SWV transduction mode offers an additional dimension of selectivity compared to common fixed-potential OPH-amperometric biosensors. The microneedle device offers a highly linear response for methyl paraoxon (MPOx) over the range of 20-180 μM, high selectivity in the presence of excess co-existing ascorbic acid and uric acid and a high stability sensor upon exposure to the interstitial fluid (ISF). The OPH microneedle sensor was successfully tested ex vivo using mice skin samples exposed to MPOx, demonstrating its promise for minimally-invasive monitoring of OP agents and pesticides and as a wearable sensor for detecting toxic compounds, in general.

  12. From the Cover: Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies

    Science.gov (United States)

    McAllister, Devin V.; Wang, Ping M.; Davis, Shawn P.; Park, Jung-Hwan; Canatella, Paul J.; Allen, Mark G.; Prausnitz, Mark R.

    2003-11-01

    Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 μm. When solid microneedles were used, skin permeability was increased in vitro by orders of magnitude for macromolecules and particles up to 50 nm in radius. Intracellular delivery of molecules into viable cells was also achieved with high efficiency. Hollow microneedles permitted flow of microliter quantities into skin in vivo, including microinjection of insulin to reduce blood glucose levels in diabetic rats. transdermal drug delivery | skin | microelectromechanical systems | solid microneedle | hollow needle injection

  13. Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays.

    Science.gov (United States)

    van der Maaden, Koen; Luttge, Regina; Vos, Pieter Jan; Bouwstra, Joke; Kersten, Gideon; Ploemen, Ivo

    2015-08-01

    In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific and patent literature is reviewed, and we focus on the possibilities and constraints of porous microneedle technologies for dermal drug delivery. Furthermore, we show preliminary data with commercially available porous microneedles and describe future directions in this field of research.

  14. Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays

    OpenAIRE

    Maaden, van der, Koen; Lüttge, R Regina; Vos, PJW; Bouwstra, Joke A; Kersten, Gideon FA; Ploemen, IHJ Ingmar

    2015-01-01

    In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific an...

  15. Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward Melanoma Screening.

    Science.gov (United States)

    Ciui, Bianca; Martin, Aida; Mishra, Rupesh K; Brunetti, Barbara; Nakagawa, Tatsuo; Dawkins, Thomas J; Lyu, Mengjia; Cristea, Cecilia; Sandulescu, Robert; Wang, Joseph

    2018-04-01

    Wearable bendable bandage-based sensor and a minimally invasive microneedle biosensor are described toward rapid screening of skin melanoma. These wearable electrochemical sensors are capable of detecting the presence of the tyrosinase (TYR) enzyme cancer biomarker in the presence of its catechol substrate, immobilized on the transducer surface. In the presence of the surface TYR biomarker, the immobilized catechol is rapidly converted to benzoquinone that is detected amperometrically, with a current signal proportional to the TYR level. The flexible epidermal bandage sensor relies on printing stress-enduring inks which display good resiliency against mechanical deformations, whereas the hollow microneedle device is filled with catechol-coated carbon paste for assessing tissue TYR levels. The bandage sensor can thus be used directly on the skin whereas microneedle device can reach melanoma tissues under the skin. Both wearable sensors are interfaced to an ultralight flexible electronic board, which transmits data wirelessly to a mobile device. The analytical performance of the resulting bandage and microneedle sensing systems are evaluated using TYR-containing agarose phantom gel and porcine skin. The new integrated conformal portable sensing platforms hold considerable promise for decentralized melanoma screening, and can be extended to the screening of other key biomarkers in skin moles. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. A microfluidic distribution system for an array of hollow microneedles

    International Nuclear Information System (INIS)

    Hoel, Antonin; Jullien, Marie-Caroline; Baron, Nolwenn; Cabodevila, Gonzalo

    2008-01-01

    We report a microfluidic device able to control the ejection of fluid through a matrix of out-of-plane microneedles. The device comprises a matrix of open dispensing units connected to needles and filled by a common filling system. A deformable membrane (e.g. in PDMS) is brought into contact with the dispensing units. Pressure exerted on the deformable membrane closes (and thus individualizes) each dispensing unit and provokes the ejection of the dispensing unit content through the outlets. Sufficient pressure over the deformable membrane ensures that all dispensing units deliver a fixed volume (their content) irrespective of the hydrodynamic pressure outside the dispensing unit outlet. The size of the ensemble matrix of dispensing units, the number of liquid reservoirs, as well as the material can vary depending on the considered application of the device or on the conditions of use. In the present paper, the liquid reservoirs are geometrically identical. The geometrical parameters of the device are optimized to avoid as much dead volume as possible, as it was to handle plasmid DNA solutions which are very expensive. The conception, the fabrication and the experimental results are described in this paper. Our prototype is conceived to inject in a uniform way 10 µl of drug through 100 microneedles distributed over 1 cm 2

  17. Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

    Science.gov (United States)

    Kumar, Amit; Li, Xinran; Sandoval, Michael A; Rodriguez, B Leticia; Sloat, Brian R; Cui, Zhengrong

    2011-01-01

    Background: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection. Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli, but the extent of the permeation was not greater than that enabled by hypodermic injection. Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection. PMID:21753877

  18. Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing.

    Science.gov (United States)

    Rajabi, Mina; Roxhed, Niclas; Shafagh, Reza Zandi; Haraldson, Tommy; Fischer, Andreas Christin; Wijngaart, Wouter van der; Stemme, Göran; Niklaus, Frank

    2016-01-01

    This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.

  19. Fiberoptic microneedles: novel optical diffusers for interstitial delivery of therapeutic light.

    Science.gov (United States)

    Kosoglu, Mehmet A; Hood, Robert L; Rossmeisl, John H; Grant, David C; Xu, Yong; Robertson, John L; Rylander, Marissa Nichole; Rylander, Christopher G

    2011-11-01

    Photothermal therapies have limited efficacy and application due to the poor penetration depth of light inside tissue. In earlier work, we described the development of novel fiberoptic microneedles to provide a means to mechanically penetrate dermal tissue and deliver light directly into a localized target area.This paper presents an alternate fiberoptic microneedle design with the capability of delivering more diffuse, but therapeutically useful photothermal energy. Laser lipolysis is envisioned as a future clinical application for this design. A novel fiberoptic microneedle was developed using hydrofluoric acid etching of optical fiber to permit diffuse optical delivery. Microneedles etched for 10, 30, and 50 minutes, and an optical fiber control were compared with three techniques. First, red light delivery from the microneedles was evaluated by imaging the reflectance of the light from a white paper.Second, spatial temperature distribution of the paper in response to near-IR light (1,064 nm, 1 W CW) was recorded using infrared thermography. Third, ex vivo adipose tissue response during 1,064 nm, (5 W CW)irradiation was recorded with bright field microscopy. Acid etching exposed a 3 mm length of the fiber core, allowing circumferential delivery of light along this length. Increasing etching time decreased microneedle diameter, resulting in increased uniformity of red and 1,064 nm light delivery along the microneedle axis. For equivalent total energy delivery, thinner microneedles reduced carbonization in the adipose tissue experiments. We developed novel microscale optical diffusers that provided a more homogeneous light distribution from their surfaces, and compared performance to a flat-cleaved fiber, a device currently utilized in clinical practice. These fiberoptic microneedles can potentially enhance clinical laser procedures by providing direct delivery of diffuse light to target chromophores, while minimizing undesirable photothermal damage in adjacent

  20. Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

    Directory of Open Access Journals (Sweden)

    Kumar A

    2011-06-01

    Full Text Available Amit Kumar, Xinran Li, Michael A Sandoval, B Leticia Rodriguez, Brian R Sloat, Zhengrong CuiUniversity of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, USABackground: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection.Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli, but the extent of the permeation was not greater than that enabled by hypodermic injection.Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection.Keywords: antibody responses, safety of microneedles, transepidermal water loss

  1. Drug delivery through microneedles

    NARCIS (Netherlands)

    Luttge, R.; Dietzel, A.

    2016-01-01

    Drug delivery through microneedles is a new form of a pharmaceutical dosage system. While single microneedles have been clinically applied already, the out-of-plane integration of a multitude of microneedles in a pharmaceutical patch is a disruptive technology. To take advantage of micro- and

  2. Silicon micromachined hollow microneedles for transdermal liquid transport

    NARCIS (Netherlands)

    Gardeniers, J.G.E.; Luttge, R.; Berenschot, J.W.; Boer, de M.J.; Yeshurun, S.Y.; Hefetz, M.; Oever, van't R.; Berg, van den A.

    2003-01-01

    This paper presents a novel process for the fabrication of out-of-plane hollow micro needles in silicon. The fabrication method consists of a sequence of deep-reactive ion etching (DRIE), anisotropic wet etching and conformal thin film deposition, and allows needle shapes with different,

  3. Effect of microneedle geometry and supporting substrate on microneedle array penetration into skin.

    Science.gov (United States)

    Kochhar, Jaspreet Singh; Quek, Ten Cheer; Soon, Wei Jun; Choi, Jaewoong; Zou, Shui; Kang, Lifeng

    2013-11-01

    Microneedles are being fast recognized as a useful alternative to injections in delivering drugs, vaccines, and cosmetics transdermally. Owing to skin's inherent elastic properties, microneedles require an optimal geometry for skin penetration. In vitro studies, using rat skin to characterize microneedle penetration in vivo, require substrates with suitable mechanical properties to mimic human skin's subcutaneous tissues. We tested the effect of these two parameters on microneedle penetration. Geometry in terms of center-to-center spacing of needles was investigated for its effect on skin penetration, when placed on substrates of different hardness. Both hard (clay) and soft (polydimethylsiloxane, PDMS) substrates underneath rat skin and full-thickness pig skin were used as animal models and human skins were used as references. It was observed that there was an increase in percentage penetration with an increase in needle spacing. Microneedle penetration with PDMS as a support under stretched rat skin correlated better with that on full-thickness human skin, while penetration observed was higher when clay was used as a substrate. We showed optimal geometries for efficient penetration together with recommendation for a substrate that could better mimic the mechanical properties of human subcutaneous tissues, when using microneedles fabricated from poly(ethylene glycol)-based materials. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Rapid fabrication of microneedles using magnetorheological drawing lithography.

    Science.gov (United States)

    Chen, Zhipeng; Ren, Lei; Li, Jiyu; Yao, Lebin; Chen, Yan; Liu, Bin; Jiang, Lelun

    2018-01-01

    Microneedles are micron-sized needles that are widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. In this study, we present a novel magnetorheological drawing lithography (MRDL) method to efficiently fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. With the assistance of an external magnetic field, the 3D structure of a microneedle can be directly drawn from a droplet of curable magnetorheological fluid. The formation process of a microneedle consists of two key stages, elasto-capillary self-thinning and magneto-capillary self-shrinking, which greatly affect the microneedle height and tip radius. Penetration and fracture tests demonstrated that the microneedle had sufficient strength and toughness for skin penetration. Microneedle arrays and a bio-inspired microneedle were also fabricated, which further demonstrated the versatility and flexibility of the MRDL method. Microneedles have been widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. Furthermore, most researchers have focused on the biomedical applications of microneedles but have given little attention to the optimization of the fabrication process. This research presents a novel magnetorheological drawing lithography (MRDL) method to fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. In this proposed technique, a droplet of curable magnetorheological fluid (CMRF) is drawn directly from almost any substrate to produce a 3D microneedle under an external magnetic field. This method not only inherits the advantages of thermal drawing approach without the need for a mask

  5. Microneedle array electrode for human EEG recording.

    NARCIS (Netherlands)

    Lüttge, Regina; van Nieuwkasteele-Bystrova, Svetlana Nikolajevna; van Putten, Michel Johannes Antonius Maria; Vander Sloten, Jos; Verdonck, Pascal; Nyssen, Marc; Haueisen, Jens

    2009-01-01

    Microneedle array electrodes for EEG significantly reduce the mounting time, particularly by circumvention of the need for skin preparation by scrubbing. We designed a new replication process for numerous types of microneedle arrays. Here, polymer microneedle array electrodes with 64 microneedles,

  6. Parameter optimization toward optimal microneedle-based dermal vaccination.

    Science.gov (United States)

    van der Maaden, Koen; Varypataki, Eleni Maria; Yu, Huixin; Romeijn, Stefan; Jiskoot, Wim; Bouwstra, Joke

    2014-11-20

    Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles. Microneedles are used to deliver a drug into the skin in a minimally-invasive and potentially pain free manner. Besides, the skin is a potent immune organ that is highly suitable for vaccination. However, there are several factors that influence the penetration ability of the skin by microneedles and the immune responses upon microneedle-based immunization. In this study we assessed several different microneedle arrays for their ability to penetrate ex vivo human skin by using trypan blue and (fluorescently or radioactively labeled) ovalbumin. Next, these different microneedles and several factors, including the dose of ovalbumin, the effect of using an impact-insertion applicator, skin location of microneedle application, and the area of microneedle application, were tested in vivo in mice. The penetration ability and the dose of ovalbumin that is delivered into the skin were shown to be dependent on the use of an applicator and on the microneedle geometry and size of the array. Besides microneedle penetration, the above described factors influenced the immune responses upon microneedle-based vaccination in vivo. It was shown that the ovalbumin-specific antibody responses upon microneedle-based vaccination could be increased up to 12-fold when an impact-insertion applicator was used, up to 8-fold when microneedles were applied over a larger surface area, and up to 36-fold dependent on the location of microneedle application. Therefore, these influencing factors should be considered to optimize microneedle-based dermal immunization technologies. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Microneedle Platforms for Cell Analysis

    KAUST Repository

    Kavaldzhiev, Mincho

    2017-11-01

    Micro-needle platforms are the core components of many recent drug delivery and gene-editing techniques, which allow for intracellular access, controlled cell membrane stress or mechanical trapping of the nucleus. This dissertation work is devoted to the development of micro-needle platforms that offer customized fabrication and new capabilities for enhanced cell analyses. The highest degree of geometrical flexibility is achieved with 3D printed micro-needles, which enable optimizing the topographical stress environment for cells and cell populations of any size. A fabrication process for 3D-printed micro-needles has been developed as well as a metal coating technique based on standard sputter deposition. This extends the functionalities of the platforms by electrical as well as magnetic features. The micro-needles have been tested on human colon cancer cells (HCT116), showing a high degree of biocompatibility of the platform. Moreover, the capabilities of the 3D-printed micro-needles have been explored for drug delivery via the well-established electroporation technique, by coating the micro-needles with gold. Antibodies and fluorescent dyes have been delivered to HCT116 cells and human embryonic kidney cells with a very high transfection rate up to 90%. In addition, the 3D-printed electroporation platform enables delivery of molecules to suspended cells or adherent cells, with or without electroporation buffer solution, and at ultra-low voltages of 2V. In order to provide a micro-needle platform that exploits existing methods for mass fabrication a custom designed template-based process has been developed. It has been used for the production of gold, iron, nickel and poly-pyrrole micro-needles on silicon and glass substrates. A novel delivery method is introduced that activates the micro-needles by electromagnetic induction, which enables to wirelessly gain intracellular access. The method has been successfully tested on HCT116 cells in culture, where a time

  8. Microneedle, bio-microneedle and bio-inspired microneedle: A review.

    Science.gov (United States)

    Ma, Guojun; Wu, Chengwei

    2017-04-10

    Microneedles (MNs) are micro-scale needles used for drug delivery and other targets. Micro-scale size endows them with many advantages over hypodermic needles, including painlessness, minimal invasiveness and convenient operation, but it may also lead to risk of mechanical failures, which should be prevented in the clinical applications of MNs. The objective of this review is mainly to introduce studies on the mechanics problems with respect to MNs. Firstly, the basic knowledge of MNs is introduced in brief, so that readers can understand the basic characteristics of MNs. Secondly, researches on inserting behavior and mechanical performances of MNs are discussed. Thirdly, literatures on the drug delivery and the pain resulted from the insertion of MNs are overviewed. Finally, some bio-microneedles and bio-inspired MNs are introduced. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Dissolving Microneedle Patches for Dermal Vaccination.

    Science.gov (United States)

    Leone, M; Mönkäre, J; Bouwstra, J A; Kersten, G

    2017-11-01

    The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (e.g. pain, needle-stick injuries or needle re-use). This review focuses on dissolving microneedles that after penetration into the skin dissolve releasing the encapsulated antigen. The microneedle patch fabrication techniques and their challenges are discussed as well as the microneedle characterization methods and antigen stability aspects. The immunogenicity of antigens formulated in dissolving microneedles are addressed. Finally, the early clinical development is discussed.

  10. Collection of analytes from microneedle patches.

    Science.gov (United States)

    Romanyuk, Andrey V; Zvezdin, Vasiliy N; Samant, Pradnya; Grenader, Mark I; Zemlyanova, Marina; Prausnitz, Mark R

    2014-11-04

    Clinical medicine and public health would benefit from simplified acquisition of biological samples from patients that can be easily obtained at point of care, in the field, and by patients themselves. Microneedle patches are designed to serve this need by collecting dermal interstitial fluid containing biomarkers without the dangers, pain, or expertise needed to collect blood. This study presents novel methods to collect biomarker analytes from microneedle patches for analysis by integration into conventional analytical laboratory microtubes and microplates. Microneedle patches were made out of cross-linked hydrogel composed of poly(methyl vinyl ether-alt-maleic acid) and poly(ethylene glycol) prepared by micromolding. Microneedle patches were shown to swell with water up to 50-fold in volume, depending on degree of polymer cross-linking, and to collect interstitial fluid from the skin of rats. To collect analytes from microneedle patches, the patches were mounted within the cap of microcentrifuge tubes or formed the top of V-bottom multiwell microplates, and fluid was collected in the bottom of the tubes under gentle centrifugation. In another method, microneedle patches were attached to form the bottom of multiwell microplates, thereby enabling in situ analysis. The simplicity of biological sample acquisition using microneedle patches coupled with the simplicity of analyte collection from microneedles patches integrated into conventional analytical equipment could broaden the reach of future screening, diagnosis, and monitoring of biomarkers in healthcare and environmental/workplace settings.

  11. MICRONEEDLE STRUCTURE DESIGN AND OPTIMIZATION USING GENETIC ALGORITHM

    OpenAIRE

    N. A. ISMAIL; S. C. NEOH; N. SABANI; B. N. TAIB

    2015-01-01

    This paper presents a Genetic Algorithm (GA) based microneedle design and analysis. GA is an evolutionary optimization technique that mimics the natural biological evolution. The design of microneedle structure considers the shape of microneedle, material used, size of the array, the base of microneedle, the lumen base, the height of microneedle, the height of the lumen, and the height of the drug container or reservoir. The GA is executed in conjunction with ANSYS simulation system to assess...

  12. Acceptability of microneedle-patch vaccines: A qualitative analysis of the opinions of parents.

    Science.gov (United States)

    Marshall, S; Fleming, A; Moore, A C; Sahm, L J

    2017-09-05

    method. Participants in this study remained tentative. However, the study has also revealed that endorsement by healthcare professionals could reduce this tentativeness, thereby identifying the role of healthcare professionals in disseminating information and providing support to parents. An increased awareness of developments in microneedle technology is needed to permit informed decision-making by parents. Copyright © 2017. Published by Elsevier Ltd.

  13. Droplet-born air blowing: novel dissolving microneedle fabrication.

    Science.gov (United States)

    Kim, Jung Dong; Kim, Miroo; Yang, Huisuk; Lee, Kwang; Jung, Hyungil

    2013-09-28

    The microneedle-mediated drug delivery system has been developed to provide painless self-administration of drugs in a patient-friendly manner. Current dissolving microneedle fabrication methods, however, require harsh conditions for biological drugs and also have problems standardizing the drug dose. Here, we suggested the droplet-born air blowing (DAB) method, which provides gentle (4-25 °C) and fast (≤10min) microneedle fabrication conditions without drug loss. The amount of drug in the microneedle can be controlled by the pressure and time of droplet dispenser and the air blowing shapes this droplet to the microneedle, providing a force sufficient to penetrate skin. Also, the introduction of a base structure of two layered DAB-microneedle could provide complete drug delivery without wasting of drug. The DAB-based insulin loaded microneedle shows similar bioavailability (96.6±2.4%) and down regulation of glucose level compared with subcutaneous injection. We anticipate that DAB described herein will be suitable to design dissolving microneedles for use in biological drug delivery to patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. MICRONEEDLE STRUCTURE DESIGN AND OPTIMIZATION USING GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    N. A. ISMAIL

    2015-07-01

    Full Text Available This paper presents a Genetic Algorithm (GA based microneedle design and analysis. GA is an evolutionary optimization technique that mimics the natural biological evolution. The design of microneedle structure considers the shape of microneedle, material used, size of the array, the base of microneedle, the lumen base, the height of microneedle, the height of the lumen, and the height of the drug container or reservoir. The GA is executed in conjunction with ANSYS simulation system to assess the design specifications. The GA uses three operators which are reproduction, crossover and mutation to manipulate the genetic composition of the population. In this research, the microneedle is designed to meet a number of significant specifications such as nodal displacement, strain energy, equivalent stress and flow rate of the fluid / drug that flow through its channel / lumen. A comparison study is conducted to investigate the design of microneedle structure with and without the implementation of GA model. The results showed that GA is able to optimize the design parameters of microneedle and is capable to achieve the required specifications with better performance.

  15. Microfabricated Silicon Microneedle Array for Transdermal Drug Delivery

    International Nuclear Information System (INIS)

    Ji, J; Tay, F E; Miao Jianmin; Iliescu, C

    2006-01-01

    This paper presents developed processes for silicon microneedle arrays microfabrication. Three types of microneedles structures were achieved by isotropic etching in inductively coupled plasma (ICP) using SF 6 /O 2 gases, combination of isotropic etching with deep etching, and wet etching, respectively. A microneedle array with biodegradable porous tips was further developed based on the fabricated microneedles

  16. Microfabricated Silicon Microneedle Array for Transdermal Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Ji, J [Mechanical Engineering National University of Singapore, 119260, Singapore (Singapore); Tay, F E [Mechanical Engineering National University of Singapore, 119260, Singapore (Singapore); Miao Jianmin [MicroMachines Center, School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798 (Singapore); Iliescu, C [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Nanos, 04-01, 138669 (Singapore)

    2006-04-01

    This paper presents developed processes for silicon microneedle arrays microfabrication. Three types of microneedles structures were achieved by isotropic etching in inductively coupled plasma (ICP) using SF{sub 6}/O{sub 2} gases, combination of isotropic etching with deep etching, and wet etching, respectively. A microneedle array with biodegradable porous tips was further developed based on the fabricated microneedles.

  17. Microneedle delivery: clinical studies and emerging medical applications.

    Science.gov (United States)

    Pettis, Ronald J; Harvey, Alfred J

    2012-03-01

    The concept of microneedle drug delivery was described three decades ago; however, effective clinical demonstration has only occurred within the past 10-15 years. Substantial progress in microneedle design and fabrication including extensive in vitro, ex vivo, and in vivo preclinical evaluation with various drugs, vaccines and other agents has transpired over the last decade. In contrast with this large volume of preclinical data, there are relatively few published microneedle clinical studies. To date, the clinical investigative focus has included testing to reduce dermal barrier properties and enhance transdermal delivery; evaluation of enhanced vaccine antigenicity, including development of the first commercial microneedle product for intradermal influenza vaccination; evaluation of altered microneedle protein pharmacokinetics and pharmacodynamics, especially for insulin; and evaluation of the pain and other perceptions associated with microneedle usage. This review summarizes the various aspects of microneedle clinical evaluation to date and identifies areas requiring further clinical evaluation.

  18. The Troy Microneedle: A Rapidly Separating, Dissolving Microneedle Formed by Cyclic Contact and Drying on the Pillar (CCDP).

    Science.gov (United States)

    Kim, Miroo; Yang, Huisuk; Kim, Suyong; Lee, Chisong; Jung, Hyungil

    2015-01-01

    In dissolving microneedle (DMN)-mediated therapy, complete and rapid delivery of DMNs is critical for the desired efficacy. Traditional patch-based DMN delivery, however, may fail due to incomplete delivery from insufficient skin insertion or rapid separation of microneedles due to their strong bond to the backing film. Here, we introduce the Troy microneedle, which was created by cyclic contact and drying on the pillar (CCDP), and which enabled simultaneous complete and rapid delivery of DMN. This CCDP process could be flexibly repeated to achieve a specific desired drug dose in a DMN. We evaluated DMN separation using agarose gel, and the Troy microneedle achieved more complete and rapid separation than other, more deeply dipped DMN, primarily because of the Troy's minimal junction between the DMN and pillar. When Troy microneedles were applied to pig cadaver skin, it took only 15 s for over 90% of encapsulated rhodamine B to be delivered, compared to 2 h with application of a traditional DMN patch. In vivo skin penetration studies demonstrated rapid DMN-separation of Troy microneedles still in solid form before dissolution. The Troy microneedle overcomes critical issues associated with the low penetration efficiency of flat patch-based DMN and provides an innovative route for DMN-mediated therapy, combining patient convenience with the desire drug efficacy.

  19. Microneedle Platforms for Cell Analysis

    KAUST Repository

    Kavaldzhiev, Mincho

    2017-01-01

    to the development of micro-needle platforms that offer customized fabrication and new capabilities for enhanced cell analyses. The highest degree of geometrical flexibility is achieved with 3D printed micro-needles, which enable optimizing the topographical stress

  20. Microneedle Patches as Drug and Vaccine Delivery Platform.

    Science.gov (United States)

    Li, Junwei; Zeng, Mingtao; Shan, Hu; Tong, Chunyi

    2017-01-01

    Transcutaneous delivery is the ideal method for delivering therapeutic reagents or vaccines into skin. With their promise of self-administration, cost-effective and high efficiency, microneedle patches have been studied intensively as therapeutic and vaccination delivery platform that replaces injection by syringe. This review aims to summarize the recent advancements of microneedle patches in application for drugs and vaccine delivery. We reviewed the most of recently published papers on microneedle patches, summarized their evolution, classification, state-of the-art capabilities and discussed promising application in drugs and vaccine delivery. With the rapid development of nanotechnology, microneedle patches have been improved by switching from undissolving to dissolving microneedles, and their safety has also improved dramatically. As a drug delivery tool, microneedle patches can deliver bioactive molecular of different physical size. Additionally, microneedle patches can be coated or encapsulate with DNA vaccine, subunit antigen, inactivated or live virus vaccine. Combining clinical results with the results of patient interview, microneedle patches are found to be feasible and are predicated to soon be acceptable for the medical service. In this review, we summarized the evolution, current and future application of microneedle patches as delivery vehicle for drugs and vaccines. Compared with traditional delivery tools, microneedle patches have many advantages, such as providing pain-free, non-invasive, convenient route for reagent administration and delivery, with no cold chain required for storage and transportation as well as decreasing sharp medical waste, needle-caused injury and transmission of blood-borne infectious disease in rural area. However, even though there are dramatic progress in preclinical investigation of microneedle patches, further testing will be required for clinical application. Further research should be implemented in multiple fields

  1. Microneedles for intradermal and transdermal delivery

    Science.gov (United States)

    Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

    2014-01-01

    The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

  2. The Troy Microneedle: A Rapidly Separating, Dissolving Microneedle Formed by Cyclic Contact and Drying on the Pillar (CCDP.

    Directory of Open Access Journals (Sweden)

    Miroo Kim

    Full Text Available In dissolving microneedle (DMN-mediated therapy, complete and rapid delivery of DMNs is critical for the desired efficacy. Traditional patch-based DMN delivery, however, may fail due to incomplete delivery from insufficient skin insertion or rapid separation of microneedles due to their strong bond to the backing film. Here, we introduce the Troy microneedle, which was created by cyclic contact and drying on the pillar (CCDP, and which enabled simultaneous complete and rapid delivery of DMN. This CCDP process could be flexibly repeated to achieve a specific desired drug dose in a DMN. We evaluated DMN separation using agarose gel, and the Troy microneedle achieved more complete and rapid separation than other, more deeply dipped DMN, primarily because of the Troy's minimal junction between the DMN and pillar. When Troy microneedles were applied to pig cadaver skin, it took only 15 s for over 90% of encapsulated rhodamine B to be delivered, compared to 2 h with application of a traditional DMN patch. In vivo skin penetration studies demonstrated rapid DMN-separation of Troy microneedles still in solid form before dissolution. The Troy microneedle overcomes critical issues associated with the low penetration efficiency of flat patch-based DMN and provides an innovative route for DMN-mediated therapy, combining patient convenience with the desire drug efficacy.

  3. Measles vaccination using a microneedle patch☆

    Science.gov (United States)

    Edens, Chris; Collins, Marcus L.; Ayers, Jessica; Rota, Paul A.; Prausnitz, Mark R.

    2013-01-01

    Measles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. Viability of vaccine virus dried onto a microneedle patch was stabilized by incorporation of the sugar, trehalose, and loss of viral titer was less than 1 log10(TCID50) after storage for at least 30 days at room temperature. Microneedle patches were then used to immunize cotton rats with the Edmonston-Zagreb measles vaccine strain. Vaccination using microneedles at doses equaling the standard human dose or one-fifth the human dose generated neutralizing antibody levels equivalent to those of a subcutaneous immunization at the same dose. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection. PMID:23044406

  4. Microneedle-Mediated Delivery of Copper Peptide Through Skin.

    Science.gov (United States)

    Li, Hairui; Low, Yong Sheng Jason; Chong, Hui Ping; Zin, Melvin T; Lee, Chi-Ying; Li, Bo; Leolukman, Melvina; Kang, Lifeng

    2015-08-01

    Copper peptide (GHK-Cu) plays an important role in skin regeneration and wound healing. However, its skin absorption remains challenging due to its hydrophilicity. Here we use polymeric microneedle array to pre-treat skin to enhance GHK-Cu skin penetration. Two in vitro skin models were used to assess the capability of microneedles in facilitating skin delivery of GHK-Cu. Histological assay and confocal laser scanning microscopy were performed to characterize and quantify the microconduits created by the microneedles inside skin. Cellular and porcine models were used to evaluate the safety of microneedle-assisted copper peptide delivery. The depth and percentage of microneedle penetration were correlated with application forces, which in turn influenced the extent of enhancement in the skin permeability of GHK-Cu. In 9 h, 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated though the microneedle treated human skin, while almost no peptide or copper permeated through intact human skin. No obvious signs of skin irritation were observed with the use of GHK-Cu after microneedle pretreatment. It is effective and safe to enhance the skin permeation of GHK-Cu by using microneedles. This approach may be useful to deliver similar peptides or minerals through skin.

  5. [Development of a Futuristic Microneedle Based on Nanotechnology].

    Science.gov (United States)

    Tsuchiya, Kazuyoshi

    2015-11-01

    The author proposes "the microtube production technique", which is based on "nanotechnology", to produce a microneedle which mimicks a female mosquito's labium to collect blood almost painlessly. The microneedle production technique is to deposit the microneedle material on a rotating wire substrate at a speed of 3-5 rpm by a sputtering deposition method and etch the wire substrate by a chemical solution after a heat treatment As the result, a titanium microneedle was produced (outer and inner diameter: 50 μm and 25 μm) in the same size of female mosquito's labium. In this paper, microtube production technique is introduced first as a key technology. The design technique of painless microneedle for blood extraction system based on quantitative pain assessment, are also proposed to produce solid type microneedle with trenches on the surface of the needle.

  6. Microneedles array with biodegradable tips for transdermal drug delivery

    Science.gov (United States)

    Iliescu, Ciprian; Chen, Bangtao; Wei, Jiashen; Tay, Francis E. H.

    2008-12-01

    The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient manner, at the same time; they are breakable and biodegradable. Basically, the main problem of the silicon microneedles consists of broken microneedles tips during the insertion. The solution proposed is to fabricate the microneedle tip from a biodegradable material - porous silicon. The silicon microneedles are fabricated using DRIE notching effect of reflected charges on mask. The process overcomes the difficulty in the undercut control of the tips during the classical isotropic silicon etching process. When the silicon tips were formed, the porous tips were then generated using a classical electrochemical anodization process in MeCN/HF/H2O solution. The paper presents the experimental results of in vitro release of calcein and BSA with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without any enhancer, the microneedle array had presented significant enhancement of drug release.

  7. Enhanced skin delivery of vismodegib by microneedle treatment.

    Science.gov (United States)

    Nguyen, Hiep X; Banga, Ajay K

    2015-08-01

    The present study investigated the effects of microneedle treatment (maltose microneedles, Admin Pen™ 1200, and Admin Pen™ 1500) on in vitro transdermal delivery of vismodegib with different needle lengths, skin equilibration times, and microneedle insertion durations. The influence of microneedle treatment on the dimensions of microchannels (dye binding, calcein imaging, histology, and confocal microscopy studies), transepidermal water loss, and skin permeability of vismodegib was also evaluated. Skin viscoelasticity was assessed using a rheometer, and microneedle geometry was characterized by scanning electron microscopy. Permeation studies of vismodegib through dermatomed porcine ear skin were conducted using vertical Franz diffusion cells. Skin irritation potential of vismodegib formulation was assessed using an in vitro reconstructed human epidermis model. Results of the in vitro permeation studies revealed significant enhancement in permeation of vismodegib through microneedle-treated skin. As the needle length increased from 500 to 1100 and 1400 μm, drug delivery increased from 14.50 ± 2.35 to 32.38 ± 3.33 and 74.40 ± 15.86 μg/cm(2), respectively. Positive correlation between drug permeability and microneedle treatment duration was observed. The equilibration time was also found to affect the delivery of vismodegib. Thus, changes in microneedle length, equilibration time, and duration of treatment altered transdermal delivery of vismodegib.

  8. Photoacoustic microscopy imaging for microneedle drug delivery

    Science.gov (United States)

    Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

    2018-02-01

    The recent development of novel transdermal drug delivery systems (TDDS) using microneedle technology allows micron-sized conduits to be formed within the outermost skin layers attracting keen interest in skin as an interface for localized and systemic delivery of therapeutics. In light of this, researchers are using microneedles as tools to deliver nanoparticle formulations to targeted sites for effective therapy. However, in such studies the use of traditional histological methods are employed for characterization and do not allow for the in vivo visualization of drug delivery mechanism. Hence, this study presents a novel imaging technology to characterize microneedle based nanoparticle delivery systems using optical resolution-photoacoustic microscopy (OR-PAM). In this study in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and the spatial distribution of the nanoparticles in the tissue was successfully illustrated. Characterization of parameters that are relevant in drug delivery studies such as penetration depth, efficiency of delivered gold nanoparticles were monitored using the system. Photoacoustic microscopy proves an ideal tool for the characterization studies of microneedle properties and the studies shows microneedles as an ideal tool for precise and controlled drug delivery.

  9. Deposition of antimicrobial coatings on microstereolithography-fabricated microneedles

    Science.gov (United States)

    Gittard, Shaun D.; Miller, Philip R.; Jin, Chunming; Martin, Timothy N.; Boehm, Ryan D.; Chisholm, Bret J.; Stafslien, Shane J.; Daniels, Justin W.; Cilz, Nicholas; Monteiro-Riviere, Nancy A.; Nasir, Adnan; Narayan, Roger J.

    2011-06-01

    Microneedles are small-scale needle-like projections that may be used for transdermal delivery of pharmacologic agents, including protein-containing and nucleic acid-containing agents. Commercial translation of polymeric microneedles would benefit from the use of facile and cost effective fabrication methods. In this study, visible light dynamic mask microstereolithography, a rapid prototyping technique that utilizes digital light projection for selective polymerization of a liquid resin, was used for fabrication of solid microneedle array structures out of an acrylate-based polymer. Pulsed laser deposition was used to deposit silver and zinc oxide coatings on the surfaces of the visible light dynamic mask microstereolithography-fabricated microneedle array structures. Agar diffusion studies were used to demonstrate the antimicrobial activity of the coated microneedle array structures. This study indicates that light-based technologies, including visible light dynamic mask microstereolithography and pulsed laser deposition, may be used to fabricate microneedles with antimicrobial properties for treatment of local skin infections.

  10. A scalable fabrication process of polymer microneedles

    Directory of Open Access Journals (Sweden)

    Yang S

    2012-03-01

    Full Text Available Sixing Yang, Yan Feng, Lijun Zhang, Nixiang Chen, Weien Yuan, Tuo JinSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaAbstract: While polymer microneedles may easily be fabricated by casting a solution in a mold, either centrifugation or vacuumizing is needed to pull the viscous polymer solution into the microholes of the mold. We report a novel process to fabricate polymer microneedles with a one-sided vacuum using a ceramic mold that is breathable but water impermeable. A polymer solution containing polyvinyl alcohol and polysaccharide was cast in a ceramic mold and then pulled into the microholes by a vacuum applied to the opposite side of the mold. After cross-linking and solidification through freeze-thawing, the microneedle patch was detached from the mold and transferred with a specially designed instrument for the drying process, during which the patch shrank evenly to form an array of regular and uniform needles without deformation. Moreover, the shrinkage of the patches helped to reduce the needles' size to ease microfabrication of the male mold. The dried microneedle patches were finally punched to the desired sizes to achieve various properties, including sufficient strength to penetrate skin, microneedles-absorbed water-swelling ratios, and drug-release kinetics. The results showed that the microneedles were strong enough to penetrate pigskin and that their performance was satisfactory in terms of swelling and drug release.Keywords: polymer microneedles, ceramic mold, polyvinyl alcohol, swelling

  11. Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles

    Science.gov (United States)

    Cha, Kyoung Je; Kim, Taewan; Jea Park, Sung; Kim, Dong Sung

    2014-11-01

    Polymer microneedle arrays (MNAs) have received much attention for their use in transdermal drug delivery and microneedle therapy systems due to the advantages they offer, such as low cost, good mechanical properties, and a versatile choice of materials. Here, we present a simple and cost-effective method for the fabrication of a biodegradable polymer MNA in which the aspect ratio of each microneedle is adjustable using commercially available acupuncture microneedles. In our process, a master template with acupuncture microneedles, whose shape will be the final MNA, was carefully prepared by fixing them onto a plastic substrate with selectively drilled holes which, in turn, determine the aspect ratios of the microneedles. A polylactic acid (PLA; a biodegradable polymer) MNA was fabricated by a micromolding process with a polydimethylsiloxane (PDMS) mold containing the cavity of the microneedles, which was obtained by the PDMS replica molding against the master template. The mechanical force and degradation behavior of the replicated PLA MNA were characterized with the help of a compression test and an accelerated degradation test, respectively. Finally, the transdermal drug delivery performance of the PLA MNA was successfully simulated by two different methods of penetration and staining, using the skin of a pig cadaver. These results indicated that the proposed method can be effectively used for the fabrication of polymer MNAs which can be used in various microneedle applications.

  12. Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles

    International Nuclear Information System (INIS)

    Cha, Kyoung Je; Kim, Taewan; Park, Sung Jea; Kim, Dong Sung

    2014-01-01

    Polymer microneedle arrays (MNAs) have received much attention for their use in transdermal drug delivery and microneedle therapy systems due to the advantages they offer, such as low cost, good mechanical properties, and a versatile choice of materials. Here, we present a simple and cost-effective method for the fabrication of a biodegradable polymer MNA in which the aspect ratio of each microneedle is adjustable using commercially available acupuncture microneedles. In our process, a master template with acupuncture microneedles, whose shape will be the final MNA, was carefully prepared by fixing them onto a plastic substrate with selectively drilled holes which, in turn, determine the aspect ratios of the microneedles. A polylactic acid (PLA; a biodegradable polymer) MNA was fabricated by a micromolding process with a polydimethylsiloxane (PDMS) mold containing the cavity of the microneedles, which was obtained by the PDMS replica molding against the master template. The mechanical force and degradation behavior of the replicated PLA MNA were characterized with the help of a compression test and an accelerated degradation test, respectively. Finally, the transdermal drug delivery performance of the PLA MNA was successfully simulated by two different methods of penetration and staining, using the skin of a pig cadaver. These results indicated that the proposed method can be effectively used for the fabrication of polymer MNAs which can be used in various microneedle applications. (paper)

  13. Anti-arthritic effects of microneedling with bee venom gel

    OpenAIRE

    Mengdi Zhao; Jie Bai; Yang Lu; Shouying Du; Kexin Shang; Pengyue Li; Liu Yang; Boyu Dong; Ning Tan

    2016-01-01

    Objective: To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel. Methods: In this study, the sodium urate and LPS were used on rats and mice to construct the model. Bee venom gel–microneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors. Results: Compared with the model group, the bee venom gel–microneedle combination group can r...

  14. Microneedle physical contact as a therapeutic for abnormal scars.

    Science.gov (United States)

    Yeo, David C; Balmayor, Elizabeth R; Schantz, Jan-Thorsten; Xu, Chenjie

    2017-08-14

    Abnormal (keloid and hypertrophic) scars are a significant affliction with no satisfactory single modality therapy to-date. Available options are often ineffective, painful, potentially hazardous, and require healthcare personnel involvement. Herein a self-administered microneedle device based on drug-free physical contact for inhibiting abnormal scars is reported. Its therapeutic activity through microneedle contact eliminates hazards associated with toxic anti-scarring drugs while self-treatment enables administration flexibility. The microneedle patch was fabricated with FDA-approved liquid crystalline polymer under good manufacturing practice. It was first tested to ascertain its ability to inhibit (keloid) fibroblast proliferation. Later the microneedle patch was examined on the rabbit ear hypertrophic scar model to explore its potential in inhibiting the generation of abnormal scars post-injury. Finally, the microneedle patch was applied to the caudal region of a hypertrophic scar located on a female patient's dorsum to verify clinical efficacy. On untreated control cultures, barely any non-viable fibroblasts could be seen. After 12-h treatment with the microneedle patch, the non-viable proportion increased to 83.8 ± 11.96%. In rabbit ear hypertrophic scar model, 100% of the control wounds without the presence of patches on rabbit ears generated regions of raised dermis originating from the wound site (3/3), whereas microneedle treatment prevented dermis tissue thickening in 83.33% of the wounds (15/18). In the clinical test, the microneedle patch was well tolerated by the patient. Compared to the untreated region, microneedle treatment decreased the number of infiltrated inflammatory cells, with less disrupted dermis tissue architecture and more flattened appearance. A self-administered, drug-free microneedle patch appears highly promising in reducing abnormal scarring as observed from in vitro, in vivo and clinical experiments. Larger cohort clinical

  15. Safety evaluation of stamp type digital microneedle devices in hairless mice.

    Science.gov (United States)

    Park, Kui Young; Jang, Woo Sun; Lim, Yun Young; Ahn, Joo Hee; Lee, Sang Jin; Kim, Chan Woong; Kim, Sung Eun; Kim, Beom Joon; Kim, Myeung Nam

    2013-02-01

    Microneedles provide a minimally invasive means to transport molecules into the skin. A number of specific strategies have been employed to use microneedles for transdermal delivery. The purpose of this study was to investigate the safety of two new digital microneedle devices (Digital Hand® and Digital Pro®; Bomtech Electronics Co., Ltd., Seoul, Korea) for the perforation of skin in skin-hairless-1 mice. This device replaces conventional needles and is designed specifically for intradermal delivery. We used two newly developed digital microneedle devices to perforate the skin of skin-hairless-1 mice. We conducted a comparative study of the two digital microneedle devices and DTS® (Disk type-microneedle Therapy System; DTS lab., Seoul, Korea). To evaluate skin stability, we performed visual and dermatoscopic inspections, measurements of transepidermal water loss, and biopsies. The two novel digital microneedle devices did not induce significant abnormalities of the skin on visual or dermatoscopic inspection, regardless of needle size (0.25~2.0 mm). No significant histopathological changes, such as inflammatory cell infiltration, desquamation of the stratum corneum, or disruption of the basal layer, were observed. The digital microneedle devices and microneedle therapy system produced similar results on measures of skin stability. These two novel digital microneedle devices are safe transdermal drug delivery systems.

  16. Diclofenac enables prolonged delivery of naltrexone through microneedle-treated skin.

    Science.gov (United States)

    Banks, Stan L; Paudel, Kalpana S; Brogden, Nicole K; Loftin, Charles D; Stinchcomb, Audra L

    2011-05-01

    The purpose of this study was to determine if non-specific COX inhibition could extend pore lifetime in hairless guinea pigs following microneedle treatment. Hairless guinea pigs were treated with microneedle arrays ± daily application of Solaraze® gel (3% diclofenac sodium (non-specific COX inhibitor) and 2.5% hyaluronic acid); transepidermal water loss was utilized to evaluate pore lifetime. To examine the permeation of naltrexone, additional guinea pigs were treated with microneedles ± daily Solaraze® gel followed by application of a 16% transdermal naltrexone patch; pharmacokinetic analysis of plasma naltrexone levels was performed. Histological analysis was employed to visualize morphological changes following microneedle and Solaraze® treatment. Animals treated with microneedles + Solaraze® displayed extended pore lifetime (determined by transepidermal water loss measurements) for up to 7 days. Enhanced naltrexone permeation was also observed for an extended amount of time in animals treated with microneedles + Solaraze®. No morphological changes resulting from microneedle treatment or COX inhibition were noted. Non-specific COX inhibition is an effective means of extending pore lifetime following microneedle treatment in hairless guinea pigs. This may have clinical implications for extending transdermal patch wear time and therefore increasing patient compliance with therapy.

  17. An update on coating/manufacturing techniques of microneedles.

    Science.gov (United States)

    Tarbox, Tamara N; Watts, Alan B; Cui, Zhengrong; Williams, Robert O

    2017-12-29

    Recently, results have been published for the first successful phase I human clinical trial investigating the use of dissolving polymeric microneedles… Even so, further clinical development represents an important hurdle that remains in the translation of microneedle technology to approved products. Specifically, the potential for accumulation of polymer within the skin upon repeated application of dissolving and coated microneedles, combined with a lack of safety data in humans, predicates a need for further clinical investigation. Polymers are an important consideration for microneedle technology-from both manufacturing and drug delivery perspectives. The use of polymers enables a tunable delivery strategy, but the scalability of conventional manufacturing techniques could arguably benefit from further optimization. Micromolding has been suggested in the literature as a commercially viable means to mass production of both dissolving and swellable microneedles. However, the reliance on master molds, which are commonly manufactured using resource intensive microelectronics industry-derived processes, imparts notable material and design limitations. Further, the inherently multi-step filling and handling processes associated with micromolding are typically batch processes, which can be challenging to scale up. Similarly, conventional microneedle coating processes often follow step-wise batch processing. Recent developments in microneedle coating and manufacturing techniques are highlighted, including micromilling, atomized spraying, inkjet printing, drawing lithography, droplet-born air blowing, electro-drawing, continuous liquid interface production, 3D printing, and polyelectrolyte multilayer coating. This review provides an analysis of papers reporting on potentially scalable production techniques for the coating and manufacturing of microneedles.

  18. Microneedle, microneedle array and production method therefor

    NARCIS (Netherlands)

    Berenschot, Johan W.; Wissink, Jeroen Mathijn; Tas, Niels Roelof; de Boer, Meint J.

    2009-01-01

    The present invention provides a microneedle, comprising a shaft of a monocrystalline material having at least three walls which are formed by a crystal plane of the monocrystalline material; and a tip connected to an end of the shaft comprising at least three walls which are formed by a crystal

  19. Microneedle, microneedle array and production method therefor

    NARCIS (Netherlands)

    Berenschot, Johan W.; Wissink, Jeroen Mathijn; Tas, Niels Roelof; de Boer, Meint J.

    2008-01-01

    The present invention provides a microneedle, comprising a shaft of a monocrystalline material having at least three walls which are formed by a crystal plane of the monocrystalline material; and a tip connected to an end of the shaft comprising at least three walls which are formed by a crystal

  20. Microneedle Array Interface to CE on Chip

    NARCIS (Netherlands)

    Lüttge, Regina; Gardeniers, Johannes G.E.; Vrouwe, E.X.; van den Berg, Albert; Northrup, M.A.; Jensen, K.F; Harrison, D.J.

    2003-01-01

    This paper presents a microneedle array sampler interfaced to a capillary electrophoresis (CE) glass chip with integrated conductivity detection electrodes. A solution of alkali ions was electrokinetically loaded through the microneedles onto the chip and separation was demonstrated compared to a

  1. Transdermal microneedles for drug delivery applications

    International Nuclear Information System (INIS)

    Teo, Ai Ling; Shearwood, Christopher; Ng, Kian Chye; Lu Jia; Moochhala, Shabbir

    2006-01-01

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area

  2. Transdermal microneedles for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Ai Ling [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Shearwood, Christopher [School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, Kian Chye [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Lu Jia [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore)]. E-mail: mshabbir@dso.org.sg

    2006-07-25

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area.

  3. Repeated Microneedle Stimulation Induces Enhanced Hair Growth in a Murine Model.

    Science.gov (United States)

    Kim, Yoon Seob; Jeong, Kwan Ho; Kim, Jung Eun; Woo, Young Jun; Kim, Beom Joon; Kang, Hoon

    2016-10-01

    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. 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. 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. 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. 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.

  4. Microneedle Manufacture: Assessing Hazards and Control Measures

    Directory of Open Access Journals (Sweden)

    Alexander Martin

    2017-10-01

    Full Text Available Transdermal microneedles have captured the attention of researchers in relation to a variety of applications, and silicone-based moulds required to produce these systems are now widely available and can be readily manufactured on the lab bench. There is however some concern over the potential for accidental needlestick injuries and, as with any sharp hazard, the potential for blood-borne pathogen transmission must be considered. This follows from recent governmental concerns over the use of microneedle systems in dermabrasion. Despite the piercing nature of the microneedle patch sharing many similarities with conventional hypodermic needles, there are notable factors that mitigate the risk of contamination. A range of microneedle systems has been prepared using micromoulding techniques, and their puncture capability assessed. A critical assessment of the potential for accidental puncture and the control measures needed to ensure safe utilisation of the patch systems is presented.

  5. Pulsed laser deposition of antimicrobial silver coating on Ormocer (registered) microneedles

    Energy Technology Data Exchange (ETDEWEB)

    Gittard, S D; Narayan, R J; Jin, C; Monteiro-Riviere, N A [Joint Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695 (United States); Ovsianikov, A; Chichkov, B N [Laser Zentrum Hannover, Hollerithallee 8, 30419 Hannover (Germany); Stafslien, S; Chisholm, B, E-mail: roger_narayan@msn.co [Center for Nanoscale Science and Engineering, North Dakota State University, 1805 Research Park Drive, Fargo, ND 58102 (United States)

    2009-12-15

    One promising option for transdermal delivery of protein- and nucleic acid-based pharmacologic agents involves the use of microneedles. However, microneedle-generated pores may allow microorganisms to penetrate the stratum corneum layer of the epidermis and cause local or systemic infection. In this study, microneedles with antimicrobial functionality were fabricated using two-photon polymerization-micromolding and pulsed laser deposition. The antibacterial activity of the silver-coated organically modified ceramic (Ormocer (registered) ) microneedles was demonstrated using an agar diffusion assay. Human epidermal keratinocyte viability on the Ormocer (registered) surfaces coated with silver was similar to that on uncoated Ormocer (registered) surfaces. This study indicates that coating microneedles with silver thin films using pulsed laser deposition is a useful and novel approach for creating microneedles with antimicrobial functionality. (communication)

  6. Pulsed laser deposition of antimicrobial silver coating on Ormocer (registered) microneedles

    International Nuclear Information System (INIS)

    Gittard, S D; Narayan, R J; Jin, C; Monteiro-Riviere, N A; Ovsianikov, A; Chichkov, B N; Stafslien, S; Chisholm, B

    2009-01-01

    One promising option for transdermal delivery of protein- and nucleic acid-based pharmacologic agents involves the use of microneedles. However, microneedle-generated pores may allow microorganisms to penetrate the stratum corneum layer of the epidermis and cause local or systemic infection. In this study, microneedles with antimicrobial functionality were fabricated using two-photon polymerization-micromolding and pulsed laser deposition. The antibacterial activity of the silver-coated organically modified ceramic (Ormocer (registered) ) microneedles was demonstrated using an agar diffusion assay. Human epidermal keratinocyte viability on the Ormocer (registered) surfaces coated with silver was similar to that on uncoated Ormocer (registered) surfaces. This study indicates that coating microneedles with silver thin films using pulsed laser deposition is a useful and novel approach for creating microneedles with antimicrobial functionality. (communication)

  7. Microfabricated microneedle with porous tip for drug delivery

    Science.gov (United States)

    Ji, Jing; Tay, Francis E. H.; Miao, Jianmin; Iliescu, Ciprian

    2006-05-01

    This paper presents a novel approach to fabrication of a silicon microneedle array with porous tips. Dry etching technology with SF6/O2 gas by STS's inductively coupled plasma (ICP) etch tool was used to achieve the pyramidal needle structure. A thin silicon nitride layer was deposited after a thick photoresist layer was coated and reflowed at 120 °C. The silicon nitride layer and residual photoresist on the tips of the pyramidal structures were removed using reactive ion etching (RIE). Electrochemical etching in MeCN/HF was carried out to generate porous silicon on the tips of the microneedles. The fabricated microneedle array has potential applications in drug delivery, since the porous tips can be loaded with a high molecular weight drug. Analytic solutions to the critical loadings of the fabricated microneedle structure are also presented. The variations of the square cross-section were expressed as a function of the axial coordinate to analyze the bending normal stress and critical buckling loading. This analytic method can also be used for other microneedle structures with different cross-sections.

  8. Spatially discrete thermal drawing of biodegradable microneedles for vascular drug delivery.

    Science.gov (United States)

    Choi, Chang Kuk; Lee, Kang Ju; Youn, Young Nam; Jang, Eui Hwa; Kim, Woong; Min, Byung-Kwon; Ryu, WonHyoung

    2013-02-01

    Spatially discrete thermal drawing is introduced as a novel method for the fabrication of biodegradable microneedles with ultra-sharp tip ends. This method provides the enhanced control of microneedle shapes by spatially controlling the temperature of drawn polymer as well as drawing steps and speeds. Particular focus is given on the formation of sharp tip ends of microneedles at the end of thermal drawing. Previous works relied on the fracture of polymer neck by fast drawing that often causes uncontrolled shapes of microneedle tips. Instead, this approach utilizes the surface energy of heated polymer to form ultra-sharp tip ends. We have investigated the effect of such temperature control, drawing speed, and drawing steps in thermal drawing process on the final shape of microneedles using biodegradable polymers. XRD analysis was performed to analyze the effect of thermal cycle on the biodegradable polymer. Load-displacement measurement also showed the dependency of mechanical strengths of microneedles on the microneedle shapes. Ex vivo vascular tissue insertion and drug delivery demonstrated microneedle insertion to tunica media layer of canine aorta and drug distribution in the tissue layer. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Prestrain-induced Reduction in Skin Tissue Puncture Force of Microneedle

    International Nuclear Information System (INIS)

    Kim, Jonghun; Park, Sungmin; Nam, Gyungmok; Yoon, Sang-Hee

    2016-01-01

    Despite all the recent advances in biodegradable material-based microneedles, the bending and failure (especially buckling) of a biodegradable microneedle during skin tissue insertion remains a major technical hurdle for its large-scale commercialization. A reduction in skin tissue puncture force during microneedle insertion remains an essential issue in successfully developing a biodegradable microneedle. Here, we consider uniaxial and equibiaxial prestrains applied to a skin tissue as mechanophysical stimuli that can reduce the skin tissue puncture force, and investigate the effect of prestrain on the changes in skin tissue puncture force. For a porcine skin tissue similar to that of humans, the skin tissue puncture force of a flat-end microneedle is measured with a z-axis stage equipped with a load cell, which provides a force-time curve during microneedle insertion. The findings of this study lead to a quantitative characterization of the relationship between prestrain and the skin tissue puncture force

  10. Prestrain-induced Reduction in Skin Tissue Puncture Force of Microneedle

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jonghun; Park, Sungmin; Nam, Gyungmok; Yoon, Sang-Hee [Inha Univ., Incheon (Korea, Republic of)

    2016-10-15

    Despite all the recent advances in biodegradable material-based microneedles, the bending and failure (especially buckling) of a biodegradable microneedle during skin tissue insertion remains a major technical hurdle for its large-scale commercialization. A reduction in skin tissue puncture force during microneedle insertion remains an essential issue in successfully developing a biodegradable microneedle. Here, we consider uniaxial and equibiaxial prestrains applied to a skin tissue as mechanophysical stimuli that can reduce the skin tissue puncture force, and investigate the effect of prestrain on the changes in skin tissue puncture force. For a porcine skin tissue similar to that of humans, the skin tissue puncture force of a flat-end microneedle is measured with a z-axis stage equipped with a load cell, which provides a force-time curve during microneedle insertion. The findings of this study lead to a quantitative characterization of the relationship between prestrain and the skin tissue puncture force.

  11. Microneedles from Fishscale-Nanocellulose Blends Using Low Temperature Mechanical Press Method

    OpenAIRE

    Olatunji, Ololade; Olsson, Richard T.

    2015-01-01

    Fish scale biopolymer blended with nanocellulose crystals is used for production of microneedles applying mechanical press microfabrication and the effect of nanocellulose on microfabrication, water absorption, moisture stability and mechanical properties of the microneedles is reported. The results show that microneedles produced from the nanocellulose loaded fish scale biopolymer requires higher temperature for micromolding (80 ± 5 °C) than microneedles from only fish scale biopolymer, whi...

  12. In Vitro Skin Permeation Enhancement of Sumatriptan by Microneedle Application.

    Science.gov (United States)

    Nalluri, Buchi N; Anusha, Sai Sri V; Bramhini, Sri R; Amulya, J; Sultana, Ashraf S K; Teja, Chandra U; Das, Diganta B

    2015-01-01

    Different dimensions of commercially available microneedle devices, namely, Admin- Patch(®) microneedle arrays (MN) (0.6, 0.9, 1.2 and 1.5 mm lengths) and Dermaroller(®) microneedle rollers (DR) (0.5 and 1mm lengths) were evaluated for their relative efficiency in enhancement of transdermal permeation of Sumatriptan (SMT). Solubility assessment of SMT was carried out using propylene glycol (PG), polyethylene glycol (PEG) in combination with saline (S) at different ratios and the order of solubility was found to be 70:30 > 80:20 > 90:10 %v/v in both PG:S and PEG:S. In vitro skin permeation studies were performed using PG:S (70:30 %v/v) as donor vehicle. A significant increase in cumulative amount of SMT permeated, steady state flux, permeability coefficient and diffusion coefficient values were observed after microneedle treatment, and the values were in the order of 1.5mm MN >1.2mm MN >0.9mm MN >1mm DR >0.6mm MN >0.5mm DR > passive permeation. Lag times were significantly shorter after longer microneedle application (0.24h for 1.5mm MN). Arrays were found to be superior to rollers with similar microneedle lengths in enhancing SMT permeation and may be attributed to higher density of microneedles and force of application onto skin. The in vitro flux values revealed that 2.5cm(2) area patch is sufficient for effective therapy after treatment of skin with 1.5mm MN. It may be inferred that microneedle application significantly enhances the transdermal penetration of SMT and that it may be feasible to deliver clinically relevant therapeutic levels of SMT using microneedle assisted transdermal delivery systems.

  13. Post-closure permit application for the Kerr Hollow Quarry at the Y-12 plant

    International Nuclear Information System (INIS)

    1995-06-01

    The Kerr Hollow Quarry (KHQ) is located on U.S. Department of Energy (DOE) property at the Y-12 Plant, Oak Ridge, Tennessee. The Oak Ridge Y-12 Plant was built by the U.S. Army Corps of Engineers in 1943 as part of the Manhattan Project. Until 1992, the primary mission of the Y-12 Plant was the production and fabrication of nuclear weapons components. Activities associated with these functions included production of lithium compounds, recovery of enriched uranium from scrap material, and fabrication of uranium and other materials into finished parts for assemblies. The Kerr Hollow Quarry was used for waste disposal of a variety of materials including water-reactive and shock-sensitive chemicals and compressed gas cylinders. These materials were packaged in various containers and sank under the water in the quarry due to their great weight. Disposal activities were terminated in November, 1988 due to a determination by the Tennessee Department of Environment and Conservation that the quarry was subject to regulations under the Resource Conservation and Recovery Act of 1993. Methods of closure for the quarry were reviewed, and actions were initiated to close the quarry in accordance with closure requirements for interim status surface impoundments specified in Tennessee Rules 1200-1-11-.05(7) and 1200-1-11-.05(11). As part of these actions, efforts were made to characterize the physical and chemical nature of wastes that had been disposed of in the quarry, and to remove any containers or debris that were put into the quarry during waste disposal activities. Closure certification reports (Fraser et al. 1993 and Dames and Moore 1993) document closure activities in detail. This report contains the post-closure permit application for the Kerr Hollow Quarry site

  14. A novel fabrication process for out-of-plane microneedle sheets of biocompatible polymer

    Science.gov (United States)

    Han, Manhee; Hyun, Dong-Hun; Park, Hyoun-Hyang; Lee, Seung S.; Kim, Chang-Hyeon; Kim, Changgyou

    2007-06-01

    This paper presents a novel process for fabricating out-of-plane microneedle sheets of biocompatible polymer using in-plane microneedles. This process comprises four steps: (1) fabrication of in-plane microneedles using inclined UV lithography and electroforming, (2) conversion of the in-plane microneedles to an out-of-plane microneedle array, (3) fabrication of a negative PDMS mold and (4) fabrication of out-of-plane microneedle sheets of biocompatible polymer by hot embossing. The in-plane microneedles are fabricated with a sharp tip for low insertion forces and are made long to ensure sufficient penetration depth. The in-plane microneedles are converted into an out-of-plane microneedle array to increase the needle density. The negative mold is fabricated for mass-production using a polymer molding technique. The final out-of-plane microneedle sheets are produced using polycarbonate for biocompatibility by employing the hot embossing process. The height of the fabricated needles ranges from 500 to 1500 µm, and the distance between the needles is 500 to 2000 µm. The radii of curvature are approximately 2 µm, while the tip angles are in the range of 39-56°. Most of the geometrical characteristics of the out-of-plane microneedles can be freely controlled for real life applications such as drug delivery, cosmetic delivery and mesotherapy. Since it is also possible to mass-produce the microneedles, this novel process holds sufficient potential for applications in industrial fields.

  15. Continuous minimally-invasive alcohol monitoring using microneedle sensor arrays.

    Science.gov (United States)

    Mohan, A M Vinu; Windmiller, Joshua Ray; Mishra, Rupesh K; Wang, Joseph

    2017-05-15

    The present work describes an attractive skin-worn microneedle sensing device for the minimally invasive electrochemical monitoring of subcutaneous alcohol. The device consists of an assembly of pyramidal microneedle structures integrated with Pt and Ag wires, each with a microcavity opening. The microneedle aperture was modified by electropolymerizing o-phenylene diamine onto the Pt wire microtransducer, followed by the immobilization of alcohol oxidase (AOx) in an intermediate chitosan layer, along with an outer Nafion layer. The resulting microneedle-based enzyme electrode displays an interference-free ethanol detection in artificial interstitial fluid without compromising its sensitivity, stability and response time. The skin penetration ability and the efficaciousness of the biosensor performance towards subcutaneous alcohol monitoring was substantiated by the ex vivo mice skin model analysis. Our results reveal that the new microneedle sensor holds considerable promise for continuous non-invasive alcohol monitoring in real-life situations. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Continuous minimally-invasive alcohol monitoring using microneedle sensor arrays

    OpenAIRE

    Mohan, AMV; Windmiller, JR; Mishra, RK; Wang, J

    2017-01-01

    The present work describes an attractive skin-worn microneedle sensing device for the minimally invasive electrochemical monitoring of subcutaneous alcohol. The device consists of an assembly of pyramidal microneedle structures integrated with Pt and Ag wires, each with a microcavity opening. The microneedle aperture was modified by electropolymerizing o-phenylene diamine onto the Pt wire microtransducer, followed by the immobilization of alcohol oxidase (AOx) in an intermediate chitosan laye...

  17. Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects.

    Science.gov (United States)

    Arya, Jaya; Henry, Sebastien; Kalluri, Haripriya; McAllister, Devin V; Pewin, Winston P; Prausnitz, Mark R

    2017-06-01

    To support translation of microneedle patches from pre-clinical development into clinical trials, this study examined the effect of microneedle patch application on local skin reactions, reliability of use and acceptability to patients. Placebo patches containing dissolving microneedles were administered to fifteen human participants. Microneedle patches were well tolerated in the skin with no pain or swelling and only mild erythema localized to the site of patch administration that resolved fully within seven days. Microneedle patches could be administered by hand without the need of an applicator and delivery efficiencies were similar for investigator-administration and self-administration. Microneedle patch administration was not considered painful and the large majority of subjects were somewhat or fully confident that they self-administered patches correctly. Microneedle patches were overwhelmingly preferred over conventional needle and syringe injection. Altogether, these results demonstrate that dissolving microneedle patches were well tolerated, easily usable and strongly accepted by human subjects, which will facilitate further clinical translation of this technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. A Photolithographic Approach to Polymeric Microneedles Array Fabrication

    Directory of Open Access Journals (Sweden)

    Principia Dardano

    2015-12-01

    Full Text Available In this work, two procedures for fabrication of polymeric microneedles based on direct photolithography, without any etching or molding process, are reported. Polyethylene glycol (average molecular weight 250 Da, casted into a silicone vessel and exposed to ultraviolet light (365 nm through a mask, cross-links when added by a commercial photocatalyzer. By changing the position of the microneedles support with respect to the vessel, different shapes and lengths can be achieved. Microneedles from a hundred microns up to two millimeters have been obtained just tuning the radiation dose, by changing the exposure time (5–15 s and/or the power density (9–18 mW/cm2 during photolithography. Different microneedle shapes, such as cylindrical, conic or lancet-like, for specific applications such as micro-indentation or drug delivery, are demonstrated.

  19. Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery.

    Science.gov (United States)

    Song, Hyun Beom; Lee, Kang Ju; Seo, Il Ho; Lee, Ji Yong; Lee, Sang-Mok; Kim, Jin Hyoung; Kim, Jeong Hun; Ryu, WonHyoung

    2015-07-10

    It has been challenging for microneedles to deliver drugs effectively to thin tissues with little background support such as the cornea. Herein, we designed a microneedle pen system, a single microneedle with a spring-loaded microneedle applicator to provide impact insertion. To firmly attach solid microneedles with 140 μm in height at the end of macro-scale applicators, a transfer molding process was employed. The fabricated microneedle pens were then applied to mouse corneas. The microneedle pens successfully delivered rhodamine dye deep enough to reach the stromal layer of the cornea with small entry only about 1000 μm(2). When compared with syringes or 30 G needle tips, microneedle pens could achieve more localized and minimally invasive delivery without any chances of perforation. To investigate the efficacy of microneedle pens as a way of drug delivery, sunitinib malate proven to inhibit in vitro angiogenesis, was delivered to suture-induced angiogenesis model. When compared with delivery by a 30 G needle tip dipped with sunitinib malate, only delivery by microneedle pens could effectively inhibit corneal neovascularization in vivo. Microneedle pens could effectively deliver drugs to thin tissues without impairing merits of using microneedles: localized and minimally invasive delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Dissolving Microneedle Patch for Transdermal Delivery of Human Growth Hormone

    Science.gov (United States)

    Lee, Jeong Woo; Choi, Seong-O; Felner, Eric I.

    2014-01-01

    Clinical impact of biotechnology has been constrained by the limitations of traditional hypodermic injection of biopharmaceuticals. Microneedle patches have been proposed as a minimally invasive alternative. In this study, we assess the translation of a dissolving microneedle patch designed for simple, painless self-administration of biopharmacetucials that generates no sharp biohazardous waste. To study pharmacokinetics and safety of this approach, human growth hormone (hGH) was encapsulated in 600 μm long dissolving microneedles composed of carboxymethylcellulose and trehalose using an aqueous, moderate-temperature process that maintained complete hGH activity after encapsulation and retained most activity after storage for up to 15 months at room temperature and humidity. After manual insertion into the skin of hairless rats, hGH pharmacokinetics were similar to conventional subcutaneous injection. After patch removal, the microneedles had almost completely dissolved, leaving behind only blunt stubs. The dissolving microneedle patch was well tolerated, causing only slight, transient erythema. This study suggests that a dissolving microneedle patch can deliver hGH and other biopharmaceuticals in a manner suitable for self-administration without sharp biohazardous waste. PMID:21360810

  1. Microneedles: quick and easy delivery methods of vaccines

    Science.gov (United States)

    2017-01-01

    Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route. PMID:28775980

  2. Rabies vaccination in dogs using a dissolving microneedle patch.

    Science.gov (United States)

    Arya, Jaya M; Dewitt, Kristopher; Scott-Garrard, Maya; Chiang, Yu-Wei; Prausnitz, Mark R

    2016-10-10

    Because humans get rabies primarily through dog bites, stray dog population control and mass or mandatory vaccination of domestic dogs and other animals has virtually eliminated human rabies in industrialized countries. However, thousands of people in developing countries die of rabies each year due to the inability to control dog populations and implement mass vaccination because of financial, logistical and other challenges. The availability of an easier-to-administer and more cost-effective vaccine may help to address some of these issues. Here, we propose the use of dissolving microneedle patches for simple and potentially cost-effective rabies vaccination, and assess the safety and immunogenicity of microneedle patch vaccination using a rabies DNA vaccine in dogs. The vaccine was stable upon formulation and storage for at least 3weeks at 4°C in a microneedle patch. For vaccination, the patches were applied to the inner ear by hand without an applicator. Microneedle patches were well tolerated in the skin, with mild erythema, minimal wheal formation and complete resolution of skin reactions within 7days, and generated no systemic adverse events. Microneedle patches were at least as immunogenic as intramuscular injection at the same dose, as demonstrated by similar serum neutralizing antibody titers. A ten-fold lower vaccine dose administered by microneedle patch generated a weaker immune response compared to full-dose intramuscular vaccination. We conclude that dissolving microneedle patches may provide an innovative approach to mass vaccination of dogs. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A Three-Dimensional Enormous Surface Area Aluminum Microneedle Array with Nanoporous Structure

    Directory of Open Access Journals (Sweden)

    Po Chun Chen

    2013-01-01

    Full Text Available We proposed fabricating an aluminum microneedle array with a nanochannel structure on the surface by combining micromachining, electrolyte polishing, and anodization methods. The microneedle array provides a three-dimensional (3D structure that possesses several hundred times more surface area than a traditional nanochannel template. Therefore, the microneedle array can potentially be used in many technology applications. This 3D microneedle array device can not only be used for painless injection or extraction, but also for storage, highly sensitive detection, drug delivery, and microelectrodes. From the calculation we made, the microneedle array not only increases surface area, but also enlarges the capacity of the device. Therefore, the microneedle array can further be used on many detecting, storing, or drug delivering applications.

  4. In-vivo dynamic characterization of microneedle skin penetration using optical coherence tomography

    Science.gov (United States)

    Enfield, Joey; O'Connell, Marie-Louise; Lawlor, Kate; Jonathan, Enock; O'Mahony, Conor; Leahy, Martin

    2010-07-01

    The use of microneedles as a method of circumventing the barrier properties of the stratum corneum is receiving much attention. Although skin disruption technologies and subsequent transdermal diffusion rates are being extensively studied, no accurate data on depth and closure kinetics of microneedle-induced skin pores are available, primarily due to the cumbersome techniques currently required for skin analysis. We report on the first use of optical coherence tomography technology to image microneedle penetration in real time and in vivo. We show that optical coherence tomography (OCT) can be used to painlessly measure stratum corneum and epidermis thickness, as well as microneedle penetration depth after microneedle insertion. Since OCT is a real-time, in-vivo, nondestructive technique, we also analyze skin healing characteristics and present quantitative data on micropore closure rate. Two locations (the volar forearm and dorsal aspect of the fingertip) have been assessed as suitable candidates for microneedle administration. The results illustrate the applicability of OCT analysis as a tool for microneedle-related skin characterization.

  5. Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate.

    Science.gov (United States)

    Kaur, Monika; Ita, Kevin B; Popova, Inna E; Parikh, Sanjai J; Bair, Daniel A

    2014-02-01

    The aim of this project was to study the effect of stainless steel solid microneedles and microneedle rollers on percutaneous penetration of verapamil hydrochloride and amlodipine besylate. Verapamil, 2-(3,4-dimethooxyphenyl)-5-[2-(3,4 dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile is a calcium channel blocker agent that regulates high blood pressure by decreasing myocardial contractilty, heart rate and impulse conduction. Amlodipine, (R, S)-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyridine, is a calcium channel blocker that is used for the management of hypertension and ischemic heart disease. Passive penetration of verapamil and amlodipine across the skin is low. In vitro studies were performed with microneedle-treated porcine ear skin using vertical static Franz diffusion cells (PermeGear, Hellertown, PA, USA). The receiver chamber contained 5ml of PBS (pH7.4) and was constantly maintained at 37°C temperature with a water circulation jacket. The diffusion area of the skin was 1.77cm(2). The donor compartment was loaded with 1ml of the solution containing 2.5mg/ml of amlodipine besylate. The donor chamber was covered with parafilm to avoid evaporation. Passive diffusion across untreated porcine skin served as control. Aliquots were taken every 2h for 12h and analyzed by liquid chromatography-mass spectrometry. Transcutaneous flux of verapamil increased significantly from 8.75μg/cm(2)/h to 49.96μg/cm(2)/h across microneedle-roller treated porcine skin. Percutaneous flux of amlodipine besylate following the use of stainless steel microneedles was 22.39μg/cm(2)/h. Passive flux for the drug was 1.57μg/cm(2)/h. This enhancement of amlodipine flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05μg/cm(2)/h in comparison with passive diffusion flux of 0.19μg/cm(2)/h. The difference in flux values was also statistically significant. Stainless

  6. Rapidly Dissolving Microneedle Patches for Transdermal Iron Replenishment Therapy.

    Science.gov (United States)

    Maurya, Abhijeet; Nanjappa, Shivakumar H; Honnavar, Swati; Salwa, M; Murthy, S Narasimha

    2018-02-17

    The prevalence of iron deficiency anemia (IDA) is predominant in women and children especially in developing countries. The disorder affects cognitive functions and physical activity. Although oral iron supplementation and parenteral therapy remains the preferred choice of treatment, gastric side effects and risk of iron overload decreases adherence to therapy. Transdermal route is an established approach, which circumvents the side effects associated with conventional therapy. In this project, an attempt was made to investigate the use of rapidly dissolving microneedles loaded with ferric pyrophosphate (FPP) as a potential therapeutic approach for management of IDA. Microneedle array patches were made using the micromolding technique and tested in vitro using rat skin to check the duration required for dissolution/disappearance of needles. The ability of FPP-loaded microneedles to replenish iron was investigated in anemic rats. Rats were fed iron-deficient diet for 5 weeks to induce IDA following which microneedle treatment was initiated. Recovery of rats from anemic state was monitored by measuring hematological and biochemical parameters. Results from in vivo study displayed significant improvements in hemoglobin and serum iron levels after 2-week treatment with FPP-loaded microneedles. The study effectively demonstrated the potential of microneedle-mediated iron replenishment for treatment of IDA. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Treatment of acne vulgaris with fractional radiofrequency microneedling.

    Science.gov (United States)

    Kim, Sang Tae; Lee, Kang Hoon; Sim, Hyung Jun; Suh, Kee Suck; Jang, Min Soo

    2014-07-01

    Fractional radiofrequency microneedling is a novel radiofrequency technique that uses insulated microneedles to deliver energy to the deep dermis at the point of penetration without destruction of the epidermis. It has been used for the treatment of various dermatological conditions including wrinkles, atrophic scars and hypertrophic scars. There have been few studies evaluating the efficacy of fractional radiofrequency microneedling in the treatment of acne, and none measuring objective parameters like the number of inflammatory and non-inflammatory acne lesions or sebum excretion levels. The safety and efficacy of fractional radiofrequency microneedling in the treatment of acne vulgaris was investigated. In a prospective clinical trial, 25 patients with moderate to severe acne were treated with fractional radiofrequency microneedling. The procedure was carried out three times at 1-month intervals. Acne lesion count, subjective satisfaction score, sebum excretion level and adverse effects were assessed at baseline and at 4, 8 and 12 weeks after the first treatment as well as 4, 8 and 12 weeks after the last treatment. Number of acne lesions (inflammatory and non-inflammatory) decreased. Sebum excretion and subjective satisfaction were more favorable at every time point compared with the baseline values (P acne vulgaris. © 2014 Japanese Dermatological Association.

  8. A Three-Dimensional Enormous Surface Area Aluminum Microneedle Array with Nanoporous Structure

    OpenAIRE

    Chen, Po Chun; Hsieh, Sheng Jen; Chen, Chien Chon; Zou, Jun

    2013-01-01

    We proposed fabricating an aluminum microneedle array with a nanochannel structure on the surface by combining micromachining, electrolyte polishing, and anodization methods. The microneedle array provides a three-dimensional (3D) structure that possesses several hundred times more surface area than a traditional nanochannel template. Therefore, the microneedle array can potentially be used in many technology applications. This 3D microneedle array device can not only be used for painless inj...

  9. Successful application of large microneedle patches by human volunteers

    OpenAIRE

    Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F.

    2017-01-01

    We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600??m), were prepared from aqueous blends of 15% w/w Gantrez? S97 and 7.5% w/w poly(ethyleneglycol) 10,000?Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500??m. Ten human volunteers successfully self-inserted the microneedl...

  10. Transdermal Delivery of siRNA through Microneedle Array

    Science.gov (United States)

    Deng, Yan; Chen, Jiao; Zhao, Yi; Yan, Xiaohui; Zhang, Li; Choy, Kwongwai; Hu, Jun; Sant, Himanshu J.; Gale, Bruce K.; Tang, Tao

    2016-02-01

    Successful development of siRNA therapies has significant potential for the treatment of skin conditions (alopecia, allergic skin diseases, hyperpigmentation, psoriasis, skin cancer, pachyonychia congenital) caused by aberrant gene expression. Although hypodermic needles can be used to effectively deliver siRNA through the stratum corneum, the major challenge is that this approach is painful and the effects are restricted to the injection site. Microneedle arrays may represent a better way to deliver siRNAs across the stratum corneum. In this study, we evaluated for the first time the ability of the solid silicon microneedle array for punching holes to deliver cholesterol-modified housekeeping gene (Gapdh) siRNA to the mouse ear skin. Treating the ear with microneedles showed permeation of siRNA in the skin and could reduce Gapdh gene expression up to 66% in the skin without accumulation in the major organs. The results showed that microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively.

  11. Direct microneedle array fabrication off a photomask to deliver collagen through skin.

    Science.gov (United States)

    Kochhar, Jaspreet Singh; Anbalagan, Parthiban; Shelar, Sandeep Balu; Neo, Jun Kai; Iliescu, Ciprian; Kang, Lifeng

    2014-07-01

    To fabricate microneedle arrays directly off a photomask using a simple photolithographical approach and evaluate their potential for delivering collagen. A simple photolithographical approach was developed by using photomask consisting of embedded micro-lenses that govern microneedle geometry in a mould free process. Microneedle length was controlled by use of simple glass scaffolds as well as addition of backing layer. The fabricated arrays were tested for their mechanical properties by using a force gauge as well as insertion into human skin with trypan blue staining. Microneedle arrays were then evaluated for the delivery of fluorescent collagen, which was evaluated using a confocal laser scanning microscope. Microneedles with sharp tips ranging between 41.5 ± 8.4 μm and 71.6 ± 13.7 μm as well as of two different lengths of 1336 ± 193 μm and 957 ± 171 μm were fabricated by using the photomasks. The microneedles were robust and resisted fracture forces up to 25 N. They were also shown to penetrate cadaver human skin samples with ease; especially microneedle arrays with shorter length of 957 μm penetrated up to 72% of needles. The needles were shown to enhance permeation of collagen through cadaver rat skin, as compared to passive diffusion of collagen. A simple and mould free approach of fabricating polymeric microneedle array is proposed. The fabricated microneedle arrays enhance collagen permeation through skin.

  12. Iontophoretic and Microneedle Mediated Transdermal Delivery of Glycopyrrolate

    Directory of Open Access Journals (Sweden)

    Meera Gujjar

    2014-12-01

    Full Text Available Purpose: The objective of this study was to investigate the use of iontophoresis, soluble microneedles and their combination for the transdermal delivery of glycopyrrolate. Methods: In vitro permeation was tested using full thickness porcine ear skin mounted onto Franz diffusion cells. Iontophoresis (0.5 mA/cm2 was done for 4 h using Ag/AgCl electrodes. For microneedles, three line array (27 needles/line of maltose microneedles were used to microporate the skin prior to mounting. Pore uniformity was determined by taking fluorescent images of distribution of calcein into pores and processing the images using an image analysis tool, which measured the fluorescent intensity in and around each pore to provide a pore permeability index (PPI. The donor chamber contained 500 µL of a 1 mg/mL solution of glycopyrrolate, and the receptor chamber contained 5 mL of 50 mM NaCl in deionized water. Samples were collected at predetermined time points over a period of 24 h and analyzed by HPLC. Skin irritation testing was performed with a 3D cell culture kit of human skin. MTT assay determined cell viability; viability less than 50% was considered irritant. Results: A control experiment which investigated passive permeation of glycopyrrolate delivered an average cumulative amount of 24.92 ± 1.77 µg/cm2 at 24 h, while microneedle pretreatment increased permeability to 46.54 ± 6.9 µg/cm2. Both iontophoresis (158.53 ± 17.50 µg/cm2 and a combination of iontophoresis and microneedles (182.43 ± 20.06 µg/ cm2 significantly increased delivery compared to passive and microneedles alone. Glycopyrrolate solution was found to be nonirritant with cell viability of 70.4% ± 5.03%. Conclusion: Iontophoresis and a combination of iontophoresis with microneedle pretreatment can be effectively used to enhance the transdermal delivery of glycopyrrolate. Glycopyrrolate was found to be non-irritant to skin.

  13. Dissolving microneedle patches for dermal vaccination

    OpenAIRE

    Leone, M.; Monkare, J.T.; Bouwstra, J.A.; Kersten, G.F.A.

    2017-01-01

    The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (e.g. pain, needle-stick injuries or needle re-use). This review focuses on dissolving microneedles that after penetration into the skin dissolve releasing the encapsulated antige...

  14. Microneedle patches for vaccination in developing countries.

    Science.gov (United States)

    Arya, Jaya; Prausnitz, Mark R

    2016-10-28

    Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization rates have risen since the introduction of the Expanded Program on Immunization (EPI), there remain major challenges to more effective vaccination in developing countries. As a possible solution, microneedle patches containing an array of micron-sized needles on an adhesive backing have been developed to be used for vaccine delivery to the skin. These microneedle patches can be easily and painlessly applied by pressing against the skin and, in some designs, do not leave behind sharps waste. The patches are single-dose, do not require reconstitution, are easy to administer, have reduced size to simplify storage, transportation and waste disposal, and offer the possibility of improved vaccine immunogenicity, dose sparing and thermostability. This review summarizes vaccination challenges in developing countries and discusses advantages that microneedle patches offer for vaccination to address these challenges. We conclude that microneedle patches offer a powerful new technology that can enable more effective vaccination in developing countries. Copyright © 2015. Published by Elsevier B.V.

  15. Hydrogel-forming microneedle arrays exhibit antimicrobial properties: potential for enhanced patient safety.

    Science.gov (United States)

    Donnelly, Ryan F; Singh, Thakur Raghu Raj; Alkilani, Ahlam Zaid; McCrudden, Maelíosa T C; O'Neill, Shannon; O'Mahony, Conor; Armstrong, Keith; McLoone, Nabla; Kole, Prashant; Woolfson, A David

    2013-07-15

    We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture were greater than 10⁵ cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 10⁴ microorganisms penetrated into the viable tissue and 10⁶ cfu of Candida albicans and Staphylococcus epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation.

    Science.gov (United States)

    Lutton, Rebecca E M; Moore, Jessica; Larrañeta, Eneko; Ligett, Stephen; Woolfson, A David; Donnelly, Ryan F

    2015-08-01

    With interest in microneedles as a novel drug transdermal delivery system increasing rapidly since the late 1990s (Margetts and Sawyer Contin Educ Anaesthesia Crit Care Pain. 7(5):171-76, 2007), a diverse range of microneedle systems have been fabricated with varying designs and dimensions. However, there are still very few commercially available microneedle products. One major issue regarding microneedle manufacture on an industrial scale is the lack of specific quality standards for this novel dosage form in the context of Good Manufacturing Practice (GMP). A range of mechanical characterisation tests and microneedle insertion analysis techniques are used by researchers working on microneedle systems to assess the safety and performance profiles of their various designs. The lack of standardised tests and equipment used to demonstrate microneedle mechanical properties and insertion capability makes it difficult to directly compare the in use performance of candidate systems. This review highlights the mechanical tests and insertion analytical techniques used by various groups to characterise microneedles. This in turn exposes the urgent need for consistency across the range of microneedle systems in order to promote innovation and the successful commercialisation of microneedle products.

  17. Biocompatible polymer microneedle for topical/dermal delivery of tranexamic acid.

    Science.gov (United States)

    A Machekposhti, S; Soltani, M; Najafizadeh, P; Ebrahimi, S A; Chen, P

    2017-09-10

    Recently-introduced biocompatible polymeric microneedles offer an efficient method for drug delivery. Tranexamic acid is a novel drug for treating melasma that is administered both locally and orally and inhibits excessive melanin via melanocyte. The tranexamic acid biocompatible polymer microneedle used in this study was fabricated from PVP and methacrylic acid, using the lithography method. The required mechanical strength to pierce skin was attained by optimizing the ratio of PVP to methacrylic acid. Acute dermal toxicity was done, and drug diffusion in skin layers was simulated by calculating the diffusion coefficient of tranexamic acid in interstitial fluid (plasma). The biocompatible polymer microneedle was fabricated at 60°C. Needles could sustain 0.6N that is enough to pierce stratum corneum. 34% of the released drug was locally effective and the rest permeated through the skin. The pyramidal polymer microneedle in this study was fully released in skin in approx. 7h. This polymer microneedle has no dermal toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery.

    Science.gov (United States)

    Tu, Jing; Du, Guangsheng; Reza Nejadnik, M; Mönkäre, Juha; van der Maaden, Koen; Bomans, Paul H H; Sommerdijk, Nico A J M; Slütter, Bram; Jiskoot, Wim; Bouwstra, Joke A; Kros, Alexander

    2017-08-01

    To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA). Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied. The synthesized MSNs demonstrated efficient loading of OVA with a maximum loading capacity of about 34% and the lipid bilayer enhanced the colloidal stability of the MSNs. Uptake of OVA loaded in LB-MSN-OVA by BMDCs was higher than that of free OVA, suggesting effective targeting of LB-MSN-OVA to antigen-presenting cells. Microneedles were readily coated with LB-MSN-OVA at pH 5.8, yielding 1.5 μg of encapsulated OVA per microneedle array. Finally, as a result of the pyridine modification, LB-MSN-OVA were effectively released from the microneedles upon piercing the skin. Microneedle arrays coated with LB-MSN-OVA were successfully developed and shown to be suitable for intradermal delivery of the encapsulated protein antigen.

  19. Increasing topical anesthetic efficacy with microneedle application.

    Science.gov (United States)

    Buhsem, Ömer; Aksoy, Alper; Kececi, Yavuz; Sir, Emin; Güngör, Melike

    2016-10-01

    Since topical anesthetics alone seldom provide adequate analgesia for laser resurfacing procedures, injectable forms of anesthesia are often required. However, their application is uncomfortable for the patient. In this study, it is investigated whether microneedle application would enhance the efficacy of topical anesthetics. Forty-seven patients participated in the study. Topical anesthetic agent EMLA was applied to the whole face of the patients. Microneedle treatment was applied to one side of the face with a roller-type device. Whole-face carbon dioxide laser resurfacing therapy was carried out then. The pain that patients experienced was assessed by using visual analog scale (VAS) method. VAS scores of two sides of the face were compared by using Wilcoxon signed-rank test. The mean of VAS score of the microneedle treated side was 2.1 ± 1.1 while that of the untreated side was 5.9 ± 0.9 and this difference was statistically significant (Wilcoxon signed-rank test, the Z-value is - 5.9683 and the p-value is < 0.001). This study revealed that microneedle application, with a roller-type device, is a safe and easy procedure in providing sufficient anesthesia for facial laser resurfacing without the need for supplementary nerve blocks or injections.

  20. Microneedle-mediated delivery of viral vectored vaccines.

    Science.gov (United States)

    Zaric, Marija; Ibarzo Yus, Bárbara; Kalcheva, Petya Petrova; Klavinskis, Linda Sylvia

    2017-10-01

    Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors. Areas covered: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination. Expert opinion: Simple, economic and efficacious vaccine delivery methods are needed to improve health outcomes and manage possible outbreaks of new emerging viruses. Understanding what innate/inflammatory signals are required to induce both immediate and long-term responses remains a major hurdle in the development of the effective vaccines. One approach to meet these needs is microneedle-mediated viral vector vaccination. In order for this technology to fulfil this potential the industry must invest significantly to further develop its design, production, biosafety, delivery and large-scale manufacturing.

  1. Multilayered pyramidal dissolving microneedle patches with flexible pedestals for improving effective drug delivery.

    Science.gov (United States)

    Lau, Shinying; Fei, Jie; Liu, Haoran; Chen, Weixing; Liu, Ran

    2017-11-10

    Dissolving microneedles have been employed as a safe and convenient transdermal delivery system for drugs and vaccines. To improve effective drug delivery, a multilayered pyramidal dissolving microneedle patch, composed of silk fibroin tips with the ability of robust mechanical strength, rapid dissolution and drug release supported on a flexible polyvinyl alcohol (PVA) pedestal is reported. To show the utility of this approach the ability of the fabricated microneedles to deliver insulin is demonstrated. The dissolving microneedles have sufficient mechanical strength to be inserted into abdomen skin of mice to a depth of approximately 150μm, and release their encapsulated insulin into the skin to cause a hypoglycemic effect. The fabrication of microneedles avoids high temperature which benefits storage stability at room temperature for 20d. This result indicates >99.4% of insulin remained in the microneedles. In comparison to traditional needle-based administration, the proposed multilayered pyramidal dissolving microneedle patches enable self-administration, miniaturization, pain-free administration, drug delivery and drug stability, all being important features in needle free drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Enhancing DNA delivery into the skin with a motorized microneedle device.

    Science.gov (United States)

    Yan, Guang; Arelly, Naresh; Farhan, Nashid; Lobo, Shabbir; Li, Henan

    2014-02-14

    The purpose of this study was to evaluate a motorized microneedle device in delivery of DNA into skin for gene expression. A plasmid DNA encoding both luciferase (Luc) and enhanced green fluorescent protein (EGFP) was delivered into rat skin by puncturing the skin with the microneedle device. Puncturing rat skin with a pre-applied DNA solution on the skin showed much higher luciferase gene expression than that with the procedure of puncturing the skin first then applied the DNA solution. The microneedle puncturing method was more efficient than intradermal injection method in generating high gene expression in the skin. There was no significant difference in the skin gene expression when rat skin was punctured with the microneedle device of different microneedle lengths (0.25 mm, 0.5mm or 0.75 mm). On the other hand, there was a significant difference in the skin gene expression between the short (10s) and the long puncturing durations (30 or 60s), with longer puncturing duration showed higher gene expression. Puncturing the skin with longer needles (0.75 mm) caused some skin damage, while puncturing the skin with shorter microneedle length (0.25 mm) caused only minimal skin damage. The EGFP gene expression was observed predominately in the epidermis layer of the skin from the puncturing method in delivery of DNA into the skin. In summary, the motorized microneedle device could have great potential in skin gene delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. The use of biodegradable microneedle patches to increase penetration of topical steroid for prurigo nodularis.

    Science.gov (United States)

    Shin, Jung U; Kim, Jung Dong; Kim, Hong Kee; Kang, Hong Kyu; Joo, Chulmin; Lee, Ju Hee; Jeong, Do Hyeon; Song, Seungri; Chu, Howard; Lee, Jung Soo; Lee, Hemin; Lee, Kwang Hoon

    2018-02-01

    The stratum corneum is an almost impermeable barrier. Recently, microneedles have been used to increase drug delivery passing the stratum corneum by incorporating the drug within the microneedle or by coating the surface of the microneedle with the drug. This study was performed to investigate whether applying a biodegradable microneedle patch after topical steroid application increases penetration of the steroid in vitro, as well as treatment efficacy in patients with prurigo nodularis. In vitro penetration of topical steroids after biodegradable microneedle patch application was measured using a 3D skin model. To evaluate the treatment efficacy of the combination of biodegradable microneedle and topical steroids, a split-body clinical study was performed. Penetration of topical steroid in the in vitro skin model was significantly greater in the microneedle-applied skin. In a split-body clinical study with prurigo nodularis patients, the area and height of skin lesions decreased after four weeks of treatment on both sides, however, the microneedle patch side exhibited a significantly greater decrease in both area and height, compared to the control side. The pruritus visual analogue scale was also significantly lower on the microneedle side. We suggest that simply applying a microneedle patch after topical steroid application could be a useful strategy for treating refractory skin diseases such as prurigo nodularis.

  4. Development of a thermostable microneedle patch for influenza vaccination

    Science.gov (United States)

    Mistilis, Matthew; Bommarius, Andreas S; Prausnitz, Mark R.

    2017-01-01

    The goal of this study is to develop thermostable microneedle patch formulations for influenza vaccine that can be partially or completely removed from the cold chain. During vaccine drying associated with microneedle patch manufacturing, ammonium acetate and HEPES buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane led to increased stability compared to drying on stainless steel. A number of excipients, mostly polysaccharides and some amino acids, further stabilized the influenza vaccine during drying. Over longer time scales of storage, combinations of stabilizers preserved the most vaccine activity. Finally, dissolving microneedle patches formulated with arginine and calcium heptagluconate had no significant activity loss for all three strains of seasonal influenza vaccine during storage at room temperature for six months. We conclude that appropriately formulated microneedle patches can exhibit remarkable thermostability that could enable storage and distribution of influenza vaccine outside the cold chain. PMID:25448542

  5. Determination of parameters for successful spray coating of silicon microneedle arrays.

    Science.gov (United States)

    McGrath, Marie G; Vrdoljak, Anto; O'Mahony, Conor; Oliveira, Jorge C; Moore, Anne C; Crean, Abina M

    2011-08-30

    Coated microneedle patches have demonstrated potential for effective, minimally invasive, drug and vaccine delivery. To facilitate cost-effective, industrial-scale production of coated microneedle patches, a continuous coating method which utilises conventional pharmaceutical processes is an attractive prospect. Here, the potential of spray-coating silicon microneedle patches using a conventional film-coating process was evaluated and the key process parameters which impact on coating coalescence and weight were identified by employing a fractional factorial design to coat flat silicon patches. Processing parameters analysed included concentration of coating material, liquid input rate, duration of spraying, atomisation air pressure, gun-to-surface distance and air cap setting. Two film-coating materials were investigated; hydroxypropylmethylcellulose (HPMC) and carboxymethylcellulose (CMC). HPMC readily formed a film-coat on silicon when suitable spray coating parameter settings were determined. CMC films required the inclusion of a surfactant (1%, w/w Tween 80) to facilitate coalescence of the sprayed droplets on the silicon surface. Spray coating parameters identified by experimental design, successfully coated 280μm silicon microneedle arrays, producing an intact film-coat, which follows the contours of the microneedle array without occlusion of the microneedle shape. This study demonstrates a novel method of coating microneedle arrays with biocompatible polymers using a conventional film-coating process. It is the first study to indicate the thickness and roughness of coatings applied to microneedle arrays. The study also highlights the importance of identifying suitable processing parameters when film coating substrates of micron dimensions. The ability of a fractional factorial design to identify these critical parameters is also demonstrated. The polymer coatings applied in this study can potentially be drug loaded for intradermal drug and vaccine delivery

  6. Single-Step Fabrication of Computationally Designed Microneedles by Continuous Liquid Interface Production.

    Directory of Open Access Journals (Sweden)

    Ashley R Johnson

    Full Text Available Microneedles, arrays of micron-sized needles that painlessly puncture the skin, enable transdermal delivery of medications that are difficult to deliver using more traditional routes. Many important design parameters, such as microneedle size, shape, spacing, and composition, are known to influence efficacy, but are notoriously difficult to alter due to the complex nature of microfabrication techniques. Herein, we utilize a novel additive manufacturing ("3D printing" technique called Continuous Liquid Interface Production (CLIP to rapidly prototype sharp microneedles with tuneable geometries (size, shape, aspect ratio, spacing. This technology allows for mold-independent, one-step manufacturing of microneedle arrays of virtually any design in less than 10 minutes per patch. Square pyramidal CLIP microneedles composed of trimethylolpropane triacrylate, polyacrylic acid and photopolymerizable derivatives of polyethylene glycol and polycaprolactone were fabricated to demonstrate the range of materials that can be utilized within this platform for encapsulating and controlling the release of therapeutics. These CLIP microneedles effectively pierced murine skin ex vivo and released the fluorescent drug surrogate rhodamine.

  7. Current aspects of formulation efforts and pore lifetime related to microneedle treatment of skin.

    Science.gov (United States)

    Milewski, Mikolaj; Brogden, Nicole K; Stinchcomb, Audra L

    2010-05-01

    The efficacy of microneedles in the area of transdermal drug delivery is well documented. Multiple studies have shown that enhancement of skin permeation by means of the creation of microscopic pores in the stratum corneum can greatly improve the delivery rates of drugs. However, skin pretreatment with microneedles is not the only factor affecting drug transport rates. Other factors, including drug formulation and rate of micropore closure, are also important for optimizing delivery by this route. This review aims to highlight work that has been done in these areas, with an emphasis on drug formulation parameters that affect transdermal flux. This review creates an appreciation for the many factors affecting microneedle-enhanced delivery. Most results clearly indicate that microneedle skin pretreatment by itself may have different effects on drug transport depending on the formulation used, and formulation characteristics have different effects on the transport through untreated skin and microneedle-treated skin. Several formulation approaches are reported to optimize microneedle-enhanced drug delivery, including co-solvent use, vesicular, nanoparticulate and gel systems. In addition to well-established factors that affect microneedle-assisted delivery (geometry, type of microneedle, etc.), formulation and pore viability are also critical factors that must be considered.

  8. Development of a three-microneedle device for hypodermic drug delivery and clinical application.

    Science.gov (United States)

    Fukamizu, Hidekazu; Fujiwara, Masao; Kim, Taishi; Matsushita, Yuki; Tokura, Yoshiki

    2012-08-01

    There is a potential use for intradermic or hypodermic drug delivery in skin surgery or aesthetic surgery. Hypodermic delivery with the use of a noninvasive device can be a more useful, reliable, and effective administration route to obtain higher compliance. The authors developed a microneedle device composed of three fine needles (three-microneedle device). The tip of each needle was fabricated with a bevel angle to release a drug broadly into the tissue in a horizontal fashion. In this study, the authors investigated the usefulness of this newly developed three-microneedle device for hypodermic liquid injection, focusing on the optimum insertion depth and the diffusion of injected materials to the tissue. The authors also assessed the efficacy of and patient satisfaction with three-microneedle device injections of botulinum toxin type A for wrinkle reduction in patients with glabellar rhytides. The three-microneedle device yielded consistent results in hypodermal diffusion. On India ink diffusion test and ultrasonographic imaging, three-microneedle device injection showed a broad diffusion in horizontal extension, as compared with usual 31-gauge needle injection. The efficiency and satisfaction of the patients receiving botulinum toxin type A with the three-microneedle device were highly rated. Three-microneedle device delivery enables accurate and broad diffusion of injected substances, thus reducing the total dose and/or injection number of drugs. Therapeutic, IV.

  9. Long-term stability of influenza vaccine in a dissolving microneedle patch.

    Science.gov (United States)

    Mistilis, Matthew J; Joyce, Jessica C; Esser, E Stein; Skountzou, Ioanna; Compans, Richard W; Bommarius, Andreas S; Prausnitz, Mark R

    2017-04-01

    This study tested the hypothesis that optimized microneedle patch formulations can stabilize trivalent subunit influenza vaccine during long-term storage outside the cold chain and when exposed to potential stresses found during manufacturing and storage. Formulations containing combinations of trehalose/sucrose, sucrose/arginine, and arginine/heptagluconate were successful at retaining most or all vaccine activity during storage at 25 °C for up to 24 months as determined by ELISA assay. The best formulation of microneedle patches contained arginine/heptagluconate, which showed no significant loss of vaccine activity during the study. To validate these in vitro findings, mice were immunized using trivalent influenza vaccine stored in microneedle patches for more than 1 year at 25 °C, which elicited antibody titers greater than or equal to fresh liquid vaccine delivered by intradermal injection, indicating the retention of immunogenicity during storage. Finally, influenza vaccine in microneedle patches lost no significant activity during exposure to 60 °C for 4 months, multiple freeze-thaw cycles, or electron beam irradiation. We conclude that optimally formulated microneedle patches can retain influenza vaccine activity during extended storage outside the cold chain and during other environmental stresses, which suggests the possibility of microneedle patch storage on pharmacy shelves without refrigeration.

  10. Efficacy of a bleomycin microneedle patch for the treatment of warts.

    Science.gov (United States)

    Ryu, Ha Ryeong; Jeong, Hye-Rin; Seon-Woo, Hye-Seung; Kim, Jung Soo; Lee, Seul Ki; Kim, Hee Joo; Baek, Jin Ok; Park, Jung-Hwan; Roh, Joo Young

    2018-02-01

    Warts are a common skin disease caused by infection of the human papilloma virus. Most treatments involving physical destruction of the infected cells, such as cryotherapy and electrocautery, are limited by intense pain, failure, or recurrences. Our aim was to compare the therapeutic effects of a newly developed bleomycin microneedle patch with cryotherapy in the treatment of warts. Forty-two patients with more than two wart lesions were included in the study. The two treatment modalities were randomly applied to different warts on each patient. Treatment efficacy was assessed using the Physician's Global Assessment (PGA) and the Patient's Global Assessment (PaGA). Mean PGA and PaGA scores were not significantly different between cryotherapy and bleomycin microneedle patch treatment. It was also determined that the mean size of all the warts treated with either modality shrank about equally at weeks 8 and 16 after initial treatment. Thus, treatment efficacy of the bleomycin microneedle patch was comparable to that of conventional cryotherapy. According to a visual analogue scale of pain, bleomycin microneedle patch treatment was significantly less painful than cryotherapy (p microneedle patch was more tolerable for patients who were reluctant to receive the painful treatment. Thus, the bleomycin microneedle patch can be an effective, convenient, and innovative treatment modality for warts.

  11. Microneedle patches: usability and acceptability for self-vaccination against influenza.

    Science.gov (United States)

    Norman, James J; Arya, Jaya M; McClain, Maxine A; Frew, Paula M; Meltzer, Martin I; Prausnitz, Mark R

    2014-04-01

    While therapeutic drugs are routinely self-administered by patients, there is little precedent for self-vaccination. Convenient self-vaccination may expand vaccination coverage and reduce administration costs. Microneedle patches are in development for many vaccines, but no reports exist on usability or acceptability. We hypothesized that naïve patients could apply patches and that self-administered patches would improve stated intent to receive an influenza vaccine. We conducted a randomized, repeated measures study with 91 venue-recruited adults. To simulate vaccination, subjects received placebo microneedle patches given three times by self-administration and once by the investigator, as well as an intramuscular injection of saline. Seventy participants inserted patches with thumb pressure alone and the remainder used snap-based devices that closed shut at a certain force. Usability was assessed by skin staining and acceptability was measured with an adaptive-choice analysis. The best usability was seen with the snap device, with users inserting a median value of 93-96% of microneedles over three repetitions. When a self-administered microneedle patch was offered, intent to vaccinate increased from 44% to 65% (CI: 55-74%). The majority of those intending vaccination would prefer to self-vaccinate: 64% (CI: 51-75%). There were no serious adverse events associated with use of microneedle patches. The findings from this initial study indicate that microneedle patches for self-vaccination against influenza are usable and may lead to improved vaccination coverage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Mesotherapy, Microneedling, and Chemical Peels.

    Science.gov (United States)

    Lee, Johnson C; Daniels, Mark A; Roth, Malcolm Z

    2016-07-01

    Mesotherapy, microneedling, and chemical peels are minimally invasive techniques used to combat facial aging. Chemical peeling is one of the oldest methods of facial rejuvenation. By using different chemicals in various combinations, strengths, and application techniques, plastic surgeons can tailor a patient's treatment for optimal, safe, and consistent results. Mesotherapy and microneedling have emerged in the plastic surgery literature with increasingly complex indications. Both techniques have increased in popularity although research into efficacy and long-term results is lagging. With a thorough understanding of patients and the modalities available, plastic surgeons can use the appropriate minimally invasive technique to provide patients with desired skin changes. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A novel method of microneedle array fabrication using inclined deep x-ray exposure

    International Nuclear Information System (INIS)

    Moon, Sang Jun; Jin, Chun Yan; Lee, Seung S

    2006-01-01

    We report a novel fabrication method for the microneedle array with a 3-dimensional feature and its replication method; 'Hot-pressing' process with bio-compatible material, PLLA (Poly L-LActide). Using inclined deep X-ray exposure technique, we fabricate a band type microneedle array with a single body on the same material basement. Since the single body feature does not make adhesion problem with the microneedle shank and basement during peel-off step of a mold, the PMMA (Poly-Methyl-MethAcrylate) microneedle array mold insert can be used for mold process which is used with the soft material mold, PDMS (Poly-Di- Methyl-Siloxane). The side inclined deep X-ray exposure also makes complex 3-dimensional features by the regions which are not exposed during twice successive exposure steps. In addition, the successive exposure does not need an additional mask alignment after the first side exposure. The fabricated band type microneedle array mold inserts are assembled for large area patch type out-of-plane microneedle array. The bio-compatible microneedle array can be fabricated to the laboratory scale mass production by the single body PMMA mold insert and 'Hot-pressing' process

  14. A novel method of microneedle array fabrication using inclined deep x-ray exposure

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Sang Jun; Jin, Chun Yan; Lee, Seung S [Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), 373-1, Guseong-dong, Yuseong-dong, Daejeon (Korea, Republic of)

    2006-04-01

    We report a novel fabrication method for the microneedle array with a 3-dimensional feature and its replication method; 'Hot-pressing' process with bio-compatible material, PLLA (Poly L-LActide). Using inclined deep X-ray exposure technique, we fabricate a band type microneedle array with a single body on the same material basement. Since the single body feature does not make adhesion problem with the microneedle shank and basement during peel-off step of a mold, the PMMA (Poly-Methyl-MethAcrylate) microneedle array mold insert can be used for mold process which is used with the soft material mold, PDMS (Poly-Di- Methyl-Siloxane). The side inclined deep X-ray exposure also makes complex 3-dimensional features by the regions which are not exposed during twice successive exposure steps. In addition, the successive exposure does not need an additional mask alignment after the first side exposure. The fabricated band type microneedle array mold inserts are assembled for large area patch type out-of-plane microneedle array. The bio-compatible microneedle array can be fabricated to the laboratory scale mass production by the single body PMMA mold insert and 'Hot-pressing' process.

  15. Rapid fabrication method of a microneedle mold with controllable needle height and width.

    Science.gov (United States)

    Lin, Yen-Heng; Lee, I-Chi; Hsu, Wei-Chieh; Hsu, Ching-Hong; Chang, Kai-Ping; Gao, Shao-Syuan

    2016-10-01

    The main issue of transdermal drug delivery is that macromolecular drugs cannot diffuse through the stratum corneum of skin. Many studies have pursued micro-sized needles encapsulated with drugs to overcome this problem, as these needles can pierce the stratum corneum and allow drugs to enter the circulatory system of the human body. However, most microneedle fabrication processes are time-consuming and require expensive equipment. In this study, we demonstrate a rapid method for fabricating a microneedle mold using drawing lithography and a UV-cured resin. The mold was filled with a water-soluble material, polyvinylpyrrolidone (PVP), which was then demolded to produce a water-soluble microneedle array. The results of an in vitro skin insertion test using PVP microneedles and pig ear skin demonstrated the feasibility of the microneedle mold. In addition, by controlling the viscosity of the UV-cured resin through various heat treatments, microneedles with different heights and aspect ratios were produced. Compared with other methods, this technology significantly simplifies and accelerates the mold fabrication process. In addition, the required equipment is relatively simple and inexpensive. Through this technology, we can rapidly fabricate microneedle molds with controllable dimensions for various applications.

  16. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    Science.gov (United States)

    Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

  17. Dissolvable microneedle fabrication using piezoelectric dispensing technology.

    Science.gov (United States)

    Allen, Evin A; O'Mahony, Conor; Cronin, Michael; O'Mahony, Thomas; Moore, Anne C; Crean, Abina M

    2016-03-16

    Dissolvable microneedle (DMN) patches are novel dosage forms for the percutaneous delivery of vaccines. DMN are routinely fabricated by dispensing liquid formulations into microneedle-shaped moulds. The liquid formulation within the mould is then dried to create dissolvable vaccine-loaded microneedles. The precision of the dispensing process is critical to the control of formulation volume loaded into each dissolvable microneedle structure. The dispensing process employed must maintain vaccine integrity. Wetting of mould surfaces by the dispensed formulation is also an important consideration for the fabrication of sharp-tipped DMN. Sharp-tipped DMN are essential for ease of percutaneous administration. In this paper, we demonstrate the ability of a piezoelectric dispensing system to dispense picolitre formulation volumes into PDMS moulds enabling the fabrication of bilayer DMN. The influence of formulation components (trehalose and polyvinyl alcohol (PVA) content) and piezoelectric actuation parameters (voltage, frequency and back pressure) on drop formation is described. The biological integrity of a seasonal influenza vaccine following dispensing was investigated and maintained voltage settings of 30 V but undermined at higher settings, 50 and 80 V. The results demonstrate the capability of piezoelectric dispensing technology to precisely fabricate bilayer DMN. They also highlight the importance of identifying formulation and actuation parameters to ensure controlled droplet formulation and vaccine stabilisation. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Microneedle, microneedle array and production method therefor

    OpenAIRE

    Berenschot, Johan W.; Wissink, Jeroen Mathijn; Tas, Niels Roelof; de Boer, Meint J.

    2009-01-01

    The present invention provides a microneedle, comprising a shaft of a monocrystalline material having at least three walls which are formed by a crystal plane of the monocrystalline material; and a tip connected to an end of the shaft comprising at least three walls which are formed by a crystal plane of the material. The material is preferably silicon. Two of the walls of the tip are formed by the same crystal planes as two walls of the shaft. These two walls are formed by a crystal plane. ...

  19. [Effect of microneedle combined with Lauromacrogol on skin capillary network: experimental study].

    Science.gov (United States)

    Xu, Sida; Wei, Qiang; Fan, Youfen; Chen, Shihai; Liu, Qingfeng; Yin, Guoqiang; Liao, Mingde; Sun, Yu

    2014-11-01

    To explore the effect of microneedle combined with Lauromacrogol on skin capillary network. 24 male Leghone (1.5-2.0 kg in weight) were randomly divided into three groups as group A (microneedle combined with Lauromacrogol), B (microneedle combined with physiological saline) , and C(control). The cockscombs were treated. The specimens were taken on the 7th, 14th, 21th , and 28th day postoperatively. HE staining, immunohistochemical staining and special staining were performed for study of the number of capillary and collagen I/III , as well as elastic fibers. The color of cockscombs in group A became lightening after treatment. The number of capillary decreased as showing by HE staining. The collagen I and III in group B was significantly different from that in group A and C (P microneedle combined with Lauromacrogol could effectively reduce the capillary in cockscomb without any tissue fibrosis. Microneedle can stimulate the proliferation of elastic fiber, so as to improve the skin ageing process.

  20. Blood-mimicking delivery in polygonal structure of inner quadrupletip microneedle with valveless micro-pump

    Science.gov (United States)

    Ibrahim, M. D.; Yunos, Y. S.; Rigit, A. R. H.; Mohtadzar, N. A. A.; Watanabe, N.; Sunami, Y.; Rahman, M. R. A.; Wong, L. K.; Mohtar, M. Z.

    2017-04-01

    This paper presents a titanium quadrupletip micro-needle integrated with a micro-pump with different inner designs, length and diameter of the micro-channels to measure and maximize the velocity flow in the micro-needle as blood delivered into human body. Titanium is used as the material of the micro-needle which are also the common material in manufacturing of micro-needle. The advancement of micro-needle technologies is improved in penetrating human outermost skin, stratum corneum and further to human blood vessels. The micro-needles with channel inner design of circular, square, hexagon, and dodecagon with quadruple tip designs are drawn with inner diameter parameter of 150μm and 100μm with two different channel length which are 10mm and 25mm. The characteristics of blood delivery in geometrically changed inner designs affect the output velocity in microneedle when the micropump is operating. The results showed that, when it is pumped at 0.04m/s, the blood velocity improved by 5.6% than when the pump is increased by 30% of its capacity. This is due to the backflow generated in the micropump.

  1. Fractional Microneedling: A Novel Method for Enhancement of Topical Anesthesia Before Skin Aesthetic Procedures.

    Science.gov (United States)

    El-Fakahany, Hasan; Medhat, Walid; Abdallah, Fahd; Abdel-Raouf, Hamza; Abdelhakeem, Mohammed

    2016-01-01

    Skin microneedling or fractional microneedle therapy is a recent approach used for skin rejuvenation or to enhance transdermal delivery of topical medications. The authors evaluated the efficacy of skin microneedling, using an automated device, to enhance the numbing effect of topical anesthesia, used before minimally invasive aesthetic approaches. Fifteen patients, looking for treatment of atrophic acne scars, were subjected to randomized split-face study comparing automated fractional skin microneedling (0.5 mm depth) followed by application of topical anesthetic cream (Lidocaine 2.5% + Prilocaine 2.5%) on one side of face, with topical anesthesia alone on the other side, followed by full face fractional microneedling treatment for postacne scars (2.5 mm depth). The treated sides (fractional needling + topical anesthesia) had significantly lower pain scores when compared with the nontreated sides (topical anesthesia alone). The scores of pain sensation, during the whole procedure, were statistically significantly (p aesthetic procedures can be enhanced with fractional microneedling pretreatment.

  2. Finite-element modelling and preliminary validation of microneedle-based electrodes for enhanced tissue electroporation.

    Science.gov (United States)

    Houlihan, Ruth; Grygoryev, Konstantin; Zhenfei Ning; Williams, John; Moore, Tom; O'Mahony, Conor

    2017-07-01

    This paper investigates the use of microneedle-based electrodes for enhanced testis electroporation, with specific application to the production of transgenic mice. During the design phase, finite-element software has been used to construct a tissue model and to compare the relative performance of electrodes employing a) conventional flat plates, b) microneedle arrays, and c) invasive needles. Results indicate that microneedle-based electrodes can achieve internal tissue field strengths which are an order of magnitude higher than those generated using conventional flat electrodes, and which are comparable to fields produced using invasive needles. Using a double-sided etching process, conductive microneedle arrays were then fabricated and used in prototype electrodes. In a series of mouse model experiments involving injection of a DNA vector expressing Green Fluorescent Protein (GFP), the performance of flat and microneedle electrodes was compared by measuring GFP expression after electroporation. The main finding, supported by experimental and simulated data, is that use of microneedle-based electrodes significantly enhanced electroporation of testis.

  3. Anti-arthritic effects of microneedling with bee venom gel

    Directory of Open Access Journals (Sweden)

    Mengdi Zhao

    2016-10-01

    Conclusions: Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction. Choose the 750 μm microneedle with 10N force on skin about 3 minutes, bee venom can play the optimal role, and the anti-inflammatory effect is obvious. Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.

  4. Stabilization of influenza vaccine enhances protection by microneedle delivery in the mouse skin.

    Directory of Open Access Journals (Sweden)

    Fu-Shi Quan

    2009-09-01

    Full Text Available Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.

  5. Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro.

    Science.gov (United States)

    Donnelly, Ryan F; Singh, Thakur Raghu Raj; Tunney, Michael M; Morrow, Desmond I J; McCarron, Paul A; O'Mahony, Conor; Woolfson, A David

    2009-11-01

    In this study we determined, for the first time, the ability of microorganisms to traverse microneedle-induced holes using two different in vitro models. When employing Silescol membranes, the numbers of Candida albicans, Pseudomonas aeruginosa and Staphylococcus epidermidis crossing the membranes were an order of magnitude lower when the membranes were punctured by microneedles rather than a 21G hypodermic needle. Apart from the movement of C. albicans across hypodermic needle-punctured membranes, where 40.2% of the microbial load on control membranes permeated the barrier over 24 h, the numbers of permeating microorganisms was less than 5% of the original microbial load on control membranes. Experiments employing excised porcine skin and radiolabelled microorganisms showed that the numbers of microorganisms penetrating skin beyond the stratum corneum were approximately an order of magnitude greater than the numbers crossing Silescol membranes in the corresponding experiments. Approximately 10(3) cfu of each microorganism adhered to hypodermic needles during insertion. The numbers of microorganisms adhering to MN arrays were an order of magnitude higher in each case. We have shown here that microneedle puncture resulted in significantly less microbial penetration than did hypodermic needle puncture and that no microorganisms crossed the viable epidermis in microneedle-punctured skin, in contrast to needle-punctured skin. Given the antimicrobial properties of skin, it is, therefore, likely that application of microneedle arrays to skin in an appropriate manner would not cause either local or systemic infection in normal circumstances in immune-competent patients. In supporting widespread clinical use of microneedle-based delivery systems, appropriate animal studies are now needed to conclusively demonstrate this in vivo. Safety in patients will be enhanced by aseptic or sterile manufacture and by fabricating microneedles from self-disabling materials (e

  6. Drug delivery into microneedle-porated nails from nanoparticle reservoirs.

    Science.gov (United States)

    Chiu, Wing Sin; Belsey, Natalie A; Garrett, Natalie L; Moger, Julian; Price, Gareth J; Delgado-Charro, M Begoña; Guy, Richard H

    2015-12-28

    This study demonstrates the potential of polymeric nanoparticles as drug reservoirs for sustained topical drug delivery into microneedle-treated human nail. Laser scanning confocal microscopy was used to image the delivery of a fluorescent model compound from nanoparticles into the nail. A label-free imaging technique, stimulated Raman scattering microscopy, was applied, in conjunction with two-photon fluorescence imaging, to probe the disposition of nanoparticles and an associated lipophilic 'active' in a microneedle-porated nail. The results provide clear evidence that the nanoparticles function as immobile reservoirs, sequestered on the nail surface and in the microneedle-generated pores, from which the active payload can be released and diffuse laterally into the nail over an extended period of time. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Insulin delivery systems combined with microneedle technology.

    Science.gov (United States)

    Jin, Xuan; Zhu, Dan Dan; Chen, Bo Zhi; Ashfaq, Mohammad; Guo, Xin Dong

    2018-03-29

    Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs ("poke and patch"), hollow MNs ("poke and flow") and reservoir-based swelling MNs ("poke and swell R-type"), and drug loaded MNs include coated MNs ("coat and poke"), dissolving MNs ("poke and release") and insulin incorporated swelling MNs ("poke and swell I-type"). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. "Poke and patch" approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. "Poke and flow" approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. "Poke and release" approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. "Poke and swell R-type" can be seen as a combination of "poke and flow" and "poke and patch" approach, while "poke and swell I-type" is an approach between "coat and

  8. Split face comparative study of microneedling with PRP versus microneedling with vitamin C in treating atrophic post acne scars

    Directory of Open Access Journals (Sweden)

    Simran Chawla

    2014-01-01

    Full Text Available Introduction: Acne scars are largely preventable complications of acne. 95% of the scars occur over the face thus impacting the quality of life. Correction of scars is the priority for acne patients. Materials and Methods: Thirty patients with post acne atrophic facial scars attending the OPD during the period from April to October 2013 were offered four sittings of microneedling with PRP on one side and microneedling with vitamin C on other side of the face at an interval of 1 month. Results: Twenty-seven out of the total 30 patients completed the treatment schedule. Two patients were lost to follow up and one dropped out of the study due to severe PIH. Mean age of the patients was 27.5 years. Out of 30 patients, 23 achieved reduction in scarring by one or two grades. Excellent response was seen in five (18.5% patients with platelet-rich plasma (PRP as compared to two (7% patients who received treatment with vitamin C according to physician′s assessment. As far as up gradation by 1 score is considered, i.e., good response, it was similar in both cases. Vitamin C did not prove to be as efficacious as PRP since 10 (37% patients had poor response in vitamin C-treated area compared to only 6 (22.2% patients who underwent PRP therapy, but vitamin C proved to be efficacious in dealing with post inflammatory hyper-pigmentation secondary to acne. Patients were more satisfied with PRP as compared to vitamin C. The results were evaluated and statistical analysis was done using SPSS 16.0.2. Conclusions: Overall results were better with microneedling and PRP. Vitamin C combined with microneedling also showed improvement with respect to firmness and smoothness of skin; as well as post inflammatory hyper-pigmentation. Microneedling combined with PRP proved to be good in treating boxcar and rolling scars but had limited efficacy in dealing with ice pick scars.

  9. [Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

    Science.gov (United States)

    Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

    2014-12-01

    In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.

  10. In vivo studies of transdermal nanoparticle delivery with microneedles using photoacoustic microscopy

    Science.gov (United States)

    Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

    2017-01-01

    Microneedle technology allows micron-sized conduits to be formed within the outermost skin layers for both localized and systemic delivery of therapeutics including nanoparticles. Histological methods are often employed for characterization, and unfortunately do not allow for the in vivo visualization of the delivery process. This study presents the utilization of optical resolution-photoacoustic microscopy to characterize the transdermal delivery of nanoparticles using microneedles. Specifically, we observe the in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and study the penetration, diffusion, and spatial distribution of the nanoparticles in the tissue. The promising results reveal that photoacoustic microscopy can be used as a potential imaging modality for the in vivo characterization of microneedles based drug delivery. PMID:29296482

  11. Coated microneedle arrays for transcutaneous delivery of live virus vaccines.

    Science.gov (United States)

    Vrdoljak, Anto; McGrath, Marie G; Carey, John B; Draper, Simon J; Hill, Adrian V S; O'Mahony, Conor; Crean, Abina M; Moore, Anne C

    2012-04-10

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. MICRONEEDLES AS A WAY TO INCREASE THE TRANSDERMAL INSULIN DELIVERY

    Directory of Open Access Journals (Sweden)

    E. G. Kuznetsova

    2016-01-01

    Full Text Available Aim: to prove the possibility of increasing the diffusion of insulin through the skin in vitro with pre-applying microneedles.Materials and methods. Microemulsion for transdermal therapeutic system of insulin has been used in vitro studies. Genetically engineered human insulin has been used in this research. Applicators with silicon microneedles (40 and 150 microns long have been used to enhance the diffusion fl ux of drug substance. The dynamics of insulin release from the transdermal therapeutic systems through the rabbit skin has been studied in glass Franz diffusion cells in analyzer diffusion of drugs HDT 1000 (Copley Scientifi c Ltd., UK. Insulin has been labeled with fl uorescein isothiocyanate to separate the insulin absorption spectrum from the spectra of native skin proteins at spectrophotometer measurements.Results. The amounts of insulin delivered through the skin in vitro after previous application of microneedles of 40 and 150 microns are 282.5 ± 61.1 and 372.3 ± 7.0 microgram, respectively. This is 1.4 and 1.9 times more than in the transdermal system without microneedles.Conclusion. The conditions for increasing the diffusion of insulin through the skin in a model transdermal therapeutic system with microneedles (length – 150 microns, duration of pre-application – 1 hour have been found.

  13. Coated microneedle arrays for transcutaneous delivery of live virus vaccines

    Science.gov (United States)

    Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

    2016-01-01

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8+ T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. PMID:22245683

  14. Transdermal influenza immunization with vaccine-coated microneedle arrays.

    Directory of Open Access Journals (Sweden)

    Dimitrios G Koutsonanos

    Full Text Available Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.Inactivated A/Aichi/2/68 (H3N2 influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM reference immunization.The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

  15. Microneedle physical contact as a therapeutic for abnormal scars

    OpenAIRE

    Yeo, David C.; Balmayor, Elizabeth R.; Schantz, Jan-Thorsten; Xu, Chenjie

    2017-01-01

    Background Abnormal (keloid and hypertrophic) scars are a significant affliction with no satisfactory single modality therapy to-date. Available options are often ineffective, painful, potentially hazardous, and require healthcare personnel involvement. Herein a self-administered microneedle device based on drug-free physical contact for inhibiting abnormal scars is reported. Its therapeutic activity through microneedle contact eliminates hazards associated with toxic anti-scarring drugs whil...

  16. Microneedle Enhanced Delivery of Cosmeceutically Relevant Peptides in Human Skin

    Science.gov (United States)

    Mohammed, Yousuf H.; Yamada, Miko; Lin, Lynlee L.; Grice, Jeffrey E.; Roberts, Michael S.; Raphael, Anthony P.; Benson, Heather A. E.; Prow, Tarl W.

    2014-01-01

    Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides. PMID:25033398

  17. Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin.

    Directory of Open Access Journals (Sweden)

    Yousuf H Mohammed

    Full Text Available Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides.

  18. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    Directory of Open Access Journals (Sweden)

    Hong X

    2013-09-01

    Full Text Available Xiaoyun Hong,1,2,* Liangming Wei,3,* Fei Wu,2,* Zaozhan Wu,2 Lizhu Chen,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, Shanghai, People's Republic of China; 2School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China; 3Research Institute of Micro/Nano Science and Technology, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. Keywords: microneedle, dissolving, biodegradable, sustained release

  19. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity

    Science.gov (United States)

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-07-01

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

  20. Polymer-based candle-shaped microneedle electrodes for electroencephalography on hairy skin

    Science.gov (United States)

    Arai, Miyako; Kudo, Yuta; Miki, Norihisa

    2016-06-01

    In this paper, we report on the optimization of the shape of dry microneedle electrodes for electroencephalography (EEG) on hairy locations and compare the electrodes we developed with conventional wet electrodes. We propose the use of SU-8-based candle-shaped microneedle electrodes (CMEs), which have pillars of 1.0 mm height and 0.4 mm diameter with a gap of 0.43 mm between pillars. Microneedles are formed on the top of the pillars. The shape was determined by how well the pillars can avoid hairs and support the microneedles to penetrate through the stratum corneum. The skin-electrode contact impedances of the fabricated CMEs were found to be higher and less stable than those of conventional wet electrodes. However, the CMEs successfully acquired signals with qualities as good as those of conventional wet electrodes. Given the usability of the CMEs, which do not require skin preparation or gel, they are promising alternatives to conventional wet electrodes.

  1. Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

    Directory of Open Access Journals (Sweden)

    Rhonda C Kines

    Full Text Available Human papilloma virus-like particles (HPV VLP serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV in HPV pseudovirions (PsV is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1 whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2 whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.

  2. Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future.

    Science.gov (United States)

    Levin, Yotam; Kochba, Efrat; Hung, Ivan; Kenney, Richard

    2015-01-01

    Intradermal immunization has become a forefront of vaccine improvement, both scientifically and commercially. Newer technologies are being developed to address the need to reduce the dose required for vaccination and to improve the reliability and ease of injection, which have been major hurdles in expanding the number of approved vaccines using this route of administration. In this review, 7 y of clinical experience with a novel intradermal delivery device, the MicronJet600, which is a registered hollow microneedle that simplifies the delivery of liquid vaccines, are summarized. This device has demonstrated both significant dose-sparing and superior immunogenicity in various vaccine categories, as well as in diverse subject populations and age groups. These studies have shown that intradermal delivery using this device is safe, effective, and preferred by the subjects. Comparison with other intradermal devices and potential new applications for intradermal delivery that could be pursued in the future are also discussed.

  3. Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery.

    Science.gov (United States)

    Hwa, Kuo-Yuan; Chang, Vincent H S; Cheng, Yao-Yi; Wang, Yue-Da; Jan, Pey-Shynan; Subramani, Boopathi; Wu, Min-Ju; Wang, Bo-Kai

    2017-09-19

    Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

  4. Fabrication and Analysis of Tapered Tip Silicon Microneedles for MEMS based Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Muhammad Waseem Ashraf

    2010-11-01

    Full Text Available In this paper, a novel design of transdermal drug delivery (TDD system is presented. The proposed system consists of controlled electronic circuit and microelectromechanical system (MEMS based devices like microneedles, micropump, flow sensor, and blood pressure sensor. The aim of this project is to develop a system that can eliminate the limitations associated with oral therapy. In this phase tapered tip silicon microneedles have been fabricated using inductively coupled plasma (ICP etching technology. Using ANSYS, simulation of microneedles has been conducted before the fabrication process to test the design suitability for TDD. More over multifield analysis of reservoir integrated with microneedle array using piezoelectric actuator has also been performed. The effects of frequency and voltage on actuator and fluid flow rate through 6×6 microneedle array have been investigated. This work provides envisage data to design suitable devices for TDD.

  5. Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans

    Science.gov (United States)

    Brogden, Nicole K.; Banks, Stan L.; Crofford, Leslie J.; Stinchcomb, Audra L.

    2013-01-01

    Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. Purpose the purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans. Methods Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application. Results Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n = 6), vs. 72 hours in Group 2 (placebo + naltrexone, n = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores). Conclusion This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases. PMID:23761054

  6. Hyaluronic acid microneedle patch for the improvement of crow's feet wrinkles.

    Science.gov (United States)

    Choi, Sun Young; Kwon, Hyun Jung; Ahn, Ga Ram; Ko, Eun Jung; Yoo, Kwang Ho; Kim, Beom Joon; Lee, Changjin; Kim, Daegun

    2017-11-01

    Hyaluronic acid (HA) has an immediate volumizing effect, due to its strong water-binding potential, and stimulates fibroblasts, causing collagen synthesis, with short- and long-term effects on wrinkle improvement. We investigated the efficacy and safety of HA microneedle patches for crow's feet wrinkles. Using a randomized spilt-face design, we compared microneedle patches with a topical application containing the same active ingredients. We enrolled 34 Korean female subjects with mild to moderate crow's feet wrinkles. The wrinkle on each side of the subject's face was randomly assigned to a HA microneedle patch or HA essence application twice a week for 8 weeks. Efficacy was evaluated at weeks 2, 4, and 8. Skin wrinkles were measured as average roughness using replica and PRIMOS. Skin elasticity was assessed using a cutometer. Two independent blinded dermatologists evaluated the changes after treatment using the global visual wrinkle assessment score. Subjects assessed wrinkles using the subject global assessment score. Skin wrinkles were significantly reduced and skin elasticity significantly increased in both groups, although improvement was greater in the patch group at week 8 after treatment. In the primary and cumulative skin irritation tests, the HA microneedle patch did not induce any skin irritation. The HA microneedle patch is more effective than the HA essence for wrinkle improvement and is a safe and convenient without skin irritation. © 2017 Wiley Periodicals, Inc.

  7. Microneedles from Fishscale-Nanocellulose Blends Using Low Temperature Mechanical Press Method.

    Science.gov (United States)

    Olatunji, Ololade; Olsson, Richard T

    2015-09-24

    Fish scale biopolymer blended with nanocellulose crystals is used for production of microneedles applying mechanical press microfabrication and the effect of nanocellulose on microfabrication, water absorption, moisture stability and mechanical properties of the microneedles is reported. The results show that microneedles produced from the nanocellulose loaded fish scale biopolymer requires higher temperature for micromolding (80 ± 5 °C) than microneedles from only fish scale biopolymer, which were moldable at 50 ± 5 °C. The mechanical properties of the fish scale biopolymer-nanocellulose (FSBP-NC) films showed that the addition of nanocellulose (NC) resulted in lower elongation and higher tensile stress compared to fish scale biopolymer (FSBP) films. The nanocellulose also prevented dissolution of the needles and absorbed up to 300% and 234% its own weight in water (8% and 12% w/w NC/FSBP), whereas FSBP films dissolved completely within 1 min, Indicating that the FSBP-NC films can be used to produce microneedles with prolonged dissolution rate. FTIR spectrometry of the FSBP films was compared with the FSBP-NC films and the NC gels. The FTIR showed typical peaks for fish scale polymer and nanocellulose with evidence of interactions. SEM micrographs showed relatively good dispersion of NC in FSBP at both NC contents corresponding to 8% and 12% w/w NC/FSBP respectively.

  8. Microneedles from Fishscale-Nanocellulose Blends Using Low Temperature Mechanical Press Method

    Directory of Open Access Journals (Sweden)

    Ololade Olatunji

    2015-09-01

    Full Text Available Fish scale biopolymer blended with nanocellulose crystals is used for production of microneedles applying mechanical press microfabrication and the effect of nanocellulose on microfabrication, water absorption, moisture stability and mechanical properties of the microneedles is reported. The results show that microneedles produced from the nanocellulose loaded fish scale biopolymer requires higher temperature for micromolding (80 ± 5 °C than microneedles from only fish scale biopolymer, which were moldable at 50 ± 5 °C. The mechanical properties of the fish scale biopolymer-nanocellulose (FSBP-NC films showed that the addition of nanocellulose (NC resulted in lower elongation and higher tensile stress compared to fish scale biopolymer (FSBP films. The nanocellulose also prevented dissolution of the needles and absorbed up to 300% and 234% its own weight in water (8% and 12% w/w NC/FSBP, whereas FSBP films dissolved completely within 1 min, Indicating that the FSBP-NC films can be used to produce microneedles with prolonged dissolution rate. FTIR spectrometry of the FSBP films was compared with the FSBP-NC films and the NC gels. The FTIR showed typical peaks for fish scale polymer and nanocellulose with evidence of interactions. SEM micrographs showed relatively good dispersion of NC in FSBP at both NC contents corresponding to 8% and 12% w/w NC/FSBP respectively.

  9. Solid Microneedles for Transdermal Delivery of Amantadine Hydrochloride and Pramipexole Dihydrochloride

    Directory of Open Access Journals (Sweden)

    Mylien T. Hoang

    2015-09-01

    Full Text Available The aim of this project was to study the influence of microneedles on transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride across porcine ear skin in vitro. Microchannel visualization studies were carried out and characterization of the microchannel depth was performed using confocal laser scanning microscopy (CLSM to demonstrate microchannel formation following microneedle roller application. We also report, for the first time, the use of TA.XT Plus Texture Analyzer to characterize burst force in pig skin for transdermal drug delivery experiments. This is the force required to rupture pig skin. The mean passive flux of amantadine hydrochloride, determined using a developed LC–MS/MS technique, was 22.38 ± 4.73 µg/cm2/h, while the mean flux following the use of a stainless steel microneedle roller was 49.04 ± 19.77 µg/cm2/h. The mean passive flux of pramipexole dihydrochloride was 134.83 ± 13.66 µg/cm2/h, while the flux following the use of a stainless steel microneedle roller was 134.04 ± 0.98 µg/cm2/h. For both drugs, the difference in flux values following the use of solid stainless steel microneedle roller was not statistically significantly (p > 0.05. Statistical analysis was carried out using the Mann–Whitney Rank sum test.

  10. Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque.

    Science.gov (United States)

    Edens, Chris; Dybdahl-Sissoko, Naomi C; Weldon, William C; Oberste, M Steven; Prausnitz, Mark R

    2015-09-08

    The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Dense vertical SU-8 microneedles drawn from a heated mold with precisely controlled volume

    International Nuclear Information System (INIS)

    Xiang, Zhuolin; Wang, Hao; Yen, Shih-Cheng; Lee, Chengkuo; Murugappan, Suresh Kanna; Pastorin, Giorgia

    2015-01-01

    Drawing lithography technology has recently become a popular technique to fabricate (3D) microneedles. The conventional drawing process shows some limitations in fabricating dense, scale-up and small microneedles. In this study, we demonstrate a new drawing lithography process from a self-loading mold which is able to overcome these challenges. Different from the conventional molds which have difficult alignment and loading issues, a released SU-8 membrane is attached onto a SU-8 coated wafer to generate an innovative self-loading mold. The physically distinct SU-8 colloid in this mold successfully avoids the merging of the microneedle tips in the drawing process. Meanwhile, the same SU-8 colloid in mold can provide microneedles with uniform lengths on a large surface area. Furthermore, a low temperature drawing process with this improved technique prevents sharp tips from bending during the solidification stage. Remarkably, this new drawing lithography technology can fabricate microneedles with various lengths and they are strong enough to penetrate the outermost skin layer, namely the stratum corneum. The spacing between two adjacent microneedles is optimized to maximize the penetration rate through the skin. Histology images and drug diffusion testing demonstrate that microchannels are successfully created and the drugs can permeate the tissue under the skin. The fabricated microneedles are demonstrated to deliver insulin in vivo and lower blood glucose levels, suggesting future possible applications for minimally invasive transdermal delivery of macromolecules. (paper)

  12. Modeling and flow analysis of piezoelectric based micropump with various shapes of microneedle

    Energy Technology Data Exchange (ETDEWEB)

    Haldkar, Rakesh Kumar; Gupta, Vijay Kumar; Sheorey, Tanuja [PDPM Indian Institute of Information Technology Design and Manufacturing Jabalpur, 482005 (India)

    2017-06-15

    Micropumps have been investigated as drug delivery and disease diagnostic devices. Many of these micropumps have been designed, considering primarily, available micro fabrication technologies rather than appropriate pump performance analysis. Piezoelectric and silicon based micro pumps are more popular as compared to other smart materials being explored. The microneedle is an integral part of these micropumps providing an interface between the drug reservoir and the patient’s body for extracting the blood for investigation. Blood collected in the pump chamber passes through the biosensor and gives the required investigation report. It is aimed to minimize the pain while the microneedle is inserted in the body without having any effect on the flow characteristics. Several factors affect the pain while inserting the needle, out of which shape and size of the microneedle are two important parameters. In this study we have investigated the effect of shape of the microneedle on the flow inside the micropump. A micropump design is based on the required flow at the biosensor point. All computations were carried out with water (Newtonian fluid) as the working fluid after carrying out a comparative analysis with human blood (non-Newtonian fluid). For the pentagonal shaped microneedle, the velocity at the top of the microneedle was minimum, which is beneficial in that fluid should remain in contact with the sensor for longer time.

  13. Modeling and flow analysis of piezoelectric based micropump with various shapes of microneedle

    International Nuclear Information System (INIS)

    Haldkar, Rakesh Kumar; Gupta, Vijay Kumar; Sheorey, Tanuja

    2017-01-01

    Micropumps have been investigated as drug delivery and disease diagnostic devices. Many of these micropumps have been designed, considering primarily, available micro fabrication technologies rather than appropriate pump performance analysis. Piezoelectric and silicon based micro pumps are more popular as compared to other smart materials being explored. The microneedle is an integral part of these micropumps providing an interface between the drug reservoir and the patient’s body for extracting the blood for investigation. Blood collected in the pump chamber passes through the biosensor and gives the required investigation report. It is aimed to minimize the pain while the microneedle is inserted in the body without having any effect on the flow characteristics. Several factors affect the pain while inserting the needle, out of which shape and size of the microneedle are two important parameters. In this study we have investigated the effect of shape of the microneedle on the flow inside the micropump. A micropump design is based on the required flow at the biosensor point. All computations were carried out with water (Newtonian fluid) as the working fluid after carrying out a comparative analysis with human blood (non-Newtonian fluid). For the pentagonal shaped microneedle, the velocity at the top of the microneedle was minimum, which is beneficial in that fluid should remain in contact with the sensor for longer time

  14. Modeling of transdermal drug delivery with a microneedle array

    Science.gov (United States)

    Lv, Y.-G.; Liu, J.; Gao, Y.-H.; Xu, B.

    2006-11-01

    Transdermal drug delivery is generally limited by the extraordinary barrier properties of the stratum corneum, the outer 10-15 µm layer of skin. A conventional needle inserted across this barrier and into deeper tissues could effectively deliver drugs. However, it would lead to infection and cause pain, thereby reducing patient compliance. In order to administer a frequent injection of insulin and other therapeutic agents more efficiently, integrated arrays with very short microneedles were recently proposed as very good candidates for painless injection or extraction. A variety of microneedle designs have thus been made available by employing the fabrication tools of the microelectronics industry and using materials such as silicon, metals, polymers and glass with feature sizes ranging from sub-micron to nanometers. At the same time, experiments were also made to test the capability of the microneedles to inject drugs into tissues. However, due to the difficulty encountered in measurement, a detailed understanding of the spatial and transient drug delivery process still remains unclear up to now. To better grasp the mechanisms involved, quantitative theoretical models were developed in this paper to simultaneously characterize the flow and drug transport, and numerical solutions were performed to predict the kinetics of dispersed drugs injected into the skin from a microneedle array. Calculations indicated that increasing the initial injection velocity and accelerating the blood circulation in skin tissue with high porosity are helpful to enhance the transdermal drug delivery. This study provides the first quantitative simulation of fluid injection through a microneedle array and drug species transport inside the skin. The modeling strategy can also possibly be extended to deal with a wider range of clinical issues such as targeted nanoparticle delivery for therapeutics or molecular imaging.

  15. Three-dimensional printing of a microneedle array on personalized curved surfaces for dual-pronged treatment of trigger finger.

    Science.gov (United States)

    Lim, Seng Han; Ng, Jian Yao; Kang, Lifeng

    2017-01-10

    The hand function of patients who suffer from trigger finger can be impaired by the use of traditional splints. There is also a risk of systemic side effects with oral non-steroidal anti-inflammatory drugs (NSAIDs) used for pain relief. Microneedle-assisted transdermal drug delivery offers an attractive alternative for local delivery of NSAIDs. However, traditional microneedle arrays fabricated on flat surfaces are unable to deliver drugs effectively across the undulating skin surface of affected finger(s). In this study, using 3D printing, a dual-function microneedle array has been fabricated on personalized curved surfaces (microneedle splint) for drug delivery and splinting of the affected finger. The novel microneedle splint was assessed for its physical characteristics and the microneedles were shown to withstand up to twice the average thumb force without fracturing. An average skin penetration efficiency of 64% on dermatomed human cadaver skin was achieved and the final microneedle splint showed biocompatibility with human dermal cell lines. A significantly higher amount of diclofenac permeated through the skin by 0.5 h with the use of the microneedle splint as compared to intact skin. The fabricated microneedle splint can thus be a potential new approach to treat trigger finger via personalized splinting without affecting normal hand function.

  16. Electroencephalogram measurement using polymer-based dry microneedle electrode

    Science.gov (United States)

    Arai, Miyako; Nishinaka, Yuya; Miki, Norihisa

    2015-06-01

    In this paper, we report a successful electroencephalogram (EEG) measurement using polymer-based dry microneedle electrodes. The electrodes consist of needle-shaped substrates of SU-8, a silver film, and a nanoporous parylene protective film. Differently from conventional wet electrodes, microneedle electrodes do not require skin preparation and a conductive gel. SU-8 is superior as a structural material to poly(dimethylsiloxane) (PDMS; Dow Corning Toray Sylgard 184) in terms of hardness, which was used in our previous work, and facilitates the penetration of needles through the stratum corneum. SU-8 microneedles can be successfully inserted into the skin without breaking and could maintain a sufficiently low skin-electrode contact impedance for EEG measurement. The electrodes successfully measured EEG from the frontal pole, and the quality of acquired signals was verified to be as high as those obtained using commercially available wet electrodes without any skin preparation or a conductive gel. The electrodes are readily applicable to record brain activities for a long period with little stress involved in skin preparation to the users.

  17. Microneedles for Transdermal Biosensing: Current Picture and Future Direction.

    Science.gov (United States)

    Ventrelli, Letizia; Marsilio Strambini, Lucanos; Barillaro, Giuseppe

    2015-12-09

    A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Successful application of large microneedle patches by human volunteers.

    Science.gov (United States)

    Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F

    2017-04-15

    We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600μm), were prepared from aqueous blends of 15% w/w Gantrez ® S97 and 7.5% w/w poly(ethyleneglycol) 10,000Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500μm. Ten human volunteers successfully self-inserted the microneedles of these larger patches in their skin, following appropriate instruction, as confirmed by transepidermal water loss measurements. The mean insertion depth ranged between 300 and 450μm over the area of the large patches. That this was not significantly different to a single unit MN patch self-applied by the same volunteers is encouraging. Microneedle patch sizes much larger than the 1-2cm 2 will be required if this technology is to be successfully translated to clinic for delivery of drug substances. The work described here suggests that use of such larger patches by patients can be successful, potentially opening up the possibility for a significant expansion of the size of the market for transdermal drug delivery. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  19. Enhanced delivery of hydrophilic peptides in vitro by transdermal microneedle pretreatment.

    Science.gov (United States)

    Zhang, Suohui; Qiu, Yuqin; Gao, Yunhua

    2014-02-01

    The aims of this study were to investigate the utility of solid microneedle arrays (150 µm in length) in enhancing transdermal delivery of peptides and to examine the relationship between peptide permeation rates and D2O flux. Four model peptides were used (Gly-Gln-Pro-Arg [tetrapeptide-3, 456.6 Da], Val-Gly-Val-Ala-Pro-Gly [hexapeptide, 498.6 Da], AC-Glu-Glu-Met-Gln-Arg-Arg-NH2 [acetyl hexapeptide-3, 889 Da] and Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 [oxytocin, 1007.2 Da]). The influence of microneedle pretreatment on skin permeation was evaluated using porcine ear skin with Franze diffusion cell. Peptide permeation across the skin was significantly enhanced by microneedle pretreatment, and permeation rates were dependent on peptide molecular weights. A positive correlation between D2O flux and acetyl hexapeptide-3 clearances suggests that convective solvent flow contributes to the enhanced transdermal peptide delivery. It is concluded that solid microneedle arrays are effective devices to enhance skin delivery of peptides.

  20. Enhanced delivery of hydrophilic peptides in vitro by transdermal microneedle pretreatment

    Directory of Open Access Journals (Sweden)

    Suohui Zhang

    2014-02-01

    Full Text Available The aims of this study were to investigate the utility of solid microneedle arrays (150 µm in length in enhancing transdermal delivery of peptides and to examine the relationship between peptide permeation rates and D2O flux. Four model peptides were used (Gly–Gln–Pro–Arg [tetrapeptide-3, 456.6 Da], Val–Gly–Val–Ala–Pro–Gly [hexapeptide, 498.6 Da], AC–Glu–Glu–Met–Gln–Arg–Arg–NH2 [acetyl hexapeptide-3, 889 Da] and Cys–Tyr–Ile–Gln–Asn–Cys–Pro–Leu–Gly–NH2 [oxytocin, 1007.2 Da]. The influence of microneedle pretreatment on skin permeation was evaluated using porcine ear skin with Franze diffusion cell. Peptide permeation across the skin was significantly enhanced by microneedle pretreatment, and permeation rates were dependent on peptide molecular weights. A positive correlation between D2O flux and acetyl hexapeptide-3 clearances suggests that convective solvent flow contributes to the enhanced transdermal peptide delivery. It is concluded that solid microneedle arrays are effective devices to enhance skin delivery of peptides.

  1. Microneedling as a successful treatment for alopecia X in two Pomeranian siblings.

    Science.gov (United States)

    Stoll, Steve; Dietlin, Christian; Nett-Mettler, Claudia S

    2015-10-01

    Alopecia X (hair cycle arrest) is a relatively frequent hair growth disorder in Pomeranians and several other breeds, characterized by symmetrical, noninflammatory alopecia without systemic signs. The cause and pathogenesis remain unknown. Previously reported treatments with various topical and systemic drugs have been variably successful. We hypothesized that superficial mechanical skin trauma applied with a microneedling device would induce long-term hair regrowth at treated sites. Two neutered female Pomeranian siblings with histologically confirmed alopecia X. Previous treatments with deslorelin, melatonin and topical minoxidil had failed to produce significant hair regrowth. The dogs were anaesthetized and the skin was punctured with a microneedling device. Dogs were followed over a period of 12 months. Five weeks after microneedling hair regrowth started, followed by a reduction in hyperpigmentation of affected skin. After 12 weeks there was a 90% improvement in coat coverage at previously alopecic areas. Twelve months after the procedure, coat conditions remained stable. No adverse effects were noted. This is the first report of microneedling to induce hair regrowth in dogs affected by alopecia X. Long-term studies with microneedling in a larger number of dogs with alopecia X will need to be performed to confirm these preliminary results and to further evaluate if hair-regrowth is permanent. © 2015 ESVD and ACVD.

  2. Micromolding for ceramic microneedle arrays

    NARCIS (Netherlands)

    van Nieuwkasteele-Bystrova, Svetlana Nikolajevna; Lüttge, Regina

    2011-01-01

    The fabrication process of ceramic microneedle arrays (MNAs) is presented. This includes the manufacturing of an SU-8/Si-master, its double replication resulting in a PDMS mold for production by micromolding and ceramic sintering. The robustness of the replicated structures was tested by means of

  3. Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch.

    Science.gov (United States)

    Quan, Fu-Shi; Kim, Yeu-Chun; Song, Jae-Min; Hwang, Hye Suk; Compans, Richard W; Prausnitz, Mark R; Kang, Sang-Moo

    2013-09-01

    Skin vaccination with influenza virus-like particles (VLPs) using microneedles has been shown to induce protection similar to or better than that induced by intramuscular immunization. In this study, we examined the long-term protective efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using microneedle patches coated with the vaccine. Microneedle vaccination of mice in the skin induced 100% protection against lethal challenge infection with influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus-specific total IgG response and hemagglutination inhibition (HAI) titers were maintained at high levels for over 1 year after microneedle vaccination. Microneedle vaccination also induced substantial levels of lung IgG and IgA antibody responses, and antibody-secreting plasma cells from spleen and bone marrow, as well as conferring effective control of lung viral loads, resulting in complete protection 14 months after vaccination. These strong and long-lasting immune responses were enabled in part by stabilization of the vaccine by formulation with trehalose during microneedle patch fabrication. Administration of the stabilized vaccine using microneedles was especially effective at enabling strong recall responses measured 4 days after lethal virus challenge, including increased HAI and antibody-secreting cells in the spleen and reduced viral titer and inflammatory response in the lung. The results in this study indicate that skin vaccination with VLP vaccine using a microneedle patch provides long-term protection against influenza in mice.

  4. Molybdenum coated SU-8 microneedle electrodes for transcutaneous electrical nerve stimulation.

    Science.gov (United States)

    Soltanzadeh, Ramin; Afsharipour, Elnaz; Shafai, Cyrus; Anssari, Neda; Mansouri, Behzad; Moussavi, Zahra

    2017-11-21

    Electrophysiological devices are connected to the body through electrodes. In some applications, such as nerve stimulation, it is needed to minimally pierce the skin and reach the underneath layers to bypass the impedance of the first layer called stratum corneum. In this study, we have designed and fabricated surface microneedle electrodes for applications such as electrical peripheral nerve stimulation. We used molybdenum for microneedle fabrication, which is a biocompatible metal; it was used for the conductive layer of the needle array. To evaluate the performance of the fabricated electrodes, they were compared with the conventional surface electrodes in nerve conduction velocity experiment. The recorded signals showed a much lower contact resistance and higher bandwidth in low frequencies for the fabricated microneedle electrodes compared to those of the conventional electrodes. These results indicate the electrode-tissue interface capacitance and charge transfer resistance have been increased in our designed electrodes, while the contact resistance decreased. These changes will lead to less harmful Faradaic current passing through the tissue during stimulation in different frequencies. We also compared the designed microneedle electrodes with conventional ones by a 3-dimensional finite element simulation. The results demonstrated that the current density in the deep layers of the skin and the directivity toward a target nerve for microneedle electrodes were much more than those for the conventional ones. Therefore, the designed electrodes are much more efficient than the conventional electrodes for superficial transcutaneous nerve stimulation purposes.

  5. Development of the novel coating formulations for skin vaccination using stainless steel microneedle.

    Science.gov (United States)

    Kim, Seong-Jin; Shin, Ju-Hyung; Noh, Jin-Yong; Song, Chang-Seon; Kim, Yeu-Chun

    2016-10-01

    This study focused on the development of novel coating formulations for stainless steel microneedles against influenza A virus. With in vitro studies, various viscosity enhancers and stabilizers were screened based on the hemagglutination activity of the vaccine, which was coated and dried onto a stainless steel chip at room temperature for 1 day. Following the long-term storage test, the hemagglutination activity and particle size of the vaccine, which was formulated with conventional or methylcellulose or hydroxyethyl cellulose and dried onto the microneedle, were monitored. Next, to evaluate the in vivo immunogenicity and protection effect of each dried vaccine formulation, mice were immunized by the antigen-coated microneedle, which had either the conventional or the proposed formulation. Two novel formulations were chosen in the preliminary screening, and in further evaluations, they exhibited a 20 % higher HA activity during storage for 3 months, and no aggregation was observed during storage after drying. In a mouse model, the microneedle with the novel formulation elicited a higher level of IgG and IgG2a was more prevalent in the IgG isotype profile. In addition, mice immunized with the HEC-coated microneedle survived with small weight loss (>90 %) against lethal challenge infection. Overall, the novel formulation hydroxyethyl cellulose preserved significantly higher HA activity during the production and storage of the microneedle as well as improved the in vivo immunogenicity of the vaccine.

  6. Intracellular Protein Delivery and Gene Transfection by Electroporation Using a Microneedle Electrode Array

    Science.gov (United States)

    Choi, Seong-O; Kim, Yeu-Chun; Lee, Jeong Woo; Park, Jung-Hwan

    2012-01-01

    The impact of many biopharmaceuticals, including protein- and gene-based therapies, has been limited by the need for better methods of delivery into cells within tissues. Here, we present intracellular delivery of molecules and transfection with plasmid DNA by electroporation using a novel microneedle electrode array designed for targeted treatment of skin and other tissue surfaces. The microneedle array is molded out of polylactic acid. Electrodes and circuitry required for electroporation are applied to the microneedle array surface by a new metal-transfer micromolding method. The microneedle array maintains mechanical integrity after insertion into pig cadaver skin and is able to electroporate human prostate cancer cells in vitro. Quantitative measurements show that increasing electroporation pulse voltage increases uptake efficiency of calcein and bovine serum albumin, whereas increasing pulse length has lesser effects over the range studied. Uptake of molecules by up to 50 % of cells and transfection of 12 % of cells with a gene for green fluorescent protein is demonstrated at high cell viability. We conclude that the microneedle electrode array is able to electroporate cells, resulting in intracellular uptake of molecules, and has potential applications to improve intracellular delivery of proteins, DNA and other biopharmaceuticals. PMID:22328093

  7. Analgesic Microneedle Patch for Neuropathic Pain Therapy.

    Science.gov (United States)

    Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Wang, Ji; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Yeomans, David C; Wu, Mei X; Xie, Xinmin Simon

    2017-01-24

    Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

  8. Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods

    OpenAIRE

    Vrdoljak, Anto; Allen, Evin A.; Ferrara, Francesca; Temperton, Nigel J.; Crean, Abina M.; Moore, Anne C.

    2016-01-01

    Dissolvable microneedle (DMN) patches for immunization have multiple benefits, including vaccine stability and ease-of-use. However, conventional DMN fabrication methods have several drawbacks. Here we describe a novel, microfluidic, drop dispensing-based dissolvable microneedle production method that overcomes these issues. Uniquely, heterogeneous arrays, consisting of microneedles of diverse composition, can be easily produced on the same patch. Robustness of the process was demonstrated by...

  9. STUDY & ANALYSIS OF MICRO NEEDLE MATERIAL BY ANSYS

    OpenAIRE

    Santosh Kumar Singh*, Prabhat Sinha, N.N. Singh, Nagendra Kumar

    2017-01-01

    In this research the concept of design and analysis, silicon and stainless steel based on hollow micro-needles for transdermal drug delivery(TDD) have been evaluated by Using ANSYS & computational fluid dynamic (CFD), structural. Micro fluidic analysis has performed to ensure the micro-needles design suitability for Drug delivery. The effect of axial and transverse load on single and micro-needle array has investigated with the mechanical properties of micro-needle. The analysis predicte...

  10. Comparison between the efficacy of microneedling combined with 5-fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo.

    Science.gov (United States)

    Mina, Mary; Elgarhy, Lamia; Al-Saeid, Hanan; Ibrahim, Zeinab

    2018-03-12

    Several treatment modalities had been used for the treatment of vitiligo, but the optimal treatment has not yet been identified. To study the efficacy of microneedling with 5-flurouracil vs its efficacy with tacrolimus in the treatment of vitiligo. Twenty-five patients with vitiligo were subjected to microneedling of 2 patches of vitiligo with dermapen, then application of 5-fluorouracil to 1 patch and tacrolimus on the other patch. This procedure was repeated every 2 weeks for every patient for maximum 6 months (12 sessions). The patients were followed up for 3 months after the last session. The overall repigmentation was significantly higher in 5-fluorouracil-treated patches compared with tacrolimus. Excellent improvement occurred in 48% of 5- flurouracil-treated patches while only in 16% of tacrolimus-treated patches. In the acral parts, 40% of the patches treated with 5-fluorouracil achieved excellent improvement (repigmentation >75%), while no patch in the acral parts achieved excellent improvement with tacrolimus. However, there was significant difference between the 2 drugs,regarding inflammation, ulceration, and hyperpigmentation which occurred with 5-fluorouracil. Microneedling combined with 5-fluorouracil or tacrolimus is safe and effective treatment of vitiligo. However, 5-fluorouracil achieved a greater percentage of repigmentation than tacrolimus particularly in the acral parts. © 2018 Wiley Periodicals, Inc.

  11. Design and modeling of microneedle integrated with microactuator for drug delivery

    Science.gov (United States)

    Girija Sravani, K.; Srinivas, Y.; Swain, Bikash; Sunil Banu, K.; Srinivasa Rao, K.

    2014-08-01

    Today's world has very much demand for the development of microscale devices, due to its less cost, space requirements, high-dimensional stability and especially manufacturing time. In this paper, we have design and simulated MEMS based microactuator and microneedle integration which will be very helpful for blood sampling device like e-mosquito. The dimensions of the modeled beam are of 100 mm long, 30 mm width, 10 mm thickness. This new design model consists of piezoceramic material sandwiched between two metal electrodes and the piezoelectric actuator is made with microneedle which will help for blood sampling purposes. The results after the simulation of this new model present that it will be suitable for blood sampling analysis with aluminum as electrodes and silicon as microneedle.

  12. Surface Replication of Molded Products with Microneedle Features in Injection Molding

    Science.gov (United States)

    Uchiumi, Kazuyasu; Takayama, Tetsuo; Ito, Hiroshi; Inou, Akinori

    Micro-molding of microneedle features was conducted using several injection-molding techniques. Injection compression molding and injection molding were performed with supercritical carbon dioxide fluid and with or without vacuum processing inside the mold cavity. Effects of process parameters on processability and surface replication of the molded parts were evaluated. The height replication ratio for microneedles was improved using injection compression molding. At a shorter compression stroke, the needle height was improved, and the influence of compression delay time was also small. Moreover, the effects of vacuum processing inside the mold cavity under the filling process were slight. The height replication ratio for microneedles showed the highest values using injection molding using supercritical carbon dioxide fluid with vacuum inside the mold cavity.

  13. Hollow proppants and a process for their manufacture

    Science.gov (United States)

    Jones, A.H.; Cutler, R.A.

    1985-10-15

    Hollow, fine-grained ceramic proppants are less expensive and improve fracture control when compared to conventional proppants (dense alumina, mullite, bauxite, zirconia, etc.). Hollow proppants of the present invention have been fabricated by spray drying, followed by sintering in order to obtain a dense case and a hollow core. These proppants generally have high sphericity and roundness (Krumbein sphericity and roundness greater than 0.8), have diameters on average between 2,250 and 125 [mu]m, depending on proppant size required, and have strength equal to or greater than that of sand. The hollow core, the size of which can be controlled, permits better fracture control in hydraulic fracturing treatments since the proppant can be transported in lower viscosity fluids. Hollow proppants produced at the same cost/weight as conventional proppants also provide for lower costs, since less weight is required to fill the same volume. The fine-grained (preferably less than 5 [mu]m in diameter) ceramic case provides the strength necessary to withstand closure stresses and prevent crushing. 6 figs.

  14. Controlled delivery of ropinirole hydrochloride through skin using modulated iontophoresis and microneedles.

    Science.gov (United States)

    Singh, Neha D; Banga, Ajay K

    2013-05-01

    The objective of this study was to investigate the effect of modulated current application using iontophoresis- and microneedle-mediated delivery on transdermal permeation of ropinirole hydrochloride. AdminPatch® microneedles and microchannels formed by them were characterized by scanning electron microscopy, dye staining and confocal microscopy. In vitro permeation studies were carried out using Franz diffusion cells, and skin extraction was used to quantify drug in underlying skin. Effect of microneedle pore density and ions in donor formulation was studied. Active enhancement techniques, continuous iontophoresis (74.13 ± 2.20 µg/cm(2)) and microneedles (66.97 ± 10.39 µg/cm(2)), significantly increased the permeation of drug with respect to passive delivery (8.25 ± 2.41 µg/cm(2)). Modulated iontophoresis could control the amount of drug delivered at a given time point with the highest flux being 5.12 ± 1.70 µg/cm(2)/h (5-7 h) and 5.99 ± 0.81 µg/cm(2)/h (20-22 h). Combination of modulated iontophoresis and microneedles (46.50 ± 6.46 µg/cm(2)) showed significantly higher delivery of ropinirole hydrochloride compared to modulated iontophoresis alone (84.91 ± 9.21 µg/cm(2)). Modulated iontophoresis can help in maintaining precise control over ropinirole hydrochloride delivery for dose titration in Parkinson's disease therapy and deliver therapeutic amounts over a suitable patch area and time.

  15. Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches.

    Science.gov (United States)

    Chu, Leonard Y; Ye, Ling; Dong, Ke; Compans, Richard W; Yang, Chinglai; Prausnitz, Mark R

    2016-04-01

    This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature. Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C. While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1-2 weeks outside of refrigeration, vaccine in microneedle patches lost 40-50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo. These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.

  16. The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Julia Nguyen

    2016-11-01

    Full Text Available The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h compared to passive delivery (12.83 ± 6.30 µg/cm2/h. For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h. Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

  17. Design of experiment characterization of microneedle fabrication processes based on dry silicon etching

    Science.gov (United States)

    Held, J.; Gaspar, J.; Ruther, P.; Hagner, M.; Cismak, A.; Heilmann, A.; Paul, O.

    2010-02-01

    This paper reports on the characterization of dry etching-based processes for the fabrication of silicon microneedles using a design of experiment (DoE) approach. The possibility of using such microneedles as protruding microelectrodes able to electroporate adherently growing cells and record intracellular potentials motivates the systematic analysis of the influence of etching parameters on the needle shape. Two processes are characterized: a fully isotropic etch process and a three-step etching approach. In the first case, the shape of the microneedles is defined by a single etch step. For the stepped method, the structures are realized using the following sequence: a first, isotropic step defines the tip; this is followed by anisotropic etching that increases the height of the needle; a final isotropic procedure thins the microneedle and sharpens its tip. From the various process parameters tested, it is concluded that the isotropic fabrication is influenced mostly by four process parameters, whereas six parameters dominantly govern the outcome of the stepped etching technique. The dependence of the needle shape on the etch mask diameter is also investigated. Microneedles with diameters down to the sub-micrometer range and heights below 10 µm are obtained. The experimental design is performed using the D-optimal method. The resulting geometry, i.e. heights, diameters and radii of curvature measured at different positions, is extracted from scanning electron micrographs of needle cross-sections obtained from cuts by focused ion beam. The process parameters are used as inputs and the geometry features of the microneedles as outputs for the analysis of the process.

  18. Design of experiment characterization of microneedle fabrication processes based on dry silicon etching

    International Nuclear Information System (INIS)

    Held, J; Gaspar, J; Ruther, P; Paul, O; Hagner, M; Cismak, A; Heilmann, A

    2010-01-01

    This paper reports on the characterization of dry etching-based processes for the fabrication of silicon microneedles using a design of experiment (DoE) approach. The possibility of using such microneedles as protruding microelectrodes able to electroporate adherently growing cells and record intracellular potentials motivates the systematic analysis of the influence of etching parameters on the needle shape. Two processes are characterized: a fully isotropic etch process and a three-step etching approach. In the first case, the shape of the microneedles is defined by a single etch step. For the stepped method, the structures are realized using the following sequence: a first, isotropic step defines the tip; this is followed by anisotropic etching that increases the height of the needle; a final isotropic procedure thins the microneedle and sharpens its tip. From the various process parameters tested, it is concluded that the isotropic fabrication is influenced mostly by four process parameters, whereas six parameters dominantly govern the outcome of the stepped etching technique. The dependence of the needle shape on the etch mask diameter is also investigated. Microneedles with diameters down to the sub-micrometer range and heights below 10 µm are obtained. The experimental design is performed using the D-optimal method. The resulting geometry, i.e. heights, diameters and radii of curvature measured at different positions, is extracted from scanning electron micrographs of needle cross-sections obtained from cuts by focused ion beam. The process parameters are used as inputs and the geometry features of the microneedles as outputs for the analysis of the process.

  19. Improvement of Transdermal Delivery of Exendin-4 Using Novel Tip-Loaded Microneedle Arrays Fabricated from Hyaluronic Acid.

    Science.gov (United States)

    Liu, Shu; Wu, Dan; Quan, Ying-Shu; Kamiyama, Fumio; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-01-04

    The purpose of this study was to evaluate the characteristics of exendin-4 tip-loaded microneedle arrays and to compare their acute efficacy with subcutaneous injections in type 2 diabetic GK/Slc rats. Fluorescein isothiocyanate labeled dextran with an average molecular weight of 4,000 (FD4) was selected as a model drug, and FD4 tip-loaded microneedle arrays were prepared in this study. In addition, intraperitoneal glucose tolerance tests after application of exendin-4 tip-loaded microneedle arrays were also compared with those after subcutaneous injection in type 2 diabetic GK/Slc rats. The release of FD4 from the tip-loaded microneedle arrays was very rapid, particularly in the initial 30 s, and most of the FD4 was released within 5 min. In addition, glucose tolerance was improved and the insulin secretion was enhanced after application of exendin-4 tip-loaded microneedle arrays, and these effects were comparable to those after subcutaneous injection of exendin-4. Similar plasma concentration profiles were seen after application of exendin-4 tip-loaded microneedle arrays, as was the case with subcutaneous injection in type 2 diabetic GK/Slc rats. These findings indicate that exendin-4 tip-loaded microneedle arrays can be used as an alternative to achieve sufficient delivery of exendin-4 for treatment of type 2 diabetes. To our knowledge, this is the first report of transdermal exendin-4 delivery using tip-loaded microneedle arrays.

  20. A microneedle patch containing measles vaccine is immunogenic in non-human primates.

    Science.gov (United States)

    Edens, Chris; Collins, Marcus L; Goodson, James L; Rota, Paul A; Prausnitz, Mark R

    2015-09-08

    Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify the logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID₅₀) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Injection moulded microneedle sensor for real-time wireless pH monitoring.

    Science.gov (United States)

    Mirza, Khalid B; Zuliani, Claudio; Hou, Benjamin; Ng, Fu Siong; Peters, Nicholas S; Toumazou, Christofer

    2017-07-01

    This paper describes the development of an array of individually addressable pH sensitive microneedles using injection moulding and their integration within a portable device for real-time wireless recording of pH distributions in biological samples. The fabricated microneedles are subjected to gold patterning followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of pH change. Miniaturised electronics suitable for the sensors readout, analog-to-digital conversion and wireless transmission of the potentiometric data are embodied within the device, enabling it to measure real-time pH of soft biological samples such as muscles. In this paper, real-time recording of the cardiac pH distribution, during ischemia followed by reperfusion cycles in cardiac muscles of male Wistar rats has been demonstrated by using the microneedle array.

  2. Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity.

    Science.gov (United States)

    Omolu, Abbie; Bailly, Maryse; Day, Richard M

    2017-11-01

    Many chronic wounds exhibit high matrix metalloproteinase (MMP) activity that impedes the normal wound healing process. Intradermal delivery (IDD) of sub-antimicrobial concentrations of doxycycline, as an MMP inhibitor, could target early stages of chronic wound development and inhibit further wound progression. To deliver doxycycline intradermally, the skin barrier must be disrupted. Microneedle rollers offer a minimally invasive technique to penetrate the skin by creating multiple microchannels that act as temporary conduits for drugs to diffuse through. In this study, an innovative and facile approach for delivery of doxycycline across Strat-M TM membrane was investigated using microneedle rollers. The quantity and rate of doxycycline diffusing through the micropores directly correlated with increasing microneedle lengths (250, 500 and 750 μm). Treatment of Strat-M TM with microneedle rollers resulted in a reduction in fibroblast-mediated collagen gel contraction and MMP activity compared with untreated Strat-M TM . Our results show that treatment of an epidermal mimetic with microneedle rollers provides sufficient permeabilization for doxycycline diffusion and inhibition of MMP activity. We conclude that microneedle rollers are a promising, clinically ready tool suitable for delivery of doxycycline intradermally to treat chronic wounds.

  3. Indirect rapid prototyping of antibacterial acid anhydride copolymer microneedles

    International Nuclear Information System (INIS)

    Boehm, Ryan D; Miller, Philip R; Singh, Ritika; Narayan, Roger J; Shah, Akash; Stafslien, Shane; Daniels, Justin

    2012-01-01

    Microneedles are needle-like projections with microscale features that may be used for transdermal delivery of a variety of pharmacologic agents, including antibacterial agents. In the study described in this paper, an indirect rapid prototyping approach involving a combination of visible light dynamic mask micro-stereolithography and micromolding was used to prepare microneedle arrays out of a biodegradable acid anhydride copolymer, Gantrez® AN 169 BF. Fourier transform infrared spectroscopy, energy dispersive x-ray spectrometry and nanoindentation studies were performed to evaluate the chemical and mechanical properties of the Gantrez® AN 169 BF material. Agar plating studies were used to evaluate the in vitro antimicrobial performance of these arrays against Bacillus subtilis, Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Large zones of growth inhibition were noted for Escherichia coli, S. aureus, Enterococcus faecalis and B. subtilis. The performance of Gantrez® AN 169 BF against several bacteria suggests that biodegradable acid anhydride copolymer microneedle arrays prepared using visible light dynamic mask micro-stereolithography micromolding may be useful for treating a variety of skin infections. (communication)

  4. Adenosine-loaded dissolving microneedle patches to improve skin wrinkles, dermal density, elasticity and hydration.

    Science.gov (United States)

    Kang, G; Tu, T N T; Kim, S; Yang, H; Jang, M; Jo, D; Ryu, J; Baek, J; Jung, H

    2018-04-01

    Although dissolving microneedle patches have been widely studied in the cosmetics field, no comparisons have been drawn with the topical applications available for routine use. In this study, two wrinkle-improving products, adenosine-loaded dissolving microneedle patches and an adenosine cream, were evaluated for efficacy, with respect to skin wrinkling, dermal density, elasticity, and hydration, and safety in a clinical test on the crow's feet area. Clinical efficacy and safety tests were performed for 10 weeks on 22 female subjects with wrinkles around their eyes. The adenosine-loaded dissolving microneedle patch was applied once every 3 days, in the evening, for 8 weeks to the designated crow's feet area. The adenosine cream was applied two times per day, in the morning and evening, for 8 weeks to the other crow's feet area. Skin wrinkling, dermal density, elasticity, and hydration were measured by using PRIMOS ® premium, Dermascan ® C, Cutometer ® MPA580, and Corneometer ® CM 825, respectively. In addition, subjective skin irritation was evaluated by self-observation, and objective skin irritation was assessed through expert interviews. The adenosine-loaded dissolving microneedle patches had a similar or better efficacy than the adenosine cream. Both groups showed statistically significant efficacy for almost all parameters (P hydration efficacy (P skin-improvement parameters, adenosine-loaded dissolving microneedle patches showed the same or better effect than the adenosine cream, although the weekly adenosine dose was 140 times lower. The dissolving microneedle patches caused no adverse reactions. These adenosine-loaded dissolving microneedle patches are expected to be safe, effective, and novel cosmetics for skin improvement. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  5. Characterization of silicon isotropic etch by inductively coupled plasma etcher for microneedle array fabrication

    International Nuclear Information System (INIS)

    Ji, J; Tay, F E H; Miao Jianmin; Sun Jianbo

    2006-01-01

    This work investigates the isotropic etching properties in inductively coupled plasma (ICP) etcher for microneedle arrays fabrication. The effects of process variables including powers, gas and pressure on needle structure generation are characterized by factorial design of experiment (DOE). The experimental responses of vertical etching depth, lateral etching length, ratio of vertical etching depth to lateral etching length and photoresist etching rate are reported. The relevance of the etching variables is also presented. The obtained etching behaviours for microneedle structure generation will be applied to develop recipes to fabricate microneedles in designed dimensions

  6. Characterization of silicon isotropic etch by inductively coupled plasma etcher for microneedle array fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Ji, J [Mechanical Engineering National University of Singapore, 119260, Singapore (Singapore); Tay, F E H [Mechanical Engineering National University of Singapore, 119260, Singapore (Singapore); Miao Jianmin [MicroMachines Center, School of Mechanical and Aerospace Engineering, Nanyang Technologica l University, 50 Nanyang Avenue, 639798 (Singapore); Sun Jianbo [MicroMachines Center, School of Mechanical and Aerospace Engineering, Nanyang Technologica l University, 50 Nanyang Avenue, 639798 (Singapore)

    2006-04-01

    This work investigates the isotropic etching properties in inductively coupled plasma (ICP) etcher for microneedle arrays fabrication. The effects of process variables including powers, gas and pressure on needle structure generation are characterized by factorial design of experiment (DOE). The experimental responses of vertical etching depth, lateral etching length, ratio of vertical etching depth to lateral etching length and photoresist etching rate are reported. The relevance of the etching variables is also presented. The obtained etching behaviours for microneedle structure generation will be applied to develop recipes to fabricate microneedles in designed dimensions.

  7. Use of a monopolar microneedle device in a transconjunctival, retroseptal approach.

    Science.gov (United States)

    Gander, Thomas; Rostetter, Claudio; Blumer, Michael; Wagner, Maximilian; Schumann, Paul; Wiedemeier, Daniel B; Rücker, Martin; Essig, Harald

    2017-12-01

    Transconjunctival approach is a standard procedure to address fractures of orbit and the infraorbital rim. Modifications such as transcaruncular or lateral canthal widening allow for extended orbital wall exposure. Especially concerning aesthetics, the transconjunctival approach shows benefits compared to the transcutaneous incisions, such as the transciliary and infraorbital access. Moreover, transconjunctival approach is favored in the literature concerning lid retraction. Monopolar devices have become popular in surgery in the past decades because of good depth control and simultaneous hemostasis with consequently improved overview. Also numerous surgeons use monopolar device in orbital surgery, their safety have never been proved. In this study monopolar microneedle device is compared with conventional access by scalpel concerning lid retraction, foreign body sensation and formation of symblepharon. In our collective complication rates were comparable between the scalpel and the microneedle group. The monopolar microneedle device shows favorable results compared with the scalpel and is easy to handle. Weather the conventional access by scalpel or the access by monopolar device is selected, is rather driven by the surgeon's preferences than by statistical relevance. Nevertheless, monopolar microneedle device shows better depth control and simplifies readaptation of the conjunctival wound's margin. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  8. Microneedle-based drug delivery systems for transdermal route.

    Science.gov (United States)

    Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

    2014-03-01

    Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

  9. Optimization of impedance spectroscopy techniques for measuring cutaneous micropore formation after microneedle treatment in an elderly population.

    Science.gov (United States)

    Kelchen, Megan N; Holdren, Grant O; Farley, Matthew J; Zimmerman, M Bridget; Fairley, Janet A; Brogden, Nicole K

    2014-12-01

    The objective of this study was to optimize a reproducible impedance spectroscopy method in elderly subjects as a means to evaluate the effects of microneedles on aging skin. Human volunteers were treated with microneedles at six sites on the upper arm. Repeated impedance measurements were taken pre- and post-microneedle insertion. Two electrode types were evaluated (dry vs. gel), using either light or direct pressure to maintain contact between the electrode and skin surface. Transepidermal water loss (TEWL) was measured as a complementary technique. Five control subjects and nine elderly subjects completed the study. Microneedle insertion produced a significant decrease in impedance from baseline in all subjects (p micropore formation. This was supported by a complementary significant increase in TEWL (p micropore formation in elderly subjects, which will be essential for future studies describing microneedle-assisted transdermal delivery in aging populations.

  10. Delivery of Methotrexate and Characterization of Skin Treated by Fabricated PLGA Microneedles and Fractional Ablative Laser.

    Science.gov (United States)

    Nguyen, Hiep X; Banga, Ajay K

    2018-02-21

    This study investigated in vitro transdermal delivery of methotrexate through dermatomed porcine ear and cadaver human skin treated with poly (D,L-lactide-co-glycolide) acid microneedles or fractional ablative laser. PLGA microneedles were fabricated and characterized using scanning electron microscopy and mechanical assessment techniques. The integrity of treated skin was evaluated by rheometer, transepidermal water loss, and skin electrical resistance measurements. Successful skin microporation was demonstrated by dye binding, histology, pore uniformity, confocal laser microscopy, and DermaScan studies. In vitro permeation experiment was performed on Franz diffusion cells to determine drug delivery into and across the skin. Both physical treatments resulted in a considerable decrease in skin resistance and an increase in transepidermal water loss value. The laser-created microchannels were significantly larger than those formed by microneedles (p < 0.05). An effective force of 41.04 ± 18.33 N was required to achieve 100% penetration efficiency of the microneedles. For both porcine ear and human skin, laser ablation provided a significantly higher methotrexate permeability into the receptor chamber and skin layers compared to microneedle poration and untreated skin (p < 0.05). Both fractional ablative laser and polymeric microneedles markedly enhanced in vitro transdermal delivery of methotrexate into and across skin. Graphical Abstract ᅟ.

  11. Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice.

    Science.gov (United States)

    van der Maaden, Koen; Varypataki, Eleni Maria; Romeijn, Stefan; Ossendorp, Ferry; Jiskoot, Wim; Bouwstra, Joke

    2014-10-01

    The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the coated arrays onto ex vivo human skin, and by conducting a dermal immunization study in mice. The release of antigen into ex vivo human skin from the coated microneedles was determined by using radioactively labeled ovalbumin. To investigate the induction of antigen-specific IgG, and CD4(+) and CD8(+) T-cell responses, BALB/c mice were immunized with antigen-coated pH-sensitive microneedles by the 'coat and poke' approach. These responses were compared to responses induced by the 'poke and patch' approach, and subcutaneous and intradermal vaccination with classic hypodermic needles. The pH-sensitive microneedle arrays were efficiently coated with ovalbumin (95% coating efficiency) and upon application of six microneedle arrays 4.27 of 7 μg ovalbumin was delivered into the skin, showing a release efficiency of 70%. In contrast, the 'poke and patch' approach led to a delivery of only 6.91 of 100 μg ovalbumin (7% delivery efficiency). Immunization by means of ovalbumin-coated microneedles resulted in robust CD4(+) and CD8(+) T-cell responses comparable to those obtained after subcutaneous or intradermal immunization with conventional needles. Moreover, it effectively induced IgG responses; however, it required prime-boost immunizations before antibodies were produced. In conclusion, antigen delivery into ex vivo human skin by antigen-coated pH-sensitive microneedle arrays is more efficient than the 'poke-and-patch' approach and in vivo vaccination studies show the applicability of pH-sensitive microneedles for the induction of both T cell and B cell responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Youssef W. Naguib

    2014-02-01

    Full Text Available Topical 5-fluorouracil (5-FU is approved for the treatment of superficial basal cell carcinoma and actinic keratosis. However, 5-FU suffers from poor skin permeation. Microneedles have been successfully applied to improve the skin permeability of small and large molecules, and even nanoparticles, by creating micron-sized pores in the stratum corneum layer of the skin. In this report, the feasibility of using microneedles to increase the skin permeability of 5-FU was tested. Using full thickness mouse skin mounted on Franz diffusion apparatus, it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles (500 μm in length, 50 μm in base diameter. In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space, the antitumor activity of a commercially available 5-FU topical cream (5% was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles, as compared to when the cream was simply applied on a skin area, underneath which the tumor cells were implanted, and without pretreatment of the skin with microneedles. Fluorouracil is not approved for melanoma therapy, but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.

  13. Efficacy and safety of a novel, soluble microneedle patch for the improvement of facial wrinkle.

    Science.gov (United States)

    Hong, Ji Yeon; Ko, Eun Jung; Choi, Sun Young; Li, Kapsok; Kim, A Reum; Park, Jin O; Kim, Beom Joon

    2018-04-01

    Various kinds of functional cosmetics are on the market, although there are a variety of opinions concerning the actual effect. Transdermal microneedle patch has been introduced as a newly developed device for drug delivery through the skin. This study was conducted to verify the face skin improvement effect and safety of a novel cosmetic microneedle patch. A total of 84 Korean females finished this prospective clinical trial. The subjects were divided into 3 groups: (1) soluble hyaluronic acid (HA) microneedle patch alone, (2) soluble HA microneedle patch plus adenosine wrinkle cream, and (3) adenosine wrinkle cream alone. The treatments were applied to the crow's feet and nasolabial fold wrinkle for 12 weeks. The test areas were measured before treatment and at 4, 8, and 12 weeks after use of the test product. At the completion of the testing period of the trial, the global assessment of efficacy and product preferences were surveyed from the subjects. Combination treatment with wrinkle cream and microneedle patch significantly improved Merz scale for crow's feet and nasolabial folds, compared to the sole application of wrinkle cream or patch. Measurement on the crow's feet showed an overall improvement in all 3 groups, yielding no significant differences among the groups. No serious adverse effects were observed during the follow-up period. Combination application of a soluble microneedle patch and wrinkle cream was an effective treatment in improving facial wrinkles, thus enhancing skin rejuvenation. © 2017 Wiley Periodicals, Inc.

  14. Characterization of polymeric microneedle arrays for transdermal drug delivery.

    Directory of Open Access Journals (Sweden)

    Yusuf K Demir

    Full Text Available Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS, where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN precision was ranging from ± 0.18 to ± 1.82% for microneedle height, ± 0.45 to ± 1.42% for base diameter, and ± 0.22 to ± 0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.

  15. Mechanisms of sampling interstitial fluid from skin using a microneedle patch.

    Science.gov (United States)

    Samant, Pradnya P; Prausnitz, Mark R

    2018-05-01

    Although interstitial fluid (ISF) contains biomarkers of physiological significance and medical interest, sampling of ISF for clinical applications has made limited impact due to a lack of simple, clinically useful techniques that collect more than nanoliter volumes of ISF. This study describes experimental and theoretical analysis of ISF transport from skin using microneedle (MN) patches and demonstrates collection of >1 µL of ISF within 20 min in pig cadaver skin and living human subjects using an optimized system. MN patches containing arrays of submillimeter solid, porous, or hollow needles were used to penetrate superficial skin layers and access ISF through micropores (µpores) formed upon insertion. Experimental studies in pig skin found that ISF collection depended on transport mechanism according to the rank order diffusion sampling is transport through the dermis. Based on these studies and other considerations like safety and convenience for future clinical use, we designed an MN patch prototype to sample ISF using suction as the driving force. Using this approach, we collected ISF from human volunteers and identified the presence of biomarkers in the collected ISF. In this way, sampling ISF from skin using an MN patch could enable collection of ISF for use in research and medicine.

  16. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

    Science.gov (United States)

    Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

    2014-08-21

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

  17. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

    Science.gov (United States)

    Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

    2014-01-01

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

  18. In vivo visualization of microneedle conduits in human skin using laser scanning microscopy

    International Nuclear Information System (INIS)

    Bal, S; Kruithof, A C; Bouwstra, J; Liebl, H; Tomerius, M; Lademann, J; Meinke, M

    2010-01-01

    Solid microneedles enhance the penetration of drugs into the viable skin but little is known about the geometry of the conduits in vivo. Therefore, laser scanning microscopy was used to visualize the conduits of a microneedle system with needles at a length of 300 μm in 6 healthy subjects over a period of time. The model drug, a fluorescent dye was applied before and after piercing. Laser scanning microscopy was evaluated as being an excellent method to monitor the geometry and closure of the conduits over time. The used microneedle system was evaluated as suitable to enhance the transport of model drugs into the viable epidermis without bleeding and a short closure time of the conduits at the skin surface

  19. In vivo visualization of microneedle conduits in human skin using laser scanning microscopy

    Science.gov (United States)

    Bal, S.; Kruithof, A. C.; Liebl, H.; Tomerius, M.; Bouwstra, J.; Lademann, J.; Meinke, M.

    2010-03-01

    Solid microneedles enhance the penetration of drugs into the viable skin but little is known about the geometry of the conduits in vivo. Therefore, laser scanning microscopy was used to visualize the conduits of a microneedle system with needles at a length of 300 μm in 6 healthy subjects over a period of time. The model drug, a fluorescent dye was applied before and after piercing. Laser scanning microscopy was evaluated as being an excellent method to monitor the geometry and closure of the conduits over time. The used microneedle system was evaluated as suitable to enhance the transport of model drugs into the viable epidermis without bleeding and a short closure time of the conduits at the skin surface.

  20. Fabrication of polymeric hollow nanospheres, hollow nanocubes and hollow plates

    Science.gov (United States)

    Cheng, Daming; Xia, Haibing; Chan, Hardy Sze On

    2006-03-01

    A facile strategy for fabricating polypyrrole-chitosan (PPy-CS) hollow nanostructures with different shapes (sphere, cube and plate) and a wide range of sizes (from 35 to 600 nm) is described. These hollow structures have been fabricated using silver bromide as a single template material for polymer nucleation and growth. PPy-CS hollow nanostructures are formed by reaction with an etching agent to remove the core. These hollow nanostructures have been extensively characterized using various techniques such as TEM, FT-IR, UV-vis, and XRD.

  1. Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch

    Science.gov (United States)

    Kim, Yeu-Chun; Song, Jae-Min; Lipatov, Aleksandr S.; Choi, Seong-O; Lee, Jeong Woo; Donis, Ruben O.; Compans, Richard W.; Kang, Sang-Moo; Prausnitz, Mark R.

    2012-01-01

    Effective public health responses to an influenza pandemic require an effective vaccine that can be manufactured and administered to large populations in the shortest possible time. In this study, we evaluated a method for vaccination against avian influenza virus that uses a DNA vaccine for rapid manufacturing and delivered by a microneedle skin patch for simplified administration and increased immunogenicity. We prepared patches containing 700 µm-long microneedles coated with an avian H5 influenza hemagglutinin DNA vaccine from A/Viet Nam/1203/04 influenza virus. The coating DNA dose increased with DNA concentration in the coating solution and the number of dip coating cycles. Coated DNA was released into the skin tissue by dissolution within minutes. Vaccination of mice using microneedles induced higher levels of antibody responses and hemagglutination inhibition titers, and improved protection against lethal infection with avian influenza as compared to conventional intramuscular delivery of the same dose of the DNA vaccine. Additional analysis showed that the microneedle coating solution containing carboxymethylcellulose and a surfactant may have negatively affected the immunogenicity of the DNA vaccine. Overall, this study shows that DNA vaccine delivery by microneedles can be a promising approach for improved vaccination to mitigate an influenza pandemic. PMID:22504442

  2. Optimization of HNA etching parameters to produce high aspect ratio solid silicon microneedles

    International Nuclear Information System (INIS)

    Hamzah, A A; Yeop Majlis, B; Yunas, J; Dee, C F; Abd Aziz, N; Bais, B

    2012-01-01

    High aspect ratio solid silicon microneedles with a concave conic shape were fabricated. Hydrofluoric acid–nitric acid–acetic acid (HNA) etching parameters were characterized and optimized to produce microneedles that have long and narrow bodies with smooth surfaces, suitable for transdermal drug delivery applications. The etching parameters were characterized by varying the HNA composition, the optical mask's window size, the etching temperature and bath agitation. An L9 orthogonal Taguchi experiment with three factors, each having three levels, was utilized to determine the optimal fabrication parameters. Isoetch contours for HNA composition with 0% and 10% acetic acid concentrations were presented and a high nitric acid region was identified to produce microneedles with smooth surfaces. It is observed that an increase in window size indiscriminately increases the etch rate in both the vertical and lateral directions, while an increase in etching temperature beyond 35 °C causes the etching to become rapid and uncontrollable. Bath agitation and sample placement could be manipulated to achieve a higher vertical etch rate compared to its lateral counterpart in order to construct high aspect ratio microneedles. The Taguchi experiment performed suggests that a HNA composition of 2:7:1 (HF:HNO 3 :CH 3 COOH), window size of 500 µm and agitation rate of 450 RPM are optimal. Solid silicon microneedles with an average height of 159.4 µm, an average base width of 110.9 µm, an aspect ratio of 1.44, and a tip angle and diameter of 19.2° and 0.38 µm respectively were successfully fabricated. (paper)

  3. Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

    Science.gov (United States)

    An, Myunggi; Liu, Haipeng

    2017-07-01

    Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Evaluation of microneedling fractional radiofrequency device for treatment of acne scars

    Directory of Open Access Journals (Sweden)

    Byalekere Shivanna Chandrashekar

    2014-01-01

    Full Text Available Background: Various treatment modalities including non-invasive methods such as chemical peels, topical retinoids, microdermabrasion, minimally invasive techniques such as microneedling, fractional lasers, microneedling radiofrequency devices and invasive procedures such as acne scar surgeries and ablative lasers are used for acne scars, each with its own unique advantages and disadvantages. This study is a retrospective assessment of efficacy and safety of microneedling fractional radiofrequency in the treatment of acne scars. Methods: Thirty one patients of skin types III-V with moderate and severe facial acne scarring received four sequential fractional radiofrequency treatments over a period of 6 months with an interval of 6 weeks between each session. Goodman & Baron′s acne scar grading system was used for assessment by a side by side comparison of preoperative and post- operative photographs taken at their first visit and at the end of 3 months after the last session. Results: Estimation of improvement with Goodman and Baron′s Global Acne Scarring System showed that by qualitative assessment of 31 patients with grade 3 and grade 4 acne scars, 80.64% showed improvement by 2 grades and 19.35% showed improvement by 1 grade. Quantitative assessment showed that 58% of the patients had moderate, 29% had minimal, 9% had good and 3% showed very good improvement. Adverse effects were limited to transient pain, erythema, edema and hyperpigmentation. Conclusion: Microneedling fractional radiofrequency is efficacious for the treatment of moderate and severe acne scars.

  5. A Microneedle Functionalized with Polyethyleneimine and Nanotubes for Highly Sensitive, Label-Free Quantification of DNA.

    Science.gov (United States)

    Saadat-Moghaddam, Darius; Kim, Jong-Hoon

    2017-08-16

    The accurate measure of DNA concentration is necessary for many DNA-based biological applications. However, the current methods are limited in terms of sensitivity, reproducibility, human error, and contamination. Here, we present a microneedle functionalized with polyethyleneimine (PEI) and single-walled carbon nanotubes (SWCNTs) for the highly sensitive quantification of DNA. The microneedle was fabricated using ultraviolet (UV) lithography and anisotropic etching, and then functionalized with PEI and SWCNTs through a dip coating process. The electrical characteristics of the microneedle change with the accumulation of DNA on the surface. Current-voltage measurements in deionized water were conducted to study these changes in the electrical properties of the sensor. The sensitivity test found the signal to be discernable from the noise level down to 100 attomolar (aM), demonstrating higher sensitivity than currently available UV fluorescence and UV absorbance based methods. A microneedle without any surface modification only had a 100 femtomolar (fM) sensitivity. All measurement results were consistent with fluorescence microscopy.

  6. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  7. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses.

    Science.gov (United States)

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E

    2014-05-15

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  8. Microneedle fractional radiofrequency increases epidermal hyaluronan and reverses age-related epidermal dysfunction.

    Science.gov (United States)

    Lee, Hee Jung; Seo, Seong Rak; Yoon, Moon Soo; Song, Ji-Ye; Lee, Eun Young; Lee, Sang Eun

    2016-02-01

    Skin aging results in physiological alterations in keratinocyte activities and epidermal function, as well as dermal changes. Yet, the cellular and molecular mechanisms that cause epidermal dysfunction during skin aging are not well understood. Recently, the role of epidermal hyaluronan (HA) as an active regulator of dynamic cellular processes is getting attention and alterations in HA metabolism are thought to be important in age-related epidermal dysfunction. Microneedle fractional radiofrequency (RF) has shown effects for improving cutaneous aging. However, little is known about the effects of fractional RF on the epidermal HA and epidermal function. We investigated the effect of microneedle fractional RF on the expression of epidermal HA in young and aged mice epidermis. We performed fractional RF on the dorsal skin of 30 8-week-old (young) hairless mice and 15 47-week-old (aged) C57BL/6J mice. Skin samples were collected on day 1, 3, and 7. HA content was measured by ELISA. Gene expressions of CD 44, HABP4, and HAS3 were measured using real time RT-PCR. Immunohistochemistry for detection of HA, CD44, PCNA, and filaggrin were performed. HA content and the mRNA levels of HABP4, CD44, and HAS3 were upregulated in the epidermis of both young and aged mice after microneedle fractional RF treatment. The expression was increased from day 1 after treatment and increased expression persisted on day 7. Fractional RF treatment significantly increased PCNA and filaggrin expression only in the aged mice skin. Microneedle fractional RF increased epidermal HA and CD44 expression in both young and aged mice and reversed age-related epidermal dysfunction especially in aged mice, suggesting a new mechanism involved in the skin rejuvenation effect of microneedle fractional RF. © 2015 Wiley Periodicals, Inc.

  9. Nanoporous Microneedle Arrays Effectively Induce Antibody Responses against Diphtheria and Tetanus Toxoid

    Science.gov (United States)

    de Groot, Anne Marit; Platteel, Anouk C. M.; Kuijt, Nico; van Kooten, Peter J. S.; Vos, Pieter Jan; Sijts, Alice J. A. M.; van der Maaden, Koen

    2017-01-01

    The skin is immunologically very potent because of the high number of antigen-presenting cells in the dermis and epidermis, and is therefore considered to be very suitable for vaccination. However, the skin’s physical barrier, the stratum corneum, prevents foreign substances, including vaccines, from entering the skin. Microneedles, which are needle-like structures with dimensions in the micrometer range, form a relatively new approach to circumvent the stratum corneum, allowing for minimally invasive and pain-free vaccination. In this study, we tested ceramic nanoporous microneedle arrays (npMNAs), representing a novel microneedle-based drug delivery technology, for their ability to deliver the subunit vaccines diphtheria toxoid (DT) and tetanus toxoid (TT) intradermally. First, the piercing ability of the ceramic (alumina) npMNAs, which contained over 100 microneedles per array, a length of 475 µm, and an average pore size of 80 nm, was evaluated in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed in vitro. It was shown that DT and TT were successfully loaded into the tips of the ceramic nanoporous microneedles, and by using near-infrared fluorescently labeled antigens, we found that DT and TT were released following piercing of the antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT- and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen-specific antibodies, with titers similar to those obtained upon subcutaneous immunization with a similar dose. In conclusion, we show for the first time, the potential of npMNAs for intradermal (ID) immunization with subunit vaccines, which opens possibilities for future ID vaccination designs. PMID:29375544

  10. Nanoporous Microneedle Arrays Effectively Induce Antibody Responses against Diphtheria and Tetanus Toxoid.

    Science.gov (United States)

    de Groot, Anne Marit; Platteel, Anouk C M; Kuijt, Nico; van Kooten, Peter J S; Vos, Pieter Jan; Sijts, Alice J A M; van der Maaden, Koen

    2017-01-01

    The skin is immunologically very potent because of the high number of antigen-presenting cells in the dermis and epidermis, and is therefore considered to be very suitable for vaccination. However, the skin's physical barrier, the stratum corneum, prevents foreign substances, including vaccines, from entering the skin. Microneedles, which are needle-like structures with dimensions in the micrometer range, form a relatively new approach to circumvent the stratum corneum, allowing for minimally invasive and pain-free vaccination. In this study, we tested ceramic nanoporous microneedle arrays (npMNAs), representing a novel microneedle-based drug delivery technology, for their ability to deliver the subunit vaccines diphtheria toxoid (DT) and tetanus toxoid (TT) intradermally. First, the piercing ability of the ceramic (alumina) npMNAs, which contained over 100 microneedles per array, a length of 475 µm, and an average pore size of 80 nm, was evaluated in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed in vitro . It was shown that DT and TT were successfully loaded into the tips of the ceramic nanoporous microneedles, and by using near-infrared fluorescently labeled antigens, we found that DT and TT were released following piercing of the antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT- and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen-specific antibodies, with titers similar to those obtained upon subcutaneous immunization with a similar dose. In conclusion, we show for the first time, the potential of npMNAs for intradermal (ID) immunization with subunit vaccines, which opens possibilities for future ID vaccination designs.

  11. Nanoporous Microneedle Arrays Effectively Induce Antibody Responses against Diphtheria and Tetanus Toxoid

    Directory of Open Access Journals (Sweden)

    Anne Marit de Groot

    2017-12-01

    Full Text Available The skin is immunologically very potent because of the high number of antigen-presenting cells in the dermis and epidermis, and is therefore considered to be very suitable for vaccination. However, the skin’s physical barrier, the stratum corneum, prevents foreign substances, including vaccines, from entering the skin. Microneedles, which are needle-like structures with dimensions in the micrometer range, form a relatively new approach to circumvent the stratum corneum, allowing for minimally invasive and pain-free vaccination. In this study, we tested ceramic nanoporous microneedle arrays (npMNAs, representing a novel microneedle-based drug delivery technology, for their ability to deliver the subunit vaccines diphtheria toxoid (DT and tetanus toxoid (TT intradermally. First, the piercing ability of the ceramic (alumina npMNAs, which contained over 100 microneedles per array, a length of 475 µm, and an average pore size of 80 nm, was evaluated in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed in vitro. It was shown that DT and TT were successfully loaded into the tips of the ceramic nanoporous microneedles, and by using near-infrared fluorescently labeled antigens, we found that DT and TT were released following piercing of the antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT- and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen-specific antibodies, with titers similar to those obtained upon subcutaneous immunization with a similar dose. In conclusion, we show for the first time, the potential of npMNAs for intradermal (ID immunization with subunit vaccines, which opens possibilities for future ID vaccination designs.

  12. Microneedle and mucosal delivery of influenza vaccines

    Science.gov (United States)

    Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

    2017-01-01

    In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

  13. Bacillus Calmette-Guérin Vaccination Using a Microneedle Patch

    Science.gov (United States)

    Hiraishi, Yasuhiro; Nandakumar, Subhadra; Choi, Seong-O; Lee, Jeong Woo; Kim, Yeu-Chun; Posey, James E.; Sable, Suraj B.; Prausnitz, Mark R.

    2011-01-01

    Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be a leading cause of mortality among bacterial diseases, and the bacillus Calmette-Guerin (BCG) is the only licensed vaccine for human use against this disease. TB prevention and control would benefit from an improved method of BCG vaccination that simplifies logistics and eliminates dangers posed by hypodermic needles without compromising immunogenicity. Here, we report the design and engineering of a BCG-coated microneedle vaccine patch for a simple and improved intradermal delivery of the vaccine. The microneedle vaccine patch induced a robust cell-mediated immune response in both the lungs and spleen of guinea pigs. The response was comparable to the traditional hypodermic needle based intradermal BCG vaccination and was characterized by a strong antigen specific lymphocyte proliferation and IFN-γ levels with high frequencies of CD4+IFN-γ+, CD4+TNF-α+ and CD4+IFN-γ+TNF-α+ T cells. The BCG-coated microneedle vaccine patch was highly immunogenic in guinea pigs and supports further exploration of this new technology as a simpler, safer, and compliant vaccination that could facilitate increased coverage, especially in developing countries that lack adequate healthcare infrastructure. PMID:21277407

  14. Rapid prototyping of biodegradable microneedle arrays by integrating CO2 laser processing and polymer molding

    International Nuclear Information System (INIS)

    Tu, K T; Chung, C K

    2016-01-01

    An integrated technology of CO 2 laser processing and polymer molding has been demonstrated for the rapid prototyping of biodegradable poly-lactic-co-glycolic acid (PLGA) microneedle arrays. Rapid and low-cost CO 2 laser processing was used for the fabrication of a high-aspect-ratio microneedle master mold instead of conventional time-consuming and expensive photolithography and etching processes. It is crucial to use flexible polydimethylsiloxane (PDMS) to detach PLGA. However, the direct CO 2 laser-ablated PDMS could generate poor surfaces with bulges, scorches, re-solidification and shrinkage. Here, we have combined the polymethyl methacrylate (PMMA) ablation and two-step PDMS casting process to form a PDMS female microneedle mold to eliminate the problem of direct ablation. A self-assembled monolayer polyethylene glycol was coated to prevent stiction between the two PDMS layers during the peeling-off step in the PDMS-to-PDMS replication. Then the PLGA microneedle array was successfully released by bending the second-cast PDMS mold with flexibility and hydrophobic property. The depth of the polymer microneedles can range from hundreds of micrometers to millimeters. It is linked to the PMMA pattern profile and can be adjusted by CO 2 laser power and scanning speed. The proposed integration process is maskless, simple and low-cost for rapid prototyping with a reusable mold. (paper)

  15. Rapid prototyping of biodegradable microneedle arrays by integrating CO2 laser processing and polymer molding

    Science.gov (United States)

    Tu, K. T.; Chung, C. K.

    2016-06-01

    An integrated technology of CO2 laser processing and polymer molding has been demonstrated for the rapid prototyping of biodegradable poly-lactic-co-glycolic acid (PLGA) microneedle arrays. Rapid and low-cost CO2 laser processing was used for the fabrication of a high-aspect-ratio microneedle master mold instead of conventional time-consuming and expensive photolithography and etching processes. It is crucial to use flexible polydimethylsiloxane (PDMS) to detach PLGA. However, the direct CO2 laser-ablated PDMS could generate poor surfaces with bulges, scorches, re-solidification and shrinkage. Here, we have combined the polymethyl methacrylate (PMMA) ablation and two-step PDMS casting process to form a PDMS female microneedle mold to eliminate the problem of direct ablation. A self-assembled monolayer polyethylene glycol was coated to prevent stiction between the two PDMS layers during the peeling-off step in the PDMS-to-PDMS replication. Then the PLGA microneedle array was successfully released by bending the second-cast PDMS mold with flexibility and hydrophobic property. The depth of the polymer microneedles can range from hundreds of micrometers to millimeters. It is linked to the PMMA pattern profile and can be adjusted by CO2 laser power and scanning speed. The proposed integration process is maskless, simple and low-cost for rapid prototyping with a reusable mold.

  16. Use of Drawing Lithography-Fabricated Polyglycolic Acid Microneedles for Transdermal Delivery of Itraconazole to a Human Basal Cell Carcinoma Model Regenerated on Mice

    Science.gov (United States)

    Zhang, Jennifer; Wang, Yan; Jin, Jane Y.; Degan, Simone; Hall, Russell P.; Boehm, Ryan D.; Jaipan, Panupong; Narayan, Roger J.

    2016-04-01

    Itraconazole is a triazole agent that is routinely used for treatment of nail infections and other fungal infections. Recent studies indicate that itraconazole can also inhibit the growth of basal cell carcinoma (BCC) through suppression of the Sonic Hedgehog (SHH) signaling pathway. In this study, polyglycolic acid microneedle arrays and stainless steel microneedle arrays were used for transdermal delivery of itraconazole to a human BCC model which was regenerated on mice. One-by-four arrays of 642- μm-long polyglycolic acid microneedles with sharp tips were prepared using injection molding and drawing lithography. Arrays of 85 stainless steel 800- μm-tall microneedles attached to syringes were obtained for comparison purposes. Skin grafts containing devitalized split-thickness human dermis that had been seeded with human keratinocytes transduced to express human SHH protein were sutured to the skin of immunodeficient mice. Mice with this human BCC model were treated daily for 2 weeks with itraconazole dissolved in 60% dimethylsulfoxane and 40% polyethylene glycol-400 solution; transdermal administration of the itraconazole solution was facilitated by either four 1 × 4 polyglycolic acid microneedle arrays or stainless steel microneedle arrays. The epidermal tissues treated with polyglycolic acid microneedles or stainless steel microneedles were markedly thinner than that of the control (untreated) graft tissue. These preliminary results indicate that microneedles may be used to facilitate transdermal delivery of itraconazole for localized treatment of BCC.

  17. A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue

    Science.gov (United States)

    Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.

    2013-04-01

    Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here inspired by the endoparasite Pomphorhynchus laevis, which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~3.5-fold increase in adhesion strength compared with staples in skin graft fixation, and removal force of ~4.5 N cm-2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

  18. Microneedle technology for immunisation: Perception, acceptability and suitability for paediatric use.

    Science.gov (United States)

    Marshall, Sarah; Sahm, Laura J; Moore, Anne C

    2016-02-03

    To examine published research which explores the perception and acceptability of microneedle technology for immunisation and to investigate the suitability of this technology for paediatric use. A series of keywords and their synonyms were combined in various combinations and permutations using Boolean operators to sequentially search four databases (PubMed, Web of Science, Embase and CINAHL). Following removal of duplications and irrelevant results, 12 research articles were included in the final literature review. The opinions of patients, parents, children and healthcare professionals (HCP) were collated. A positive perception and a high level of acceptability predominated. Microneedle technology research has been focussed on demonstrating efficacy with minimal focus on determining HCP/public perception and acceptability for paediatric use, exemplified by the paucity of studies presented in this review. Commercial viability will depend on HCP/public acceptability of microneedle technology. An effort must be made to identify the barriers to acceptance and to overcome them by increasing awareness and education in stakeholder groups pertaining to the paediatric population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Microneedle crystals of cyano-substituted thiophene/phenylene co-oligomer epitaxially grown on KCl surface

    Science.gov (United States)

    Torii, Kazuki; Dokiya, Shohei; Tanaka, Yosuke; Yoshinaga, Shohei; Yanagi, Hisao

    2017-06-01

    A cyno-substituted thiophene/phenylene co-oligomer (TPCO), 5,5‧-bis(4‧-cyanobiphenyl-4-yl)-2,2‧-bithiophene (BP2T-CN), is vapor-deposited on KCl (001) surface kept at 220 °C by the mask-shadowing method. Transmission electron microscopy and fluorescence microscopy reveal that the deposited BP2T-CN crystallizes in two types of morphologies: microneedles and thin film crystallites. In particular, the predominant microneedles epitaxially grow in four directions in the manner that the BP2T-CN molecules align along the [110]KCl or [-110]KCl. X-ray diffraction patterns indicate that the BP2T-CN molecules in the microneedle lie parallel while those in the thin film crystallite obliquely stand on the KCl surface.

  20. Effect of Tension and Curvature of Skin on Insertion Characteristics of Microneedle Array

    Science.gov (United States)

    Tachikawa, Hiroto; Takano, Naoki; Nishiyabu, Kazuaki; Miki, Norihisa; Ami, Yoshimichi

    Recent MEMS (micro electro mechanical system) fabrication techniques have made it possible to produce painless microneedles precisely enough to be inserted into epidermis layer penetrating the stratum corneum of human skin. This paper presents a testing procedure to evaluate the insertion characteristics of microneedle array using cultured human skin considering the tension and the curvature. First, the biaxial strain applied to the cultured human skin was measured by optical technique with image processing. It was found that almost constant strain could be successfully given within a certain area and that error factors in the experiment except the thickness variation of the cultured skin were negligible. Next, using a microneedle square array for brain machine interface (BMI) application, the effects of biaxial tension and the curvature on insertion characteristics were discussed. Within the above mentioned area with high strain, the needles were successfully inserted.

  1. Randomized trial of electrodynamic microneedle combined with 5% minoxidil topical solution for the treatment of Chinese male Androgenetic alopecia.

    Science.gov (United States)

    Bao, Linlin; Gong, Lin; Guo, Menger; Liu, Taoming; Shi, Anyu; Zong, Haifeng; Xu, Xuegang; Chen, Hongduo; Gao, Xinghua; Li, Yuanhong

    2017-10-13

    In treating androgenetic alopecia, 5% minoxidil is a commonly used topical drug. By using electrodynamic microneedle at the same time may increase absorption of minoxidil and further stimulate hair growth. A 24-week, randomized, evaluator blinded, comparative study was performed to evaluate the efficacy of treating Chinese male androgenetic alopecia using microneedle combined with 5% minoxidil topical solution. Randomized subjects received topical 5% minoxidil (group 1, n = 20), local electrodynamic microneedle treatments (group 2, n = 20), or local electrodynamic microneedle treatments plus topical 5% minoxidil (group 3, n = 20). A total of 12 microneedle treatments were performed every 2 weeks with 2ml 5% minoxidil delivery in group 3 during each microneedle treatment. Patient receiving topical 5% minoxidil applied 1 ml of the solution twice daily over the course of the study. A total of 60 Chinese male subjects with Norwood-Hamilton type III-VI androgenetic alopecia were treated. The mean improvement in total hair density from baseline to 24 weeks was 18.8/cm 2 in group 1, 23.4/cm 2 in group 2, and 38.3/cm 2 in group 3. The hair growth in the 3 groups was significantly different (P = 0.002), but there were no significant differences in toxicity found between the 3 groups. Treatment with microneedle plus topical 5% minoxidil was associated with the best hair growth.

  2. Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment of Actinic Keratoses: A Randomized Clinical Trial.

    Science.gov (United States)

    Petukhova, Tatyana A; Hassoun, Lauren A; Foolad, Negar; Barath, Mayanka; Sivamani, Raja K

    2017-07-01

    Photodynamic therapy (PDT) is an effective and cosmetically favorable treatment modality for actinic keratoses (AKs). However, prolonged incubation times and pain associated with treatment are burdensome to the patient and a hindrance to widespread use of PDT as standard field therapy for AK. To evaluate efficacy and pain associated with microneedle expedited PDT. The Microneedle Photodynamic Therapy II (MNPDT-II) study was a randomized, single-blinded, split-face controlled, 2-arm clinical trial. Thirty-three participants with AK on the face were recruited in a university dermatology outpatient clinic from 2015 to 2016, and 32 participants completed the study. Participants were randomized into 2 incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA) incubation times, after pretreatment with a microneedle roller (200 um) vs a sham roller. They were blinded to the laterality of microneedle and sham roller assignments. After incubation, they were exposed to blue light (Blu-U, Dusa Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm2. The primary outcome was to quantitatively measure AK resolution, and the secondary outcome was to assess pain associated with microneedle pretreatment. Thirty-three individuals were recruited and randomized to either the 20-minute or the 10-minute incubation arm. Thirty-two participants completed the study with a mean follow-up time of 34.5 days in the 20-minute group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm, average AK clearance was 76% vs 58% on the sham side (P microneedle and sham sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK clearance for the microneedle pretreated side was 43% compared with 38% on the sham side (P = .66). Pain during the blue light exposure was not significantly different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21), respectively. Photodynamic therapy with microneedle pretreatment at

  3. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    Directory of Open Access Journals (Sweden)

    Kevin Ita

    2015-06-01

    Full Text Available Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

  4. DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system.

    Science.gov (United States)

    Cole, Grace; Ali, Ahlam A; McCrudden, Cian M; McBride, John W; McCaffrey, Joanne; Robson, Tracy; Kett, Vicky L; Dunne, Nicholas J; Donnelly, Ryan F; McCarthy, Helen O

    2018-03-03

    Dissolvable microneedles can be employed to deliver DNA to antigen presenting cells within the skin. However, this technology faces two main challenges: the poor transfection efficacy of pDNA following release from the microneedle matrix, and the limited loading capacity of the micron-scale devices. Two-tier delivery systems combining microneedle platforms and DNA delivery vectors have increased efficacy but the challenge of increasing the loading capacity remains. This study utilised lyophilisation to increase the loading of RALA/pDNA nanoparticles within dissolvable PVA microneedles. As a result, delivery was significantly enhanced in vivo into an appropriate range for DNA vaccination (∼50 μg per array). Furthermore, modifying the manufacturing process was not detrimental to the microneedle mechanical properties or cargo functionality. It was demonstrated that arrays retained mechanical and functional stability over short term storage, and were able to elicit gene expression in vitro and in vivo. Finally, treatment with this novel formulation significantly retarded the growth of established tumours, and proved superior to standard intramuscular injection in a preclinical model of cervical cancer. Copyright © 2018. Published by Elsevier B.V.

  5. Fabrication of a Microneedle/CNT Hierarchical Micro/Nano Surface Electrochemical Sensor and Its In-Vitro Glucose Sensing Characterization

    Directory of Open Access Journals (Sweden)

    Youngsam Yoon

    2013-12-01

    Full Text Available We report fabrication of a microneedle-based three-electrode integrated electrochemical sensor and in-vitro characterization of this sensor for glucose sensing applications. A piece of silicon was sequentially dry and wet etched to form a 15 × 15 array of tall (approximately 380 µm sharp silicon microneedles. Iron catalyst was deposited through a SU-8 shadow mask to form the working electrode and counter electrode. A multi-walled carbon nanotube forest was grown directly on the silicon microneedle array and platinum nano-particles were electrodeposited. Silver was deposited on the Si microneedle array through another shadow mask and chlorinated to form a Ag/AgCl reference electrode. The 3-electrode electrochemical sensor was tested for various glucose concentrations in the range of 3~20 mM in 0.01 M phosphate buffered saline (PBS solution. The sensor’s amperometric response to the glucose concentration is linear and its sensitivity was found to be 17.73 ± 3 μA/mM-cm2. This microneedle-based sensor has a potential to be used for painless diabetes testing applications.

  6. Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods.

    Science.gov (United States)

    Vrdoljak, Anto; Allen, Evin A; Ferrara, Francesca; Temperton, Nigel J; Crean, Abina M; Moore, Anne C

    2016-03-10

    Dissolvable microneedle (DMN) patches for immunization have multiple benefits, including vaccine stability and ease-of-use. However, conventional DMN fabrication methods have several drawbacks. Here we describe a novel, microfluidic, drop dispensing-based dissolvable microneedle production method that overcomes these issues. Uniquely, heterogeneous arrays, consisting of microneedles of diverse composition, can be easily produced on the same patch. Robustness of the process was demonstrated by incorporating and stabilizing adenovirus and MVA vaccines. Clinically-available trivalent inactivated influenza vaccine (TIV) in DMN patches is fully stable for greater than 6months at 40°C. Immunization using low dose TIV-loaded DMN patches induced significantly higher antibody responses compared to intramuscular-based immunization in mice. TIV-loaded patches also induced a broader, heterosubtypic neutralizing antibody response. By addressing issues that will be faced in large-scale fill-finish DMN fabrication processes and demonstrating superior thermostable characteristics and immunogenicity, this study progresses the translation of this microneedle platform to eventual clinical deployment. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Treatment of Décolletage Photoaging With Fractional Microneedling Radiofrequency.

    Science.gov (United States)

    Lyons, Alexis; Roy, Jillian; Herrmann, Jennifer; Chipps, Lisa

    2018-01-01

    The objective of this study was to examine the efficacy and safety of a novel fractional microneedling radiofrequency device to improve the appearance of rhytides and skin laxity of the décolletage. Twelve subjects received a total of three fractional microneedling radiofrequency treatments with Endymed Intensif (EndyMed Ltd., Cesarea, Israel) at least three weeks apart. Primary outcome measure was clinical efficacy quantified by a patient survey to assess treatment satisfaction as well as a physician Global Aesthetic Improvement Scale (GAIS). Photos were taken before every treatment and at a follow-up appointment. Assessments by two board-certified dermatologists revealed an overall improvement in 67% of patients. Seventy percent of subjects rated their post-treatment skin laxity and rhytides as improved, while 60% of patients rated their skin texture as improved. Eighty percent of subjects were at least slightly satisfied with their treatment. Forty percent of subjects would recommend this treatment to others. Subjects in this study demonstrated an overall improvement in décolletage appearance in regard to skin tightening, wrinkles, and skin texture suggested by overall patient satisfaction (80%) and physician-rated GAIS improvement (67%). This study suggests that fractional microneedling radiofrequency devices are a safe and efficacious way to improve overall décolletage appearance with little down time. J Drugs Dermatol. 2018;17(1):74-76..

  8. Multiplexed and Switchable Release of Distinct Fluids from Microneedle Platforms via Conducting Polymer Nanoactuators for Potential Drug Delivery

    Science.gov (United States)

    Valdés-Ramírez, Gabriela; Windmiller, Joshua R.; Claussen, Jonathan C.; Martinez, Alexandra G.; Kuralay, Filiz; Zhou, Ming; Zhou, Nandi; Polsky, Ronen; Miller, Philip R.; Narayan, Roger; Wang, Joseph

    2013-01-01

    We report on the development of a microneedle-based multiplexed drug delivery actuator that enables the controlled delivery of multiple therapeutic agents. Two individually-addressable channels on a single microneedle array, each paired with its own reservoir and conducting polymer nanoactuator, are used to deliver various permutations of two unique chemical species. Upon application of suitable redox potentials to the selected actuator, the conducting polymer is able to undergo reversible volume changes, thereby serving to release a model chemical agent in a controlled fashion through the corresponding microneedle channels. Time-lapse videos offer direct visualization and characterization of the membrane switching capability and, along with calibration investigations, confirm the ability of the device to alternate the delivery of multiple reagents from individual microneedles of the array with higher precision and temporal resolution than conventional drug delivery actuators. Analytical modeling offers prediction of the volumetric flow rate through a single microneedle and accordingly can be used to assist in the design of subsequent microneedle arrays. The robust solid-state design and lack of mechanical components circumvent reliability issues that challenge fragile conventional microelectromechanical drug delivery devices. This proof-of-concept study demonstrates the potential of the drug delivery actuator system to aid in the rapid administration of multiple therapeutic agents and indicates the potential to counteract diverse biomedical conditions. PMID:24174709

  9. Combination of microneedling and glycolic acid peels for the treatment of acne scars in dark skin.

    Science.gov (United States)

    Sharad, Jaishree

    2011-12-01

      Acne scars can cause emotional and psychosocial disturbance to the patient. Various modalities have been used for the treatment of acne scars like punch excision, subcision, peels, microdermabrasion, unfractionated and fractioned lasers. The latest in the treatment armamentarium is microneedling. Acne scars commonly coexist with postinflammatory hyperpigmentation. A combination of microneedling and glycolic acid (GA) peels was found to give excellent results in the treatment of such scars. The aim was to study the efficacy of a combination of microneedling with glycolic peel for the treatment of acne scars in pigmented skin.   Thirty patients in the age group of 20-40 years with atrophic box type or rolling scars with postinflammatory hyperpigmentation were chosen for the study. Two groups were made. The first group comprised of 30 patients in whom only microneedling was performed once in 6 weeks for five sessions. In the second group of 30 patients, a combination of microneedling and 35% GA peels was carried out. Patients from both groups were evaluated on the basis of Echelle d'Evaluation clinique des Cicatrices d'acné classification.   Based on the objective scoring and its statistical analysis, there was significant improvement in superficial and moderately deep scars (grade 1-3). There was also improvement in skin texture, reduction in postacne pigmentation in the second group.   Microneedling is a simple, inexpensive office procedure with no downtime. It is safe in Indian skin (skin types III-IV). The combined sequential treatment with GA peel caused a significant improvement in the acne scars without increasing morbidity. © 2011 Wiley Periodicals, Inc.

  10. Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

    Science.gov (United States)

    Zhao, Ji-Hui; Zhang, Qi-Bo; Liu, Bao; Piao, Xiang-Hua; Yan, Yu-Lu; Hu, Xiao-Ge; Zhou, Kuan; Zhang, Yong-Tai; Feng, Nian-Ping

    2017-01-01

    To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

  11. Microneedle delivery of trivalent influenza vaccine to the skin induces long-term cross-protection.

    Science.gov (United States)

    Kim, Yeu-Chun; Lee, Su-Hwa; Choi, Won-Hyung; Choi, Hyo-Jick; Goo, Tae-Won; Lee, Ju-Hie; Quan, Fu-Shi

    2016-12-01

    A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (p skin vaccination with trivalent vaccine using a microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.

  12. Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Karthik Nair

    2015-10-01

    Full Text Available Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA.

  13. Response to microneedling treatment in men with androgenetic alopecia who failed to respond to conventional therapy

    Directory of Open Access Journals (Sweden)

    Rachita Dhurat

    2015-01-01

    Full Text Available Introduction: The efficacy of conventional therapy viz. finasteride and minoxidil in androgenetic alopecia (AGA that is based on both preventing hair loss and promoting new hair growth, varies between 30% and 60%. This has led to a large number of patients unsatisfied who demand for a better cosmetic coverage over the scalp. Microneedling has recently been reported to be promising, effective and a safe treatment modality in the treatment of AGA. This augments the response of conventional therapy. Materials and Methods: Four men with AGA were on finasteride and 5% minoxidil solution since 2 to 5 years. Though there was no worsening in their respective AGA stages with the therapy, they showed no new hair growth. They were subjected to microneedling procedure over a period of 6 months along with their ongoing therapy. Patients were assessed with the use of the standardized 7-point evaluation scale and patients′ subjective hair growth assessment scale. The patients were followed up for 18 months post microneedling procedure to assess the sustainability of the response. Results: All patients showed a response of + 2 to + 3 on standardized 7-point evaluation scale. The response in the form of new hair growth started after 8-10 sessions. The patients′ satisfaction was more than 75% in three patients and more 50% in one patient, on patients′ subjective hair growth assessment scale. The obtained results were sustained post procedure during 18 months follow-up period. Conclusion : Treatment with microneedling showed an accelerated response with addition of microneedling procedure leading to significant scalp density. This is the first case series to report the boosting effect of microneedling with respect to new hair follicle stimulation in patients with androgenetic alopecia who were poor responders to conventional therapy.

  14. Hydrogel-forming microneedles prepared from "super swelling" polymers combined with lyophilised wafers for transdermal drug delivery.

    Directory of Open Access Journals (Sweden)

    Ryan F Donnelly

    Full Text Available We describe, for the first time, hydrogel-forming microneedle arrays prepared from "super swelling" polymeric compositions. We produced a microneedle formulation with enhanced swelling capabilities from aqueous blends containing 20% w/w Gantrez S-97, 7.5% w/w PEG 10,000 and 3% w/w Na2CO3 and utilised a drug reservoir of a lyophilised wafer-like design. These microneedle-lyophilised wafer compositions were robust and effectively penetrated skin, swelling extensively, but being removed intact. In in vitro delivery experiments across excised neonatal porcine skin, approximately 44 mg of the model high dose small molecule drug ibuprofen sodium was delivered in 24 h, equating to 37% of the loading in the lyophilised reservoir. The super swelling microneedles delivered approximately 1.24 mg of the model protein ovalbumin over 24 h, equivalent to a delivery efficiency of approximately 49%. The integrated microneedle-lyophilised wafer delivery system produced a progressive increase in plasma concentrations of ibuprofen sodium in rats over 6 h, with a maximal concentration of approximately 179 µg/ml achieved in this time. The plasma concentration had fallen to 71±6.7 µg/ml by 24 h. Ovalbumin levels peaked in rat plasma after only 1 hour at 42.36±17.01 ng/ml. Ovalbumin plasma levels then remained almost constant up to 6 h, dropping somewhat at 24 h, when 23.61±4.84 ng/ml was detected. This work represents a significant advancement on conventional microneedle systems, which are presently only suitable for bolus delivery of very potent drugs and vaccines. Once fully developed, such technology may greatly expand the range of drugs that can be delivered transdermally, to the benefit of patients and industry. Accordingly, we are currently progressing towards clinical evaluations with a range of candidate molecules.

  15. Electrical Impedance Spectroscopy for Detection of Cells in Suspensions Using Microfluidic Device with Integrated Microneedles

    Directory of Open Access Journals (Sweden)

    Muhammad Asraf Mansor

    2017-02-01

    Full Text Available In this study, we introduce novel method of flow cytometry for cell detection based on impedance measurements. The state of the art method for impedance flow cytometry detection utilizes an embedded electrode in the microfluidic to perform measurement of electrical impedance of the presence of cells at the sensing area. Nonetheless, this method requires an expensive and complicated electrode fabrication process. Furthermore, reuse of the fabricated electrode also requires an intensive and tedious cleaning process. Due to that, we present a microfluidic device with integrated microneedles. The two microneedles are placed at the half height of the microchannel for cell detection and electrical measurement. A commercially-available Tungsten needle was utilized for the microneedles. The microneedles are easily removed from the disposable PDMS (Polydimethylsiloxane microchannel and can be reused with a simple cleaning process, such as washing by ultrasonic cleaning. Although this device was low cost, it preserves the core functionality of the sensor, which is capable of detecting passing cells at the sensing area. Therefore, this device is suitable for low-cost medical and food safety screening and testing process in developing countries.

  16. Information transfer using wearable thin electrotactile displays with microneedle electrodes

    Science.gov (United States)

    Tezuka, Mayuko; Kitamura, Norihide; Miki, Norihisa

    2016-06-01

    Tactile sensation is considered as a promising information transfer tool that can replace or compensate for sight and hearing information. In this study, we developed a sheet-type electrotactile display with microneedle electrodes. This flexible and thin display is suitable for wearable applications. It can present tactile sensation to the skin at a low voltage by penetrating the stratum corneum with microneedles. As a proof-of-concept experiment of transferring information via tactile sensation, we first tried to convey signals of two patterns using a single display. Next, we attempted to use multiple displays and experimentally investigated the spatial resolution of the tactile sensation on the forearm. Finally, 3-bit information was successfully transferred by three devices attached to the forearm.

  17. A Microneedle Functionalized with Polyethyleneimine and Nanotubes for Highly Sensitive, Label-Free Quantification of DNA

    OpenAIRE

    Saadat-Moghaddam, Darius; Kim, Jong-Hoon

    2017-01-01

    The accurate measure of DNA concentration is necessary for many DNA-based biological applications. However, the current methods are limited in terms of sensitivity, reproducibility, human error, and contamination. Here, we present a microneedle functionalized with polyethyleneimine (PEI) and single-walled carbon nanotubes (SWCNTs) for the highly sensitive quantification of DNA. The microneedle was fabricated using ultraviolet (UV) lithography and anisotropic etching, and then functionalized w...

  18. Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

    Directory of Open Access Journals (Sweden)

    Zhao JH

    2017-07-01

    Full Text Available Ji-Hui Zhao,1,* Qi-Bo Zhang,1,* Bao Liu,2 Xiang-Hua Piao,1 Yu-Lu Yan,1 Xiao-Ge Hu,1 Kuan Zhou,1 Yong-Tai Zhang,1 Nian-Ping Feng1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Anethesiology Department, Augusta University, Augusta, GA, USA *These authors contributed equally to this work Purpose: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA was combined with platycodin (PD, a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array.Methods: OVA- and PD-loaded liposomes (OVA-PD-Lipos were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs, and hemolytic activity to rabbit red blood cells (RBCs were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated.Results: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin.Conclusion: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant. Keywords: subunit vaccine, saponin adjuvant, liposomes, dissolving microneedle array, intradermal vaccination

  19. Microneedles as Enhancer of Drug Absorption Through the Skin and Applications in Medicine and Cosmetology.

    Science.gov (United States)

    Serrano-Castañeda, Pablo; Escobar-Chavez, Jose Juan; Rodriguez-Cruz, Isabel Marlen; Melgoza, Luz Maria; Martinez-Hernandez, Jessica

    2018-01-01

    The microneedles technology has found applications in many health-related fields. For example, their application in drugs and vaccines delivery as well, as the determination of biomarkers, has been reported. They also have a place in the dermatology and cosmetic areas such as the treatment of wounds from burns, scars, acne, depigmentation, and alopecia will be shown. Microneedles are used in therapeutic applications and are manufactured using materials such as metal (steel, titanium, nickel), polymer (oly-glycolic acid (PGA), poly-lactide-co-glycolide acid (PLGA), poly-L-lactic acid (PLA), chitosan), glass, silicon, ceramic, carbohydrates (trehalose, sucrose, mannitol). Examples of application of microneedles and their advantages and disadvantages are discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  20. Efficacy and safety of a new microneedle patch for skin brightening: A Randomized, split-face, single-blind study.

    Science.gov (United States)

    Park, Kui Young; Kwon, Hyun Jung; Lee, Changjin; Kim, Daegun; Yoon, Jun Jin; Kim, Myeong Nam; Kim, Beom Joon

    2017-09-01

    Although microneedles are one of the best transdermal drug delivery systems for active compounds, few clinical trials have examined the safety and efficacy of brightening microneedle patches. To determine the efficacy and safety of a newly developed whitening microneedle patch. A split-face study was designed for efficacy assessment with 34 Korean women applying the tested product (a whitening microneedle patch) on one cheek and a control whitening essence on the other. We objectively measured changes in melanin index values and skin brightness by mexameter and chromameter. Each participant also used global assessment to determine skin whitening. In addition, 55 participants were selected for primary skin irritation tests and repeated insult patch tests for safety assessments. Mean skin brightness and melanin indexes improved (Pmicroneedle patch was effective and safe for skin brightening and would be a promising functional cosmetic product. © 2017 Wiley Periodicals, Inc.

  1. Microneedle array design determines the induction of protective memory CD8+ T cell responses induced by a recombinant live malaria vaccine in mice.

    Directory of Open Access Journals (Sweden)

    John B Carey

    Full Text Available Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC, must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+ T cell responses to a malaria antigen induced by a live vaccine.Recombinant modified vaccinia virus Ankara (MVA expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes.This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+ T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids

  2. Skin penetration enhancement by a microneedle device (Dermaroller) in vitro

    DEFF Research Database (Denmark)

    Badran, M M; Kuntsche, Judith; Fahr, A

    2009-01-01

    compared with an aqueous solution. Elevated TEWL values were measured after Dermaroller treatment compared to untreated human skin with a gradual increase of the TEWL over the first hour whereas afterwards the TEWL values decreased probably caused by a reduction of the pore size with time. Skin perforation......This study focused on the in vitro evaluation of skin perforation using a new microneedle device (Dermaroller) with different needle lengths (150, 500 and 1500 microm). The influence of the microneedle treatment on the morphology of the skin surface (studied by light and scanning electron...... microscopy), on the transepidermal water loss (TEWL) and on the penetration and permeation of hydrophilic model drugs was investigated using excised human full-thickness skin. Furthermore, invasomes - highly flexible phospholipid vesicles containing terpenes and ethanol as penetration enhancer - were...

  3. Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine.

    Directory of Open Access Journals (Sweden)

    William C Weldon

    Full Text Available Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

  4. The role of subcutaneous tissue stiffness on microneedle performance in a representative in vitro model of skin.

    Science.gov (United States)

    Moronkeji, K; Todd, S; Dawidowska, I; Barrett, S D; Akhtar, R

    2017-11-10

    There has been growing interest in the mechanical behaviour of skin due to the rapid development of microneedle devices for drug delivery applications into skin. However, most in vitro experimentation studies that are used to evaluate microneedle performance do not consider the biomechanical properties of skin or that of the subcutaneous layers. In this study, a representative experimental model of skin was developed which was comprised of subcutaneous and muscle mimics. Neonatal porcine skin from the abdominal and back regions was used, with gelatine gels of differing water content (67, 80, 88 and 96%) to represent the subcutaneous tissue, and a type of ballistic gelatine, Perma-Gel®, as a muscle mimic. Dynamic nanoindentation was used to characterize the mechanical properties of each of these layers. A custom-developed impact test rig was used to apply dense polymethylmethacrylate (PMMA) microneedles to the skin models in a controlled and repeatable way with quantification of the insertion force and velocity. Image analysis methods were used to measure penetration depth and area of the breach caused by microneedle penetration following staining and optical imaging. The nanoindentation tests demonstrated that the tissue mimics matched expected values for subcutaneous and muscle tissue, and that the compliance of the subcutaneous mimics increased linearly with water content. The abdominal skin was thinner and less stiff as compared to back skin. The maximum force decreased with gel water content in the abdominal skin but not in the back skin. Overall, larger and deeper perforations were found in the skin models with increasing water content. These data demonstrate the importance of subcutaneous tissue on microneedle performance and the need for representative skin models in microneedle technology development. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Kim, Jonghun; Park, Sungmin; Nam, Gyungmok; Choi, Young; Woo, Seungpyo; Yoon, Sang-Hee

    2018-02-01

    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 uniaxial/equibiaxial stretch of 0-20% or mechanical vibration 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. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. An Improved Manufacturing Approach for Discrete Silicon Microneedle Arrays with Tunable Height-Pitch Ratio

    Directory of Open Access Journals (Sweden)

    Renxin Wang

    2016-10-01

    Full Text Available Silicon microneedle arrays (MNAs have been widely studied due to their potential in various transdermal applications. However, discrete MNAs, as a preferred choice to fabricate flexible penetrating devices that could adapt curved and elastic tissue, are rarely reported. Furthermore, the reported discrete MNAs have disadvantages lying in uniformity and height-pitch ratio. Therefore, an improved technique is developed to manufacture discrete MNA with tunable height-pitch ratio, which involves KOH-dicing-KOH process. The detailed process is sketched and simulated to illustrate the formation of microneedles. Furthermore, the undercutting of convex mask in two KOH etching steps are mathematically analyzed, in order to reveal the relationship between etching depth and mask dimension. Subsequently, fabrication results demonstrate KOH-dicing-KOH process. {321} facet is figured out as the surface of octagonal pyramid microneedle. MNAs with diverse height and pitch are also presented to identify the versatility of this approach. At last, the metallization is realized via successive electroplating.

  7. Two-photon excited whispering-gallery mode ultraviolet laser from an individual ZnO microneedle

    Science.gov (United States)

    Zhu, G. P.; Xu, C. X.; Zhu, J.; Lv, C. G.; Cui, Y. P.

    2009-02-01

    Wurtzite structural ZnO microneedles with hexagonal cross section were fabricated by vapor-phase transport method and an individual microneedle was employed as a lasing microcavity. Under excitation of a femtosecond pulse laser with 800 nm wavelength, the ultraviolet (UV) laser emission was obtained, which presented narrow linewidth and high Q value. The UV emission, resonant mechanism, and laser mode characteristics were discussed in detail. The results demonstrated that the UV laser originated from the whispering-gallery mode induced by two-photon absorption assisted by Rabi oscillation.

  8. Assessing the Potential Cost-Effectiveness of Microneedle Patches in Childhood Measles Vaccination Programs: The Case for Further Research and Development.

    Science.gov (United States)

    Adhikari, Bishwa B; Goodson, James L; Chu, Susan Y; Rota, Paul A; Meltzer, Martin I

    2016-12-01

    Currently available measles vaccines are administered by subcutaneous injections and require reconstitution with a diluent and a cold chain, which is resource intensive and challenging to maintain. To overcome these challenges and potentially increase vaccination coverage, microneedle patches are being developed to deliver the measles vaccine. This study compares the cost-effectiveness of using microneedle patches with traditional vaccine delivery by syringe-and-needle (subcutaneous vaccination) in children's measles vaccination programs. We built a simple spreadsheet model to compute the vaccination costs for using microneedle patch and syringe-and-needle technologies. We assumed that microneedle vaccines will be, compared with current vaccines, more heat stable and require less expensive cool chains when used in the field. We used historical data on the incidence of measles among communities with low measles vaccination rates. The cost of microneedle vaccination was estimated at US$0.95 (range US$0.71-US$1.18) for the first dose, compared with US$1.65 (range US$1.24-US$2.06) for the first dose delivered by subcutaneous vaccination. At 95 % vaccination coverage, microneedle patch vaccination was estimated to cost US$1.66 per measles case averted (range US$1.24-US$2.07) compared with an estimated cost of US$2.64 per case averted (range US$1.98-US$3.30) using subcutaneous vaccination. Use of microneedle patches may reduce costs; however, the cost-effectiveness of patches would depend on the vaccine recipients' acceptability and vaccine effectiveness of the patches relative to the existing conventional vaccine-delivery method. This study emphasizes the need to continue research and development of this vaccine-delivery method that could boost measles elimination efforts through improved access to vaccines and increased vaccination coverage.

  9. Fabrication, Physicochemical Characterization, and Performance Evaluation of Biodegradable Polymeric Microneedle Patch System for Enhanced Transcutaneous Flux of High Molecular Weight Therapeutics.

    Science.gov (United States)

    Shah, Viral; Choudhury, Bijaya Krushna

    2017-11-01

    A revolutionary paradigm shift is being observed currently, towards the use of therapeutic biologics for disease management. The present research was focused on designing an efficient dosage form for transdermal delivery of α-choriogonadotropin (high molecular weight biologic), through biodegradable polymeric microneedles. Polyvinylpyrrolidone-based biodegradable microneedle arrays loaded with high molecular weight polypeptide, α-choriogonadotropin, were fabricated for its systemic delivery via transdermal route. Varied process and formulation parameters were optimized for fabricating microneedle array, which in turn was expected to temporally rupture the stratum corneum layer of the skin, acting as a major barrier to drug delivery through transdermal route. The developed polymeric microneedles were optimized on the basis of quality attributes like mechanical strength, axial strength, insertion ratio, and insertion force analysis. The optimized polymeric microneedle arrays were characterized for in vitro drug release studies, ex vivo drug permeation studies, skin resealing studies, and in vivo pharmacokinetic studies. Results depicted that fabricated polymeric microneedle arrays with mechanical strength of above 5 N and good insertion ratio exhibited similar systemic bioavailability of α-choriogonadotropin in comparison to marketed subcutaneous injection formulation of α-choriogonadotropin. Thus, it was ultimately concluded that the designed drug delivery system can serve as an efficient tool for systemic delivery of therapeutic biologics, with an added benefit of overcoming the limitations of parenteral delivery, achieving better patient acceptability and compliance.

  10. Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

    Science.gov (United States)

    Carey, John B.; Pearson, Frances E.; Vrdoljak, Anto; McGrath, Marie G.; Crean, Abina M.; Walsh, Patrick T.; Doody, Timothy; O'Mahony, Conor; Hill, Adrian V. S.; Moore, Anne C.

    2011-01-01

    Background Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8+ T cell responses to a malaria antigen induced by a live vaccine. Methodology and Findings Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. Conclusions/Significance This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8+ T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction

  11. In vivo optical coherence tomography imaging of dissolution of hyaluronic acid microneedles in human skin (Conference Presentation)

    Science.gov (United States)

    Song, Seungri; Kim, Jung Dong; Bae, Jung-hyun; Chang, Sooho; Kim, Soocheol; Lee, Hyungsuk; Jeong, Dohyeon; Kim, Hong Kee; Joo, Chulmin

    2017-02-01

    Transdermal drug delivery (TDD) has been recently highlighted as an alternative to oral delivery and hypodermic injections. Among many methods, drug delivery using a microneedle (MN) is one of the promising administration strategies due to its high skin permeability, mininal invasiveness, and ease of injection. In addition, microneedle-based TDD is explored for cosmetic and therapeutic purposes, rapidly developing market of microneedle industry for general population. To date, visualization of microneedles inserted into biological tissue has primarily been performed ex vivo. MRI, CT and ultrasound imaging do not provide sufficient spatial resolution, and optical microscopy is not suitable because of their limited imaging depth; structure of microneedles located in 0.2 1mm into the skin cannot be visulalized. Optical coherence tomography (OCT) is a non-invasive, cross-sectional optical imaging modality for biological tissue with high spatial resolution and acquisition speed. Compared with ultrasound imaging, it exhibits superior spatial resolution (1 10 um) and high sensitivity, while providing an imaging depth of biological tissue down to 1 2 mm. Here, we present in situ imaging and analysis of the penetration and dissolution characteristics of hyaluronic acid based MNs (HA-MN) with various needle heights in human skin in vivo. In contrast to other studies, we measured the actual penetration depths of the HA-MNs by considering the experimentally measured refractive index of HA in the solid state. For the dissolution dynamics of the HA-MNs, time-lapse structural alteration of the MNs could be clearly visualized, and the volumetric changes of the MNs were measured with an image analysis algorithm.

  12. Interactions among biotic and abiotic factors affect the reliability of tungsten microneedles puncturing in vitro and in vivo peripheral nerves: A hybrid computational approach

    Energy Technology Data Exchange (ETDEWEB)

    Sergi, Pier Nicola, E-mail: p.sergi@sssup.it [Translational Neural Engineering Laboratory, The Biorobotics Institute, Scuola Superiore Sant' Anna, Viale Rinaldo Piaggio 34, Pontedera, 56025 (Italy); Jensen, Winnie [Department of Health Science and Technology, Fredrik Bajers Vej 7, 9220 Aalborg (Denmark); Yoshida, Ken [Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, 723 W. Michigan St., SL220, Indianapolis, IN 46202 (United States)

    2016-02-01

    Tungsten is an elective material to produce slender and stiff microneedles able to enter soft tissues and minimize puncture wounds. In particular, tungsten microneedles are used to puncture peripheral nerves and insert neural interfaces, bridging the gap between the nervous system and robotic devices (e.g., hand prostheses). Unfortunately, microneedles fail during the puncture process and this failure is not dependent on stiffness or fracture toughness of the constituent material. In addition, the microneedles' performances decrease during in vivo trials with respect to the in vitro ones. This further effect is independent on internal biotic effects, while it seems to be related to external biotic causes. Since the exact synergy of phenomena decreasing the in vivo reliability is still not known, this work explored the connection between in vitro and in vivo behavior of tungsten microneedles through the study of interactions between biotic and abiotic factors. A hybrid computational approach, simultaneously using theoretical relationships and in silico models of nerves, was implemented to model the change of reliability varying the microneedle diameter, and to predict in vivo performances by using in vitro reliability and local differences between in vivo and in vitro mechanical response of nerves. - Highlights: • We provide phenomenological Finite Element (FE) models of peripheral nerves to study the interactions with W microneedles • We provide a general interaction-based approach to model the reliability of slender microneedles • We evaluate the reliability of W microneedels to puncture in vivo nerves • We provide a novel synergistic hybrid approach (theory + simulations) involving interactions among biotic and abiotic factors • We validate the hybrid approach by using experimental data from literature.

  13. Interactions among biotic and abiotic factors affect the reliability of tungsten microneedles puncturing in vitro and in vivo peripheral nerves: A hybrid computational approach

    International Nuclear Information System (INIS)

    Sergi, Pier Nicola; Jensen, Winnie; Yoshida, Ken

    2016-01-01

    Tungsten is an elective material to produce slender and stiff microneedles able to enter soft tissues and minimize puncture wounds. In particular, tungsten microneedles are used to puncture peripheral nerves and insert neural interfaces, bridging the gap between the nervous system and robotic devices (e.g., hand prostheses). Unfortunately, microneedles fail during the puncture process and this failure is not dependent on stiffness or fracture toughness of the constituent material. In addition, the microneedles' performances decrease during in vivo trials with respect to the in vitro ones. This further effect is independent on internal biotic effects, while it seems to be related to external biotic causes. Since the exact synergy of phenomena decreasing the in vivo reliability is still not known, this work explored the connection between in vitro and in vivo behavior of tungsten microneedles through the study of interactions between biotic and abiotic factors. A hybrid computational approach, simultaneously using theoretical relationships and in silico models of nerves, was implemented to model the change of reliability varying the microneedle diameter, and to predict in vivo performances by using in vitro reliability and local differences between in vivo and in vitro mechanical response of nerves. - Highlights: • We provide phenomenological Finite Element (FE) models of peripheral nerves to study the interactions with W microneedles • We provide a general interaction-based approach to model the reliability of slender microneedles • We evaluate the reliability of W microneedels to puncture in vivo nerves • We provide a novel synergistic hybrid approach (theory + simulations) involving interactions among biotic and abiotic factors • We validate the hybrid approach by using experimental data from literature

  14. Mechanistic studies on transcutaneous vaccine delivery : microneedles, nanoparticles and adjuvants

    NARCIS (Netherlands)

    Bal, Suzanne Marleen

    2011-01-01

    Microneedle-based transcutaneous immunisation is an appealing alternative to the classical manner of injecting vaccines by intramuscular or subcutaneous route. Importantly, as a consequence of the fact that the skin is in direct contact with the environment and should protect the body against

  15. Design, fabrication and skin-electrode contact analysis of polymer microneedle-based ECG electrodes

    Science.gov (United States)

    O'Mahony, Conor; Grygoryev, Konstantin; Ciarlone, Antonio; Giannoni, Giuseppe; Kenthao, Anan; Galvin, Paul

    2016-08-01

    Microneedle-based ‘dry’ electrodes have immense potential for use in diagnostic procedures such as electrocardiography (ECG) analysis, as they eliminate several of the drawbacks associated with the conventional ‘wet’ electrodes currently used for physiological signal recording. To be commercially successful in such a competitive market, it is essential that dry electrodes are manufacturable in high volumes and at low cost. In addition, the topographical nature of these emerging devices means that electrode performance is likely to be highly dependent on the quality of the skin-electrode contact. This paper presents a low-cost, wafer-level micromoulding technology for the fabrication of polymeric ECG electrodes that use microneedle structures to make a direct electrical contact to the body. The double-sided moulding process can be used to eliminate post-process via creation and wafer dicing steps. In addition, measurement techniques have been developed to characterize the skin-electrode contact force. We perform the first analysis of signal-to-noise ratio dependency on contact force, and show that although microneedle-based electrodes can outperform conventional gel electrodes, the quality of ECG recordings is significantly dependent on temporal and mechanical aspects of the skin-electrode interface.

  16. Design, fabrication and skin-electrode contact analysis of polymer microneedle-based ECG electrodes

    International Nuclear Information System (INIS)

    O’Mahony, Conor; Grygoryev, Konstantin; Ciarlone, Antonio; Giannoni, Giuseppe; Kenthao, Anan; Galvin, Paul

    2016-01-01

    Microneedle-based ‘dry’ electrodes have immense potential for use in diagnostic procedures such as electrocardiography (ECG) analysis, as they eliminate several of the drawbacks associated with the conventional ‘wet’ electrodes currently used for physiological signal recording. To be commercially successful in such a competitive market, it is essential that dry electrodes are manufacturable in high volumes and at low cost. In addition, the topographical nature of these emerging devices means that electrode performance is likely to be highly dependent on the quality of the skin-electrode contact.This paper presents a low-cost, wafer-level micromoulding technology for the fabrication of polymeric ECG electrodes that use microneedle structures to make a direct electrical contact to the body. The double-sided moulding process can be used to eliminate post-process via creation and wafer dicing steps. In addition, measurement techniques have been developed to characterize the skin-electrode contact force. We perform the first analysis of signal-to-noise ratio dependency on contact force, and show that although microneedle-based electrodes can outperform conventional gel electrodes, the quality of ECG recordings is significantly dependent on temporal and mechanical aspects of the skin-electrode interface. (paper)

  17. Optimization of naltrexone diclofenac codrugs for sustained drug delivery across microneedle-treated skin.

    Science.gov (United States)

    Ghosh, Priyanka; Lee, DoMin; Kim, Kyung Bo; Stinchcomb, Audra L

    2014-01-01

    The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetime following microneedle treatment and develop a 7 day transdermal system for naltrexone. Four different codrugs of naltrexone and diclofenac were compared in terms of stability and solubility. Transdermal flux, permeability and skin concentration of both parent drugs and codrugs were quantified to form a structure permeability relationship. The results indicated that all codrugs bioconverted in the skin. The degree of conversion was dependent on the structure, phenol linked codrugs were less stable compared to the secondary alcohol linked structures. The flux of naltrexone across microneedle treated skin and the skin concentration of diclofenac were higher for the phenol linked codrugs. The polyethylene glycol link enhanced solubility of the codrugs, which translated into flux enhancement. The current studies indicated that formulation stability of codrugs and the flux of naltrexone can be enhanced via structure design optimization. The polyethylene glycol linked naltrexone diclofenac codrug is better suited for a 7 day drug delivery system both in terms of stability and drug delivery.

  18. MoS2/Pt nanocomposite-functionalized microneedle for real-time monitoring of hydrogen peroxide release from living cells.

    Science.gov (United States)

    Zhou, Jin-Xiu; Tang, Li-Na; Yang, Fan; Liang, Feng-Xia; Wang, Hua; Li, Yu-Tao; Zhang, Guo-Jun

    2017-11-06

    This work describes the adaptive use of a conventional stainless steel acupuncture needle as the electrode substrate for construction of a molybdenum disulfide (MoS 2 ) and platinum nanoparticles (PtNPs) layer-modified microneedle sensor for real-time monitoring of hydrogen peroxide (H 2 O 2 ) release from living cells. To construct the nanocomposite-functionalized microneedle, the needle surface was first coated with a gold film by ion sputtering to enhance the conductivity. Subsequently, an electrochemical deposition method was successfully employed to deposit MoS 2 nanosheet and Pt nanoparticles on the needle tip as the sensing interface. Electrochemical study demonstrated that the MoS 2 /PtNPs nanocomposite-modified needle exhibited excellent catalytic performance and low over-potential toward the reduction of H 2 O 2 . Not only did the microneedle achieve a wide linear range from 1 to 100 μmol L -1 with a limit of detection down to 0.686 μmol L -1 , but it also realized the highly specific detection of H 2 O 2 . Owing to these remarkable analytical advantages, the prepared microneedle was applied to determine H 2 O 2 release from living cells with satisfactory results. The MoS 2 /PtNPs nanocomposite-functionalized microneedle sensor is simple and affordable, and can serve as a promising electrochemical nonenzymatic sensing platform. Moreover, this superfine needle sensor shows great potential for real-time monitoring of reactive oxygen species in vivo with minimal damage.

  19. Fabrication of a Micro-Needle Array Electrode by Thermal Drawing for Bio-Signals Monitoring.

    Science.gov (United States)

    Ren, Lei; Jiang, Qing; Chen, Keyun; Chen, Zhipeng; Pan, Chengfeng; Jiang, Lelun

    2016-06-17

    A novel micro-needle array electrode (MAE) fabricated by thermal drawing and coated with Ti/Au film was proposed for bio-signals monitoring. A simple and effective setup was employed to form glassy-state poly (lactic-co-glycolic acid) (PLGA) into a micro-needle array (MA) by the thermal drawing method. The MA was composed of 6 × 6 micro-needles with an average height of about 500 μm. Electrode-skin interface impedance (EII) was recorded as the insertion force was applied on the MAE. The insertion process of the MAE was also simulated by the finite element method. Results showed that MAE could insert into skin with a relatively low compression force and maintain stable contact impedance between the MAE and skin. Bio-signals, including electromyography (EMG), electrocardiography (ECG), and electroencephalograph (EEG) were also collected. Test results showed that the MAE could record EMG, ECG, and EEG signals with good fidelity in shape and amplitude in comparison with the commercial Ag/AgCl electrodes, which proves that MAE is an alternative electrode for bio-signals monitoring.

  20. Fabrication of a Micro-Needle Array Electrode by Thermal Drawing for Bio-Signals Monitoring

    Directory of Open Access Journals (Sweden)

    Lei Ren

    2016-06-01

    Full Text Available A novel micro-needle array electrode (MAE fabricated by thermal drawing and coated with Ti/Au film was proposed for bio-signals monitoring. A simple and effective setup was employed to form glassy-state poly (lactic-co-glycolic acid (PLGA into a micro-needle array (MA by the thermal drawing method. The MA was composed of 6 × 6 micro-needles with an average height of about 500 μm. Electrode-skin interface impedance (EII was recorded as the insertion force was applied on the MAE. The insertion process of the MAE was also simulated by the finite element method. Results showed that MAE could insert into skin with a relatively low compression force and maintain stable contact impedance between the MAE and skin. Bio-signals, including electromyography (EMG, electrocardiography (ECG, and electroencephalograph (EEG were also collected. Test results showed that the MAE could record EMG, ECG, and EEG signals with good fidelity in shape and amplitude in comparison with the commercial Ag/AgCl electrodes, which proves that MAE is an alternative electrode for bio-signals monitoring.

  1. Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin

    NARCIS (Netherlands)

    Verbaan, F.J.; Bal, S.M.; van den Berg, D.J.; Groenink, W.H.H.; Verpoorten, H.; Lüttge, Regina; Bouwstra, J.A.

    2007-01-01

    In this study, we demonstrate the feasibility to use microneedle arrays manufactured from commercially available 30G hypodermal needles to enhance the transport of compounds up to a molecular weight of 72 kDa. Piercing of human dermatomed skin with microneedle arrays was studied by Trypan Blue

  2. Effect of zymosan and poly (I:C) adjuvants on responses to microneedle immunization coated with whole inactivated influenza vaccine.

    Science.gov (United States)

    Shin, Ju-Hyung; Noh, Jin-Yong; Kim, Kwon-Ho; Park, Jae-Keun; Lee, Ji-Ho; Jeong, Seong Dong; Jung, Dae-Yoon; Song, Chang-Seon; Kim, Yeu-Chun

    2017-11-10

    Microneedles are the micrometer size devices used for the delivery of vaccines and biotherapeutics. In order to increase the vaccine efficacy and reduce the antigen dose, there is a significant need to find some adjuvants for the microneedle vaccination. In this study, zymosan, which is the cell wall preparation of Saccharomyces cerevisiae, or poly (I:C) was coated on a microneedle with inactivated influenza virus, and then immunized into BALB/c mouse to determine the immunogenicity, protection and synergetic effect between two adjuvants. As a result, the group administered with zymosan and vaccine antigen showed significantly stronger IgG response, HI titer and IgG subtypes without any adverse effects, compared to the group immunized with the vaccine antigen alone. Also, there were enhanced cellular immune responses in the group received adjuvant with vaccine antigen. In addition, they showed superior protection and lung viral reduction against lethal viral challenge. Taken together, this study confirms that zymosan can be used as an immunostimulant for microneedle vaccination. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A Biodegradable Microneedle Cuff for Comparison of Drug Effects through Perivascular Delivery to Balloon-Injured Arteries

    Directory of Open Access Journals (Sweden)

    Dae-Hyun Kim

    2017-02-01

    Full Text Available Restenosis at a vascular anastomosis site is a major cause of graft failure and is difficult to prevent by conventional treatment. Perivascular drug delivery has advantages as drugs can be diffused to tunica media and subintima while minimizing the direct effect on endothelium. This in vivo study investigated the comparative effectiveness of paclitaxel, sirolimus, and sunitinib using a perivascular biodegradable microneedle cuff. A total of 31 New Zealand white rabbits were used. Rhodamine was used to visualize drug distribution (n = 3. Sirolimus- (n = 7, sunitinib- (n = 7, and paclitaxel-loaded (n = 7 microneedle cuffs were placed at balloon-injured abdominal aortae and compared to drug-free cuffs (n = 7. Basic histological structures were not affected by microneedle devices, and vascular wall thickness of the device-only group was similar to that of normal artery. Quantitative analysis revealed significantly decreased neointima formation in all drug-treated groups (p < 0.001. However, the tunica media layer of the paclitaxel-treated group was significantly thinner than that of other groups and also showed the highest apoptotic ratio (p < 0.001. Proliferating cell nuclear antigen (PCNA-positive cells were significantly reduced in all drug-treated groups. Sirolimus or sunitinib appeared to be more appropriate for microneedle devices capable of slow drug release because vascular wall thickness was minimally affected.

  4. Review of recent literature on microneedle vaccine delivery technologies

    Directory of Open Access Journals (Sweden)

    Vrdoljak A

    2013-08-01

    Full Text Available Anto Vrdoljak Development Laboratory, Genera, Rakov Potok, Croatia Abstract: Microneedles (MNs have been developed as medical devices for enhanced and painless transdermal drug and vaccine delivery. MN-based vaccine application, unlike conventional intramuscular or subcutaneous application using hypodermic needles, delivers vaccine directly into skin, which is known to be an immunologically much more relevant vaccination site than underlying tissue. Vaccination using MN devices targets the skin's rich immune system, leading to better utilization of the antigen and resulting in superior immune response, often achieved using a lower vaccine dose than required by conventional delivery routes. However, despite the number of advantages and nearly four decades of research, the number of licensed MN-based vaccines remains limited to date. Nevertheless, it is to be expected that on the back of a number of recently developed scalable and robust MN-fabrication methods, more intensive translation into clinical practice will follow. Here, we review the current status and trends in research of MN-related vaccine delivery platforms, focusing on the most promising approaches and clinically relevant applications. Keywords: microneedles, vaccine delivery, skin vaccination

  5. Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery.

    Science.gov (United States)

    Wang, Jinqiang; Ye, Yanqi; Yu, Jicheng; Kahkoska, Anna R; Zhang, Xudong; Wang, Chao; Sun, Wujin; Corder, Ria D; Chen, Zhaowei; Khan, Saad A; Buse, John B; Gu, Zhen

    2018-03-27

    A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H 2 O 2 ) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H 2 O 2 -responsive microneedles are coated with a thin-layer embedding H 2 O 2 -scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and protective shell could effectively regulate the blood glucose levels within a normal range with improved biocompatibility.

  6. Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin.

    Science.gov (United States)

    Liu, Shu; Jin, Mei-na; Quan, Ying-shu; Kamiyama, Fumio; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2014-02-01

    The purpose of this study was to develop novel dissolving microneedle arrays fabricated from hyaluronic acid (HA) as a material and to improve the transdermal permeability of relatively high molecular weight drugs. In this study, fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4kDa (FD4) was used as a model drug with a relatively high molecular weight. The microneedle arrays significantly increased transepidermal water loss (TEWL) and reduced transcutaneous electrical resistance (TER), indicating that they could puncture the skin and create drug permeation pathways successfully. Both TEWL and TER almost recovered to baseline levels in the microneedle array group, and relatively small pathways created by the microneedles rapidly recovered as compared with those created by a tape stripping treatment. These findings confirmed that the microneedle arrays were quite safe. Furthermore, we found that the transdermal permeability of FD4 using the microneedle arrays was much higher than that of the FD4 solution. Furthermore, we found that the microneedle arrays were much more effective for increasing the amount of FD4 accumulated in the skin. These findings indicated that using novel microneedle arrays fabricated from HA is a very useful and effective strategy to improve the transdermal delivery of drugs, especially relatively high molecular weight drugs without seriously damaging the skin. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Microneedling dilates the follicular infundibulum and increases transfollicular absorption of liposomal sepia melanin

    Directory of Open Access Journals (Sweden)

    Serrano G

    2015-06-01

    Full Text Available Gabriel Serrano,1 Patricia Almudéver,2 Juan M Serrano,3 Julio Cortijo,2 Carmen Faus,1 Magda Reyes,1 Inmaculada Expósito,3 Ana Torrens,3 Fernando Millán1 1Clínica Dermatológica Serrano, 2Department of Pharmacology, University of Valencia, 3Research and Development Department, Sesderma Laboratories, Valencia, Spain Abstract: Encapsulation of chemicals in liposomes and microneedling are currently used techniques to enhance the penetration of several substances through skin and hair. In this study, we apply a liposomal melanin–fluorescein compound to an ex vivo model of human skin, using a new electrical microneedling device (Nanopore turbo roller. The product was applied by hand massage (A or with the assistance of the electrical roller for 2 minutes (B. An additional test was performed free of product and with only the E-roller (C. Histological changes and product absorption were evaluated by optical and fluorescent microscopy 60 and 90 minutes after the treatment. Site B showed larger deposits of melanin–fluorescein at superficial and deep levels of hair structures in comparison to site A. Light, epidermal deposits of the melanin–fluorescein complex were also observed. Sites B and C showed a significant widening (47% of the follicular infundibulum which could explain the increased penetration of the formulation. Microneedling also removed the scales and sebum residues in the neighborhood of the infundibulum. Targeting hair follicles with melanin may be useful to dye poorly pigmented hairs, improving laser hair removal. The procedure accelerates the delivery of melanin into hair structures allowing an even absorption, larger pigment deposits, and deeper penetration of the formulation into the hair. Keywords: liposomes, melanin, microneedling, follicular infundibulum, hair removal

  8. Revolutionizing Therapeutic Drug Monitoring with the Use of Interstitial Fluid and Microneedles Technology

    Science.gov (United States)

    Kiang, Tony K.L.; Ranamukhaarachchi, Sahan A.; Ensom, Mary H.H.

    2017-01-01

    While therapeutic drug monitoring (TDM) that uses blood as the biological matrix is the traditional gold standard, this practice may be impossible, impractical, or unethical for some patient populations (e.g., elderly, pediatric, anemic) and those with fragile veins. In the context of finding an alternative biological matrix for TDM, this manuscript will provide a qualitative review on: (1) the principles of TDM; (2) alternative matrices for TDM; (3) current evidence supporting the use of interstitial fluid (ISF) for TDM in clinical models; (4) the use of microneedle technologies, which is potentially minimally invasive and pain-free, for the collection of ISF; and (5) future directions. The current state of knowledge on the use of ISF for TDM in humans is still limited. A thorough literature review indicates that only a few drug classes have been investigated (i.e., anti-infectives, anticonvulsants, and miscellaneous other agents). Studies have successfully demonstrated techniques for ISF extraction from the skin but have failed to demonstrate commercial feasibility of ISF extraction followed by analysis of its content outside the ISF-collecting microneedle device. In contrast, microneedle-integrated biosensors built to extract ISF and perform the biomolecule analysis on-device, with a key feature of not needing to transfer ISF to a separate instrument, have yielded promising results that need to be validated in pre-clinical and clinical studies. The most promising applications for microneedle-integrated biosensors is continuous monitoring of biomolecules from the skin’s ISF. Conducting TDM using ISF is at the stage where its clinical utility should be investigated. Based on the advancements described in the current review, the immediate future direction for this area of research is to establish the suitability of using ISF for TDM in human models for drugs that have been found suitable in pre-clinical experiments. PMID:29019915

  9. Revolutionizing Therapeutic Drug Monitoring with the Use of Interstitial Fluid and Microneedles Technology

    Directory of Open Access Journals (Sweden)

    Tony K.L. Kiang

    2017-10-01

    Full Text Available While therapeutic drug monitoring (TDM that uses blood as the biological matrix is the traditional gold standard, this practice may be impossible, impractical, or unethical for some patient populations (e.g., elderly, pediatric, anemic and those with fragile veins. In the context of finding an alternative biological matrix for TDM, this manuscript will provide a qualitative review on: (1 the principles of TDM; (2 alternative matrices for TDM; (3 current evidence supporting the use of interstitial fluid (ISF for TDM in clinical models; (4 the use of microneedle technologies, which is potentially minimally invasive and pain-free, for the collection of ISF; and (5 future directions. The current state of knowledge on the use of ISF for TDM in humans is still limited. A thorough literature review indicates that only a few drug classes have been investigated (i.e., anti-infectives, anticonvulsants, and miscellaneous other agents. Studies have successfully demonstrated techniques for ISF extraction from the skin but have failed to demonstrate commercial feasibility of ISF extraction followed by analysis of its content outside the ISF-collecting microneedle device. In contrast, microneedle-integrated biosensors built to extract ISF and perform the biomolecule analysis on-device, with a key feature of not needing to transfer ISF to a separate instrument, have yielded promising results that need to be validated in pre-clinical and clinical studies. The most promising applications for microneedle-integrated biosensors is continuous monitoring of biomolecules from the skin’s ISF. Conducting TDM using ISF is at the stage where its clinical utility should be investigated. Based on the advancements described in the current review, the immediate future direction for this area of research is to establish the suitability of using ISF for TDM in human models for drugs that have been found suitable in pre-clinical experiments.

  10. ASSESSMENT OF MICRONEEDLING THERAPY IN THE MANAGEMENT OF ATROPHIC FACIAL ACNE SCARS

    Directory of Open Access Journals (Sweden)

    Ajay

    2015-12-01

    Full Text Available STUDY BACKGROUND Post acne scars are always a challenge to treat, especially the ones which are deep seated. There are many treatment options like laser resurfacing, dermabrasion, microdermabrasion and non-ablative laser resurfacing but with considerable morbidity and interference with the daily activities of the patient in the post-treatment period. Microneedling or dermaroller therapy is one of the new treatment options in the management of acne scars with satisfactory improvement and no significant side effect. The aim of the present study is to perform an objective evaluation the efficacy of microneedling in the treatment of atrophic acne scars. MATERIALS AND METHODS Thirty patients of skin type III-V having atrophic facial acne scars presenting to our dermatology OPD. were received multiple sittings of microneedling (dermaroller treatment with an interval of 6 weeks between each session. Goodman & Baron’s acne scar grading system was used for assessment of their scars and was evaluated clinically by serial photography at the start as well as at two months after the conclusion of the treatment. Patients on anticoagulant therapy, of keloidal tendency, with bleeding disorders, vitiligo patients, pregnant and lactating mothers and patients with active acne lesions were excluded from the study. The duration of this study was for ten months-from January 2014 to October 2014. RESULTS Any change in the grading of scars after the end of treatment and follow-up period was noted down. The efficacy and improvement of dermaroller treatment was assessed by Goodman and Baron’s Global Acne Scarring System. Out of 30 patients, 26(80.64% patients achieved a reduction in the severity of their scarring by one or two grades. Quantitative assessment showed that 13.3% of patients had minimal, 16.6% had good and 70% showed very good improvement. Adverse effects were limited to transient pain, erythema and edema. CONCLUSION Microneedling therapy seems to be

  11. Microneedle pH Sensor: Direct, Label-Free, Real-Time Detection of Cerebrospinal Fluid and Bladder pH.

    Science.gov (United States)

    Mani, Ganesh Kumar; Miyakoda, Kousei; Saito, Asuka; Yasoda, Yutaka; Kajiwara, Kagemasa; Kimura, Minoru; Tsuchiya, Kazuyoshi

    2017-07-05

    Acid-base homeostasis (body pH) inside the body is precisely controlled by the kidneys and lungs and buffer systems, such that even a minor pH change could severely affect many organs. Blood and urine pH tests are common in day-to-day clinical trials and require little effort for diagnosis. There is always a great demand for in vivo testing to understand more about body metabolism and to provide effective diagnosis and therapy. In this article, we report the simple fabrication of microneedle-based direct, label-free, and real-time pH sensors. The reference and working electrodes were Ag/AgCl thick films and ZnO thin films on tungsten (W) microneedles, respectively. The morphological and structural characteristics of microneedles were carefully investigated through various analytical methods. The developed sensor exhibited a Nernstian response of -46 mV/pH. Different conditions were used to test the sensor to confirm their accuracy and stability, such as various buffer solutions, with respect to time, and we compared the reading with commercial pH electrodes. Besides that, the fabricated microneedle sensor ability is proven by in vivo testing in mouse cerebrospinal fluid (CSF) and bladders. The pH sensor procedure reported here is totally reversible, and results were reproducible after several rounds of testing.

  12. The Use of a Pressure-Indicating Sensor Film to Provide Feedback upon Hydrogel-Forming Microneedle Array Self-Application In Vivo.

    Science.gov (United States)

    Vicente-Pérez, Eva M; Quinn, Helen L; McAlister, Emma; O'Neill, Shannon; Hanna, Lezley-Anne; Barry, Johanne G; Donnelly, Ryan F

    2016-12-01

    To evaluate the combination of a pressure-indicating sensor film with hydrogel-forming microneedle arrays, as a method of feedback to confirm MN insertion in vivo. Pilot in vitro insertion studies were conducted using a Texture Analyser to insert MN arrays, coupled with a pressure-indicating sensor film, at varying forces into excised neonatal porcine skin. In vivo studies involved twenty human volunteers, who self-applied two hydrogel-forming MN arrays, one with a pressure-indicating sensor film incorporated and one without. Optical coherence tomography was employed to measure the resulting penetration depth and colorimetric analysis to investigate the associated colour change of the pressure-indicating sensor film. Microneedle insertion was achieved in vitro at three different forces, demonstrating the colour change of the pressure-indicating sensor film upon application of increasing pressure. When self-applied in vivo, there was no significant difference in the microneedle penetration depth resulting from each type of array, with a mean depth of 237 μm recorded. When the pressure-indicating sensor film was present, a colour change occurred upon each application, providing evidence of insertion. For the first time, this study shows how the incorporation of a simple, low-cost pressure-indicating sensor film can indicate microneedle insertion in vitro and in vivo, providing visual feedback to assure the user of correct application. Such a strategy may enhance usability of a microneedle device and, hence, assist in the future translation of the technology to widespread clinical use.

  13. Successful transdermal allergen delivery and allergen-specific immunotherapy using biodegradable microneedle patches.

    Science.gov (United States)

    Kim, Ji Hye; Shin, Jung U; Kim, Seo Hyeong; Noh, Ji Yeon; Kim, Hye Ran; Lee, Jungsoo; Chu, Howard; Jeong, Kyoung Yong; Park, Kyung Hee; Kim, Jung Dong; Kim, Hong Kee; Jeong, Do Hyeon; Yong, Tai-Soon; Park, Jung-Won; Lee, Kwang Hoon

    2018-01-01

    Allergen-specific immunotherapy (SIT) is an effective treatment modality for allergic diseases such as atopic dermatitis (AD). However, frequent visits over a 3-year period as well as looming adverse events tend to discourage patient compliance. Therefore, a more convenient, effective, and safe method of SIT is needed. For several decades, use of microneedles has been promoted as an efficient and precise transdermal drug delivery method. In this study, we developed Dermatophagoides farinae (D. farinae) extract (DfE)-loaded microneedle patches, and evaluated their safety and efficacy as a novel SIT method. After 4 weeks of patch application, efficient allergen delivery and successful induction of immune response to DfE were demonstrated in mice, with no apparent adverse events. AD-induced NC/Nga mice received microneedle immunotherapy (MNIT) (10 μg), subcutaneous immunotherapy (SCIT) (10 μg), SCIT (100 μg), or placebo. Both MNIT (10 μg) and SCIT (100 μg) treatments improved clinical and histologic manifestations of AD skin lesions, altered immunoglobulin production, dampened Th2 cellular response, and boosted Treg infiltrates, without significant side effects; whereas SCIT (10 μg) or placebo subsets failed to show any effects. Based on the favorable safety and efficacy profiles demonstrated in mice by MNIT in the current study, we believe that MNIT may serve as a new SIT modality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Fabrication of Polymer Microneedle Electrodes Coated with Nanoporous Parylene

    Science.gov (United States)

    Nishinaka, Yuya; Jun, Rina; Setia Prihandana, Gunawan; Miki, Norihisa

    2013-06-01

    In this study, we demonstrate the fabrication of polymer microneedle electrodes covered with a nanoporous parylene film that can serve as flexible electrodes for a brain-machine interface. In brain wave measurement, the electric impedance of electrodes should be below 10 kΩ at 15 Hz, and the conductive layer needs to be protected to survive its insertion into the stratum corneum. Polymer microneedles can be used as substrates for flexible electrodes, which can compensate for the movement of the skin; however, the adhesion between a conductive metal film, such as a silver film, and a polymer, such as poly(dimethylsiloxane) (PDMS), is weak. Therefore, we coated the electrode surface with a nanoporous parylene film, following the vapor deposition of a silver film. When the porosity of the parylene film is appropriate, it protects the silver film while allowing the electrode to have sufficient conductivity. The porosity can be controlled by adjusting the amount of the parylene dimer used for the deposition or the parylene film thickness. We experimentally verified that a conductive membrane was successfully protected while maintaining a conductivity below 10 kΩ when the thickness of the parylene film was between 25 and 38 nm.

  15. Ag coated microneedle based surface enhanced Raman scattering probe for intradermal measurements

    Science.gov (United States)

    Yuen, Clement; Liu, Quan

    2013-06-01

    We propose a silver coated microneedle to detect test molecules, including R6G and glucose, positioned at a depth of more than 700 μm below a skin phantom surface for mimicking intradermal surface-enhanced Raman scattering measurements.

  16. Fabrication of Flexible Microneedle Array Electrodes for Wearable Bio-Signal Recording.

    Science.gov (United States)

    Ren, Lei; Xu, Shujia; Gao, Jie; Lin, Zi; Chen, Zhipeng; Liu, Bin; Liang, Liang; Jiang, Lelun

    2018-04-13

    Laser-direct writing (LDW) and magneto-rheological drawing lithography (MRDL) have been proposed for the fabrication of a flexible microneedle array electrode (MAE) for wearable bio-signal monitoring. Conductive patterns were directly written onto the flexible polyethylene terephthalate (PET) substrate by LDW. The microneedle array was rapidly drawn and formed from the droplets of curable magnetorheological fluid with the assistance of an external magnetic field by MRDL. A flexible MAE can maintain a stable contact interface with curved human skin due to the flexibility of the PET substrate. Compared with Ag/AgCl electrodes and flexible dry electrodes (FDE), the electrode-skin interface impedance of flexible MAE was the minimum even after a 50-cycle bending test. Flexible MAE can record electromyography (EMG), electroencephalography (EEG) and static electrocardiography (ECG) signals with good fidelity. The main features of the dynamic ECG signal recorded by flexible MAE are the most distinguishable with the least moving artifacts. Flexible MAE is an attractive candidate electrode for wearable bio-signal monitoring.

  17. Microneedle arrays for biosensing and drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger; Miller, Philip

    2017-08-29

    Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

  18. Microneedle arrays for biosensing and drug delivery

    Science.gov (United States)

    Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger; Miller, Philip; Polsky, Ronen; Edwards, Thayne L.

    2017-08-22

    Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a^ device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

  19. Hollow-in-Hollow Carbon Spheres for Lithium-ion Batteries with Superior Capacity and Cyclic Performance

    International Nuclear Information System (INIS)

    Zang, Jun; Ye, Jianchuan; Fang, Xiaoliang; Zhang, Xiangwu; Zheng, Mingsen; Dong, Quanfeng

    2015-01-01

    Highlights: • Hollow-in-hollow structured HIHCS was synthesized via a facile templating strategy. • The HCS core and hollow carbon shell constitute the hollow-in-hollow structure. • The HIHCS exhibited superior rate capability and cycle stability as anode material. • The excellent performance is attributed to the unique hollow-in-hollow structure. - Abstract: Hollow spheres structured materials have been intensively pursued due to their unique properties for energy storage. In this paper, hollow-in-hollow carbon spheres (HIHCS) with a multi-shelled structure were successfully synthesized using a facile hard-templating procedure. When evaluated as anode material for lithium-ion batteries, the resultant HIHCS anode exhibited superior capacity and cycling stability than HCS. It could deliver reversible capacities of 937, 481, 401, 304 and 236 mAh g −1 at current densities of 0.1 A g −1 , 1 A g −1 , 2 A g −1 , 5 A g −1 and 10 A g −1 , respectively. And capacity fading is not apparent in 500 cycles at 5 A g −1 . The excellent performance of the HIHCS anode is ascribed to its unique hollow-in-hollow structure and high specific surface area.

  20. An evaluation of the antiaging properties of strawberry hydrolysate treatment enriched with L-ascorbic acid applied with microneedle mesotherapy.

    Science.gov (United States)

    Markiewicz, Agata; Zasada, Malwina; Erkiert-Polguj, Anna; Wieckowska-Szakiel, Marzena; Budzisz, Elzbieta

    2018-04-16

    Mature skin is characterized by a loss of elasticity, hyperpigmentation, and dehydration. L-ascorbic acid stimulates the synthesis of collagen type I, inhibits melanogenesis, and helps to maintain correct skin hydration. Combining microneedle mesotherapy with the application of preparations rich in vitamin C results in better therapeutic effects due to the improved absorption of active substances. The study evaluates the effectiveness of the application of strawberry hydrolysate enriched with L-ascorbic acid using microneedle mesotherapy. Seventeen volunteers aged 45-70 years underwent a series of four microneedle mesotherapy treatments with vitamin C serum, performed every 10 days. The 20% L-ascorbic acid solution (pH = 3.5) was prepared immediately before application. After the treatment, the participants gave a subjective assessment of the effectiveness. Cutometer ® was used to measure skin elasticity and firmness, Corneometer ® to measure skin hydration, and Mexameter ® skin tone. The results of the survey showed improvements in skin hydration and elasticity. In vivo studies confirmed the effectiveness of serum and the impact of the active substance on skin firmness and elasticity, the degree of hydration and skin tone. Microneedling with vitamin C improves skin tone, hydratation and firmness, and decreases the visibility of hyperpigmentation. © 2018 Wiley Periodicals, Inc.

  1. A minimally invasive micro sampler for quantitative sampling with an ultrahigh-aspect-ratio microneedle and a PDMS actuator.

    Science.gov (United States)

    Liu, Long; Wang, Yan; Yao, Jinyuan; Yang, Cuijun; Ding, Guifu

    2016-08-01

    This study describes a novel micro sampler consisting of an ultrahigh-aspect-ratio microneedle and a PDMS actuator. The microneedle was fabricated by a new method which introduced reshaped photoresist technology to form a flow channel inside. The microneedle includes two parts: shaft and pedestal. In this study, the shaft length is 1500 μm with a 45° taper angle on the tip and pedestal is 1000 μm. Besides, the shaft and pedestal are connected by an arc connection structure with a length of 600 μm. The microneedles have sufficient mechanical strength to insert into skin with a wide safety margin which was proved by mechanics tests. Moreover, a PDMS actuator with a chamber inside was designed and fabricated in this study. The chamber, acting as a reservoir in sampling process as well as providing power, was optimized by finite element analysis (FEA) to decrease dead volume and improve sampling precision. The micro sampler just needs finger press to activate the sampling process as well as used for quantitative micro injection to some extent. And a volume of 31.5 ± 0.8 μl blood was successfully sampled from the ear artery of a rabbit. This micro sampler is suitable for micro sampling for diagnose or therapy in biomedical field.

  2. Induction of CD8(+) T cell responses and protective efficacy following microneedle-mediated delivery of a live adenovirus-vectored malaria vaccine.

    Science.gov (United States)

    Pearson, Frances E; O'Mahony, Conor; Moore, Anne C; Hill, Adrian V S

    2015-06-22

    There is an urgent need for improvements in vaccine delivery technologies. This is particularly pertinent for vaccination programmes within regions of limited resources, such as those required for adequate provision for disposal of used needles. Microneedles are micron-sized structures that penetrate the stratum corneum of the skin, creating temporary conduits for the needle-free delivery of drugs or vaccines. Here, we aimed to investigate immunity induced by the recombinant simian adenovirus-vectored vaccine ChAd63.ME-TRAP; currently undergoing clinical assessment as a candidate malaria vaccine, when delivered percutaneously by silicon microneedle arrays. In mice, we demonstrate that microneedle-mediated delivery of ChAd63.ME-TRAP induced similar numbers of transgene-specific CD8(+) T cells compared to intradermal (ID) administration with needle-and-syringe, following a single immunisation and after a ChAd63/MVA heterologous prime-boost schedule. When mice immunised with ChAd63/MVA were challenged with live Plasmodium berghei sporozoites, microneedle-mediated ChAd63.ME-TRAP priming demonstrated equivalent protective efficacy as did ID immunisation. Furthermore, responses following ChAd63/MVA immunisation correlated with a specific design parameter of the array used ('total array volume'). The level of transgene expression at the immunisation site and skin-draining lymph node (dLN) was also linked to total array volume. These findings have implications for defining silicon microneedle array design for use with live, vectored vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Dissolving polyvinylpyrrolidone-based microneedle systems for in-vitro delivery of sumatriptan succinate.

    Science.gov (United States)

    Ronnander, P; Simon, L; Spilgies, H; Koch, A; Scherr, S

    2018-03-01

    In-vitro permeation studies were conducted to assess the feasibility of fabricating dissolving-microneedle-array systems to release sumatriptan succinate. The formulations consisted mainly of the encapsulated active ingredient and a water-soluble biologically compatible polymer, polyvinylpyrrolidone (PVP), approved by the U.S. Food and Drug Administration (FDA). Tests with Franz-type diffusion cells and Göttingen minipig skins showed an increase of the transdermal flux compared to passive diffusion. A preparation, containing 30% by mass of PVP and 8.7mg sumatriptan, produced a delivery rate of 395±31μg/cm 2 h over a 7-hour period after a negligible lag time of approximately 39min. Theoretically, a 10.7cm 2 microneedle-array patch loaded with 118.8mg of the drug would provide the required plasma concentration, 72ng/mL, for nearly 7h. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Nonenzymatic determination of glucose at near neutral pH values based on the use of nafion and platinum black coated microneedle electrode array.

    Science.gov (United States)

    Chinnadayyala, Somasekhar R; Park, Ilhwan; Cho, Sungbo

    2018-04-07

    The authors report on a microneedle-based amperometric nonenzymatic glucose sensor for painless and continuous monitoring of glucose. It consists of 3 × 5 sharp stainless steel microneedles micromachined from a stainless steel substrate. The microneedles are 600 and 100 μm in height and width, respectively. Nafion and platinum black were sequentially coated onto the tip of gold-coated microneedles and used for nonenzymatic (direct) sensing of glucose. Attractive features of the modified microneedle electrode include (a) a low working potential (+0.12 V vs. Ag/AgCl), (b) a linear response in the physiologically relevant range (1-40 mM), (c) a sensitivity as high as 175 μA mM -1  cm -2 , (d) a 23 μM detection limit, and (e) a response time of 2 s. The sensor also exhibits good reproducibility and stability. The sensor is selective for glucose even in the presence of 10-fold higher concentrations of ascorbic acid, lactic acid, dopamine, uric acid, and acetaminophen. Graphical abstract Schematic representation of the fabrication sequence for a nonenzymatic electrochemical glucose sensor using Nafion and platinum black coated microneedle electrode array. The sensor is based on measuring the faradaic current at +0.12 V vs. Ag/AgCl by the direct electrochemical oxidation of glucose to gluconic acid on the surface of a Pt black sensing layer.

  5. Insertion Testing of Polyethylene Glycol Microneedle Array into Cultured Human Skin with Biaxial Tension

    Science.gov (United States)

    Takano, Naoki; Tachikawa, Hiroto; Miyano, Takaya; Nishiyabu, Kazuaki

    Aiming at the practical use of polyethylene glycol (PEG) microneedles for transdermal drug delivery system (DDS), a testing apparatus for their insertion into cultured human skin has been developed. To simulate the variety of conditions of human skin, biaxial tension can be applied to the cultured human skin. An adopted testing scheme to apply and control the biaxial tension is similar to the deep-draw forming technique. An attention was also paid to the short-time setup of small, thin and wet cultured skin. One dimensional array with four needles was inserted and influence of tension was discussed. It was found that tension, deflection of skin during insertion and original curvature of skin are the important parameters for microneedles array design.

  6. Switching a Nanocluster Core from Hollow to Non-hollow

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa

    2016-03-24

    Modulating the structure-property relationship in atomically precise nanoclusters (NCs) is vital for developing novel NC materials and advancing their applications. While promising biphasic ligand-exchange (LE) strategies have been developed primarily to attain novel NCs, understanding the mechanistic aspects involved in tuning the core and the ligand-shell of NCs in such biphasic processes is challenging. Here, we design a single phase LE process that enabled us to elucidate the mechanism of how a hollow NC (e.g., [Ag44(SR)30]4-, -SR: thiolate) converts into a non-hollow NC (e.g., [Ag25(SR)18]-), and vice versa. Our study reveals that the complete LE of the hollow [Ag44(SPhF)30]4- NCs (–SPhF: 4-fluorobenzenethiolate) with incoming 2,4-dimethylbenzenethiol (HSPhMe2) induced distortions in the Ag44 structure forming the non-hollow [Ag25(SPhMe2)18]- by a disproportionation mechanism. While the reverse reaction of [Ag25(SPhMe2)18]- with HSPhF prompted an unusual dimerization of Ag25, followed by a rearrangement step that reproduces the original [Ag44(SPhF)30]4-. Remarkably, both the forward and the backward reactions proceed through similar size intermediates that seem to be governed by the boundary conditions set by the thermodynamic and electronic stability of the hollow and non-hollow metal cores. Furthermore, the resizing of NCs highlights the surprisingly long-range effect of the ligands which are felt by atoms far deep in the metal core, thus opening a new path for controlling the structural evolution of nanoparticles.

  7. BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination.

    Science.gov (United States)

    Chen, Fan; Yan, Qinying; Yu, Yang; Wu, Mei X

    2017-06-10

    Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle

    International Nuclear Information System (INIS)

    Xiang, Zhuolin; Yen, Shih-Cheng; Zhang, Songsong; Lee, Chengkuo; Xue, Ning; Sun, Tao; Tsang, Wei Mong; Liao, Lun-De; Thakor, Nitish V

    2014-01-01

    The ultra-thin flexible polyimide neural probe can reduce the glial sheath growth on the probe body while its flexibility can minimize the micromotion between the probe and brain tissue. To provide sufficient stiffness for penetration purposes, we developed a drawing lithography technology for uniform maltose coating to make the maltose-coated polyimide neural probe become a stiff microneedle. The coating thicknesses under different temperature and the corresponding stiffness are studied. It has been proven that the coated maltose is dissolved by body fluids after implantation for a few seconds. Moreover, carbon nanotubes are coated on the neural probe recording electrodes to improve the charge delivery ability and reduce the impedance. Last but not least, the feasibility and recording characteristic of this ultra-thin polyimide neural probe embedded in a maltose-coated microneedle are further demonstrated by in vivo tests. (paper)

  9. Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle

    Science.gov (United States)

    Xiang, Zhuolin; Yen, Shih-Cheng; Xue, Ning; Sun, Tao; Mong Tsang, Wei; Zhang, Songsong; Liao, Lun-De; Thakor, Nitish V.; Lee, Chengkuo

    2014-06-01

    The ultra-thin flexible polyimide neural probe can reduce the glial sheath growth on the probe body while its flexibility can minimize the micromotion between the probe and brain tissue. To provide sufficient stiffness for penetration purposes, we developed a drawing lithography technology for uniform maltose coating to make the maltose-coated polyimide neural probe become a stiff microneedle. The coating thicknesses under different temperature and the corresponding stiffness are studied. It has been proven that the coated maltose is dissolved by body fluids after implantation for a few seconds. Moreover, carbon nanotubes are coated on the neural probe recording electrodes to improve the charge delivery ability and reduce the impedance. Last but not least, the feasibility and recording characteristic of this ultra-thin polyimide neural probe embedded in a maltose-coated microneedle are further demonstrated by in vivo tests.

  10. Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature

    Science.gov (United States)

    Vassilieva, Elena V.; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T.; Esser, E. Stein; Pewin, Winston P.; Pulit-Penaloza, Joanna A.; Prausnitz, Mark R.; Compans, Richard W.; Skountzou, Ioanna

    2015-01-01

    Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study we evaluated the immunogenicity of H1N1, H3N2 and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25°C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by SRID assay and immune responses to vaccination in BALB/c mice. After a single immunization all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least three months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability. PMID:25895053

  11. The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Rouphael, Nadine G; Paine, Michele; Mosley, Regina; Henry, Sebastien; McAllister, Devin V; Kalluri, Haripriya; Pewin, Winston; Frew, Paula M; Yu, Tianwei; Thornburg, Natalie J; Kabbani, Sarah; Lai, Lilin; Vassilieva, Elena V; Skountzou, Ioanna; Compans, Richard W; Mulligan, Mark J; Prausnitz, Mark R

    2017-08-12

    Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat

  12. Study of functional viability of SU-8-based microneedles for neural applications

    International Nuclear Information System (INIS)

    Fernández, Luis J; Altuna, Ane; Tijero, Maria; Vilares, Roman; Berganzo, Javier; Blanco, F J; Gabriel, Gemma; Villa, Rosa; Rodríguez, Manuel J; Batlle, Montse

    2009-01-01

    This paper presents the design, fabrication, packaging and first test results of SU-8-based microneedles for neural applications. By the use of photolithography, sputtering and bonding techniques, polymer needles with integrated microchannels and electrodes have been successfully fabricated. The use of photolithography for the patterning of the fluidic channel integrated in the needle allows the design of multiple outlet ports at the needle tip, minimizing the possibility of being blocked by the tissue. Furthermore, the flexibility of the polymer reduces the risk of fracture and tissue damage once the needle is inserted, while it is still rigid enough to allow a perfect insertion into the neural tissue. Fluidic and electric characterization of the microneedles has shown their viability for drug delivery and monitoring in neural applications. First drug delivery tests in ex vivo tissue demonstrated the functional viability of the needle to deliver drugs to precise points. Furthermore, in vivo experiments have demonstrated lower associated damages during insertion than those by stereotaxic standard needles

  13. Fabrication of Flexible Microneedle Array Electrodes for Wearable Bio-Signal Recording

    Directory of Open Access Journals (Sweden)

    Lei Ren

    2018-04-01

    Full Text Available Laser-direct writing (LDW and magneto-rheological drawing lithography (MRDL have been proposed for the fabrication of a flexible microneedle array electrode (MAE for wearable bio-signal monitoring. Conductive patterns were directly written onto the flexible polyethylene terephthalate (PET substrate by LDW. The microneedle array was rapidly drawn and formed from the droplets of curable magnetorheological fluid with the assistance of an external magnetic field by MRDL. A flexible MAE can maintain a stable contact interface with curved human skin due to the flexibility of the PET substrate. Compared with Ag/AgCl electrodes and flexible dry electrodes (FDE, the electrode–skin interface impedance of flexible MAE was the minimum even after a 50-cycle bending test. Flexible MAE can record electromyography (EMG, electroencephalography (EEG and static electrocardiography (ECG signals with good fidelity. The main features of the dynamic ECG signal recorded by flexible MAE are the most distinguishable with the least moving artifacts. Flexible MAE is an attractive candidate electrode for wearable bio-signal monitoring.

  14. Sodium alginate microneedle arrays mediate the transdermal delivery of bovine serum albumin.

    Directory of Open Access Journals (Sweden)

    Yusuf K Demir

    Full Text Available BACKGROUND: The "poke and release" strategy for the delivery of macromolecules using polymeric microneedle (MN is of great importance because it eliminates microneedle reuse, the risks of biohazardous sharps and cross contamination, and it requires no special disposal mechanism. The main objective of this study was the determination of the stability and delivery of bovine serum albumin (BSA that was transported across human skin via sodium alginate (SA microneedle arrays (MNs and SA needle free patches using two different analytical methods. METHODOLOGY AND FINDINGS: The capability of two analytical methods, the bicinchoninic acid (BCA assay and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE, to precisely detect and quantify BSA within different types of polymeric MNs was assessed. The ex vivo protein release of BSA across dermatomed human abdominal skin from 10 w/w SA MNs was compared to that from needle-free patches using Franz diffusion cells. The developed applicator was mechanically characterized using a Texture Analyzer. The patch mold and its components were fabricated using a rapid prototyping machine. CONCLUSIONS/SIGNIFICANCE: The BCA method was able to precisely detect BSA that had been loaded into SA MNs. However, the use of SDS-PAGE as the analytical method resulted in significantly different amounts of BSA recovered from differently conditioned polymeric MNs. The permeation of BSA across dermatomed human abdominal skin by SA MNs, which were composed of 100 pyramidal needles, increased by approximately 15.4 fold compared to the permeation obtained with SA needle-free patches. The ease of use of the applicator during the release studies was also demonstrated, as was its mechanical characterization.

  15. Microneedle arrays coated with charge reversal pH-sensitive copolymers improve antigen presenting cells-homing DNA vaccine delivery and immune responses.

    Science.gov (United States)

    Duong, Huu Thuy Trang; Kim, Nak Won; Thambi, Thavasyappan; Giang Phan, V H; Lee, Min Sang; Yin, Yue; Jeong, Ji Hoon; Lee, Doo Sung

    2018-01-10

    Successful delivery of a DNA vaccine to antigen-presenting cells and their subsequent stimulation of CD4 + and CD8 + T cell immunity remains an inefficient process. In general, the delivery of prophylactic vaccines is mainly mired by low transfection efficacy, poor immunogenicity, and safety issues from the materials employed. Currently, several strategies have been exploited to improve immunogenicity, but an effective strategy for safe and pain-free delivery of DNA vaccines is complicated. Herein, we report the rapid delivery of polyplex-based DNA vaccines using microneedle arrays coated with a polyelectrolyte multilayer assembly of charge reversal pH-responsive copolymer and heparin. The charge reversal pH-responsive copolymer, composed of oligo(sulfamethazine)-b-poly(ethylene glycol)-b-poly(amino urethane) (OSM-b-PEG-b-PAEU), was used as a triggering layer in the polyelectrolyte multilayer assembly on microneedles. Charge reversal characteristics of this copolymer, that is, the OSM-b-PEG-b-PAEU copolymer exhibit, positive charge at low pH (pH4.03) and becoming negative charge when exposed to physiological pH conditions (pH7.4), allowing the facile assembly and disassembly of polyelectrolyte multilayers. The electrostatic repulsion between heparin and OSM-b-PEG-b-PAEU charge reversal copolymer triggered the release of DNA vaccines. DNA vaccines laden on microneedles are effectively transfected into RAW 264.7 macrophage cells in vitro. Vaccination of BALB/c mice by DNA vaccine-loaded microneedle arrays coated with a polyelectrolyte multilayer generated antigen-specific robust immune responses. These findings provide potential strategy of charge reversal pH-responsive copolymers coated microneedles for DNA vaccine delivery. Copyright © 2017. Published by Elsevier B.V.

  16. Review of applications of microneedling in dermatology

    Directory of Open Access Journals (Sweden)

    Iriarte C

    2017-08-01

    Full Text Available Christopher Iriarte,1 Olabola Awosika,2 Monica Rengifo-Pardo,1,2 Alison Ehrlich1,2 1George Washington University School of Medicine and Health Sciences, Washington, DC, USA; 2Department of Dermatology, The George Washington Medical Faculty Associates, Washington, DC, USA Abstract: Microneedling (MN is a novel therapeutic modality in dermatology. Through physical trauma from needle penetration, MN induces a wound healing cascade with minimal damage to the epidermis. This allows for enhancement in the absorption of mainstay topical therapies across the thick stratum corneum. MN has become increasingly utilized over the last several years as it is a relatively simple procedure that is cost-effective, well tolerated, and offers both cosmetic and therapeutic benefits. The ability to treat localized areas of disease has led to numerous studies gauging its potential in focal diseases of inflammation, dyschromia, and photodamage. This review discusses the principles and evidence behind the expanding applications of MN. It has shown promising results as an adjuvant therapy for enhanced drug delivery in the treatment of atrophic scars, alopecia, actinic keratoses, and disorders of pigmentation such as melasma. The efficacy in treatment of vitiligo remains limited. Overall, the procedure has few adverse sequelae compared to other therapies, is highly efficacious, and is a viable resurfacing option for skin of color. Future research is needed to determine the frequency, interval, and specific device settings that foster optimal results. Additionally, large controlled trials are needed to shed light on the utility of MN as an evidence-based regimen for the treatment of various dermatologic conditions. Keywords: microneedling, scars, acne, alopecia, hyperpigmentation, actinic keratosis

  17. Hollow-Core Fiber Lamp

    Science.gov (United States)

    Yi, Lin (Inventor); Tjoelker, Robert L. (Inventor); Burt, Eric A. (Inventor); Huang, Shouhua (Inventor)

    2016-01-01

    Hollow-core capillary discharge lamps on the millimeter or sub-millimeter scale are provided. The hollow-core capillary discharge lamps achieve an increased light intensity ratio between 194 millimeters (useful) and 254 millimeters (useless) light than conventional lamps. The capillary discharge lamps may include a cone to increase light output. Hollow-core photonic crystal fiber (HCPCF) may also be used.

  18. Long-term Nasal and Peri-oral Tightening by a Single Fractional Noninsulated Microneedle Radiofrequency Treatment.

    Science.gov (United States)

    Tanaka, Yohei

    2017-02-01

    Background: The skin tightening effects induced by non-insulated microneedle radiofrequency have proved long-lasting. Our previous three-dimensional volumetric assessment showed significant facial tightening for up to six months. However, nasal and peri-oral tightening effects lasted longer. The objective of this study was to investigate the distribution of the long-term volumetric reduction in facial area induced by a single fractional non-insulated microneedle radiofrequency treatment. Methods: Fifteen Asian patients underwent full facial skin tightening using a sharply tapered non-insulated microneedle radiofrequency applicator with a novel fractionated pulse mode. Three-dimensional volumetric assessments were performed at six and 12 months post-treatment. Patients rated their satisfaction using a 5-point scale at each follow up. Results: Objective assessments with superimposed three-dimensional color images showed significant volumetric reduction in the nasal and peri-oral areas at 12 months post-treatment in all patients. Median volumetric reductions at six and 12 months post-treatment were 13.1 and 12.3ml, respectively. All of the patients were satisfied with their results 12 months post-treatment. Side effects were not observed. Conclusions: This single fractional NIMNRF treatment provided long-lasting nasal and peri-oral tightening as shown via 3D volumetric assessment. Moreover, NIMNRF produced minimal complications, downtime, and few side effects. This approach provides safe and effective treatment of skin tightening.

  19. Clinical and Histologic Effects of Fractional Microneedling Radiofrequency Treatment on Rosacea.

    Science.gov (United States)

    Park, Seon Yong; Kwon, Hyuck Hoon; Yoon, Ji Young; Min, Seonguk; Suh, Dae Hun

    2016-12-01

    Fractional microneedling radiofrequency (FMR) is an emerging treatment modality, but its effect on rosacea has not been studied yet. To investigate the potential impact of FMR treatment on clinical improvement and histologic changes in rosacea patients. A 12-week, prospective, randomized, split-face clinical trial was conducted. Two sessions of FMR were performed on one side of the cheeks with 4-week interval and the other side remained untreated. Erythema index from DermaSpectrometer and a* value from Spectrophotometer CM-2002 were measured at each visit for the objective measurement of erythema. Histologic analysis of skin samples was also carried out. Clinical evaluation and photometric measurement revealed the reduction of redness in the treated side compared with untreated side and baseline. Erythema index decreased 13.6% and a* value decreased 6.8% at Week 12 compared with baseline. Reduced expression of markers related to inflammation, innate immunity, and angiogenesis was observed in immunohistochemical staining of tissue obtained after FMR treatment. Fractional microneedling radiofrequency treatment showed modest clinical and histologic improvement of rosacea, and it might be used as an alternative or in combination with other treatment methods.

  20. Closed hollow bulb obturator--one-step fabrication: a clinical report.

    Science.gov (United States)

    Buzayan, Muaiyed M; Ariffin, Yusnidar T; Yunus, Norsiah

    2013-10-01

    A method is described for the fabrication of a closed hollow bulb obturator prosthesis using a hard thermoforming splint material and heat-cured acrylic resin. The technique allowed the thickness of the thermoformed bulb to be optimized for weight reduction, while the autopolymerized seal area was covered in heat-cured acrylic resin, thus eliminating potential leakage and discoloration. This technique permits the obturator prosthesis to be processed to completion from the wax trial denture without additional laboratory investing, flasking, and processing. © 2013 by the American College of Prosthodontists.

  1. Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice

    NARCIS (Netherlands)

    Ding, Z.; Verbaan, F. J.; Bivas-Benita, M.; Bungener, L.; Huckriede, A.; van den Berg, D. J.; Kersten, G.; Bouwstra, J. A.

    2009-01-01

    Transcutaneous immunization (TCI) is limited by poor permeation of macromolecules across the skin. Microneedle arrays form transient conduits and enhance the transport of vaccine molecules across the skin barrier without pain sensation. Here we investigated in mouse the immune responses after TO

  2. Non-insulated smooth motion, micro-needles RF fractional treatment for wrinkle reduction and lifting of the lower face: International study.

    Science.gov (United States)

    Gold, Michael; Taylor, Mark; Rothaus, Kenneth; Tanaka, Yohei

    2016-10-01

    Skin aging occurs through both intrinsic and extrinsic processes. Fractional radiofrequency (RF) with a microneedling array is the newest form of fractional therapy to be useful in treating aging skin. The current study utilized a noninsulated fractional RF microneedling system. This multicenter clinical trial saw 49 patients complete 3 monthly treatments with the new fractional RF microneedling treatments and be followed for 3 months following their last treatment. Pain during treatment was recorded as well as overall improvement using a GAIS scale. Adverse events were also noted. Forty-nine patients completed all of the treatments and follow-ups. Mild to moderate erythema were reported immediately after treatment which lasted up to 12 hours after the treatment. Pain, as measured on a 1-10 VAS, was noted to 4, on average. The average Fitzpatrick's wrinkle scale score at baseline was 5.04 ± 1.22, 1 month after 3 treatments 3.829 ± 1.69 and 3 months after 3 treatments 3.5 ± 1.66. These results are statistically highly significant (correlated T-test, P skin tightening and skin lifting were also observed. No unusual adverse events were noted throughout the course of the study. This multicenter study showed significant wrinkle reduction, skin tightening, and lifting of the mid and lower face with the noninsulated fractional RF microneedling system. Lasers Surg. Med. 48:727-733, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device

    Directory of Open Access Journals (Sweden)

    Robyn P Hickerson

    2013-01-01

    Full Text Available Despite the development of potent siRNAs that effectively target genes responsible for skin disorders, translation to the clinic has been hampered by inefficient delivery through the stratum corneum barrier and into the live cells of the epidermis. Although hypodermic needles can be used to transport siRNA through the stratum corneum, this approach is limited by pain caused by the injection and the small volume of tissue that can be accessed by each injection. The use of microneedle arrays is a less painful method for siRNA delivery, but restricted payload capacity limits this approach to highly potent molecules. To address these challenges, a commercially available motorized microneedle array skin delivery device was evaluated. This device combines the positive elements of both hypodermic needles and microneedle array technologies with little or no pain to the patient. Application of fluorescently tagged self-delivery (sd-siRNA to both human and murine skin resulted in distribution throughout the treated skin. In addition, efficient silencing (78% average reduction of reporter gene expression was achieved in a transgenic fluorescent reporter mouse skin model. These results indicate that this device effectively delivers functional sd-siRNA with an efficiency that predicts successful clinical translation.

  4. Thickness and Closure Kinetics of the Suprachoroidal Space Following Microneedle Injection of Liquid Formulations.

    Science.gov (United States)

    Chiang, Bryce; Venugopal, Nitin; Grossniklaus, Hans E; Jung, Jae Hwan; Edelhauser, Henry F; Prausnitz, Mark R

    2017-01-01

    To determine the effect of injection volume and formulation of a microneedle injection into the suprachoroidal space (SCS) on SCS thickness and closure kinetics. Microneedle injections containing 25 to 150 μL Hanks' balanced salt solution (HBSS) were performed in the rabbit SCS ex vivo. Distribution of SCS thickness was measured by ultrasonography and three-dimensional (3D) cryo-reconstruction. Microneedle injections were performed in the rabbit SCS in vivo using HBSS, Discovisc, and 1% to 5% carboxymethyl cellulose (CMC) in HBSS. Ultrasonography was used to track SCS thickness over time. Increasing HBSS injection volume increased the area of expanded SCS, but did not increase SCS thickness ex vivo. With SCS injections in vivo, the SCS initially expanded to thicknesses of 0.43 ± 0.06 mm with HBSS, 1.5 ± 0.4 mm with Discovisc, and 0.69 to 2.1 mm with 1% to 5% CMC. After injection with HBSS, Discovisc, and 1% CMC solution, the SCS collapsed to baseline with time constants of 19 minutes, 6 hours, and 2.4 days, respectively. In contrast, injections with 3% to 5% CMC solution resulted in SCS expansion to 2.3 to 2.8 mm over the course of 2.8 to 9.1 hours, after which the SCS collapsed to baseline with time constants of 4.5 to 9.2 days. With low-viscosity formulations, SCS expands to a thickness that remains roughly constant, independent of the volume of fluid injected. Increasing injection fluid viscosity significantly increased SCS thickness. Expansion of the SCS is hypothesized to be controlled by a balance between the viscous forces of the liquid formulation and the resistive biomechanical forces of the tissue.

  5. Preparation of TiO2 hollow fibers using poly(vinylidene fluoride) hollow fiber microfiltration membrane as a template

    International Nuclear Information System (INIS)

    Lu Haiqiang; Zhang Lixiong; Xing Weihong; Wang Huanting; Xu Nanping

    2005-01-01

    TiO 2 hollow fibers were successfully prepared by using poly(vinylidene fluoride) hollow fiber microfiltration membrane as a template. The preparation procedure includes repeated impregnation of the TiO 2 precursor in the pores of the polymeric membrane, and calcination to burn off the template, producing the TiO 2 hollow fibers. The TiO 2 hollow fibers were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). TiO 2 hollow fibers with other structures, such as honeycomb monolith and spring, were also prepared by preshaping the polymeric membranes into the honeycomb structure and spring, respectively. The phase structure of the TiO 2 hollow fibers could be readily adjusted by changing the calcination temperature

  6. Hollow Micro-/Nanostructures: Synthesis and Applications

    KAUST Repository

    Lou, Xiong Wen (David)

    2008-11-03

    Hollow micro-nanostructures are of great interest in many current and emerging areas of technology. Perhaps the best-known example of the former is the use of fly-ash hollow particles generated from coal power plants as partial replacement for Portland cement, to produce concrete with enhanced strength and durability. This review is devoted to the progress made in the last decade in synthesis and applications of hollow micro-nanostructures. We present a comprehensive overview of synthetic strategies for hollow structures. These strategies are broadly categorized into four themes, which include well-established approaches, such as conventional hard-templating and soft-templating methods, as well as newly emerging methods based on sacrificial templating and template-free synthesis. Success in each has inspired multiple variations that continue to drive the rapid evolution of the field. The Review therefore focuses on the fundamentals of each process, pointing out advantages and disadvantages where appropriate. Strategies for generating more complex hollow structures, such as rattle-type and nonspherical hollow structures, are also discussed. Applications of hollow structures in lithium batteries, catalysis and sensing, and biomedical applications are reviewed. © 2008 WILEY-VCH Verlag GmbH & Co. KGaA,.

  7. Low loss hollow optical-waveguide connection from atmospheric pressure to ultra-high vacuum

    Energy Technology Data Exchange (ETDEWEB)

    Ermolov, A.; Mak, K. F.; Tani, F.; Hölzer, P.; Travers, J. C. [Max Planck Institute for the Science of Light, Günther-Scharowsky-Str. 1, 91058 Erlangen (Germany); Russell, P. St. J. [Max Planck Institute for the Science of Light, Günther-Scharowsky-Str. 1, 91058 Erlangen (Germany); Department of Physics, University of Erlangen-Nuremberg, Günther-Scharowsky-Str. 1, 91058 Erlangen (Germany)

    2013-12-23

    A technique for optically accessing ultra-high vacuum environments, via a photonic-crystal fiber with a long small hollow core, is described. The small core and the long bore enable a pressure ratio of over 10{sup 8} to be maintained between two environments, while permitting efficient and unimpeded delivery of light, including ultrashort optical pulses. This delivery can be either passive or can encompass nonlinear optical processes such as optical pulse compression, deep UV generation, supercontinuum generation, or other useful phenomena.

  8. The Effect of Microneedle Thickness on Pain During Minimally Invasive Facial Procedures: A Clinical Study.

    Science.gov (United States)

    Sezgin, Billur; Ozel, Bora; Bulam, Hakan; Guney, Kirdar; Tuncer, Serhan; Cenetoglu, Seyhan

    2014-07-01

    Minimally invasive procedures are becoming increasingly popular because they require minimal downtime and are effective for achieving a more youthful appearance. The choice of needle for minimally invasive procedures can be a major factor in the patient's comfort level, which in turn affects the physician's comfort level. In this comparative study, the authors assessed levels of pain and bruising after participants were injected with 30-gauge or 33-gauge (G) microneedles, which are commonly used for minimally invasive injection procedures. Twenty healthy volunteers were recruited for this prospective study. Eight injection points (4 on each side of the face) were determined for each patient. All participants received injections of saline with both microneedles in a randomized, blinded fashion. Levels of pain and bruising were assessed and analyzed for significance. The highest level of pain was in the malar region, and the lowest level was in the glabella. Although all pain scores were lower for the 33-G microneedle, the difference was significant only for the forehead. Because most minimally invasive procedures require multiple injections during the same sitting, the overall procedure was evaluated as well. Assessment of the multiple-injection process demonstrated a significant difference in pain level, favoring the 33-G needle. Although the difference in bruising was not statistically significant between the 2 needles, the degree of bruising was lower with the 33-G needle. For procedures that involve multiple injections to the face (such as mesotherapy and injection of botulinum toxin A), thinner needles result in less pain, making the overall experience more comfortable for the patient and the physician. 3. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

  9. Comparative efficacy and patient preference of topical anaesthetics in dermatological laser treatments and skin microneedling

    Directory of Open Access Journals (Sweden)

    Yi Zhen Chiang

    2015-01-01

    Full Text Available Background: Topical anaesthetics are effective for patients undergoing superficial dermatological and laser procedures. Our objective was to compare the efficacy and patient preference of three commonly used topical anaesthetics: (2.5% lidocaine/2.5% prilocaine cream (EMLA ® , 4% tetracaine gel (Ametop TM and 4% liposomal lidocaine gel (LMX4 ® in patients undergoing laser procedures and skin microneedling. Settings and Design: This was a prospective, double-blind study of patients undergoing laser and skin microneedling procedures at a laser unit in a tertiary referral dermatology centre. Materials and Methods: All 29 patients had three topical anaesthetics applied under occlusion for 1 hour prior to the procedure, at different treatment sites within the same anatomical zone. A self-assessment numerical pain rating scale was given to each patient to rate the pain during the procedure and each patient was asked to specify their preferred choice of topical anaesthetic at the end of the procedure. Statistical Analysis: Parametric data (mean pain scores and frequency of topical anaesthetic agent of choice were compared using the paired samples t-test. A P-value of ≤0.05 was considered as statistically significant. Results and Conclusions: Patients reported a mean (±SD; 95% confidence interval pain score of 5 (±2.58; 3.66-6.46 with Ametop TM , 4.38 (±2.53; 2.64-4.89 with EMLA ® and 3.91 (±1.95; 2.65-4.76 with LMX4 ® . There was no statistically significant difference in pain scores between the different topical anaesthetics. The majority of patients preferred LMX4 ® as their choice of topical anaesthetic for dermatological laser and skin microneedling procedures.

  10. Fabrication of Composite Microneedle Array Electrode for Temperature and Bio-Signal Monitoring.

    Science.gov (United States)

    Sun, Yiwei; Ren, Lei; Jiang, Lelun; Tang, Yong; Liu, Bin

    2018-04-13

    Body temperature and bio-signals are important health indicators that reflect the human health condition. However, monitoring these indexes is inconvenient and time-consuming, requires various instruments, and needs professional skill. In this study, a composite microneedle array electrode (CMAE) was designed and fabricated. It simultaneously detects body temperature and bio-signals. The CMAE consists of a 6 × 6 microneedles array with a height of 500 μm and a base diameter of 200 μm. Multiple insertion experiments indicate that the CMAE possesses excellent mechanical properties. The CMAE can pierce porcine skin 100 times without breaking or bending. A linear calibration relationship between temperature and voltage are experimentally obtained. Armpit temperature (35.8 °C) and forearm temperature (35.3 °C) are detected with the CMAE, and the measurements agree well with the data acquired with a clinical thermometer. Bio-signals including EII, ECG, and EMG are recorded and compared with those obtained by a commercial Ag/AgCl electrode. The CMAE continuously monitors bio-signals and is more convenient to apply because it does not require skin preparation and gel usage. The CMAE exhibits good potential for continuous and repetitive monitoring of body temperature and bio-signals.

  11. Fabrication of Composite Microneedle Array Electrode for Temperature and Bio-Signal Monitoring

    Directory of Open Access Journals (Sweden)

    Yiwei Sun

    2018-04-01

    Full Text Available Body temperature and bio-signals are important health indicators that reflect the human health condition. However, monitoring these indexes is inconvenient and time-consuming, requires various instruments, and needs professional skill. In this study, a composite microneedle array electrode (CMAE was designed and fabricated. It simultaneously detects body temperature and bio-signals. The CMAE consists of a 6 × 6 microneedles array with a height of 500 μm and a base diameter of 200 μm. Multiple insertion experiments indicate that the CMAE possesses excellent mechanical properties. The CMAE can pierce porcine skin 100 times without breaking or bending. A linear calibration relationship between temperature and voltage are experimentally obtained. Armpit temperature (35.8 °C and forearm temperature (35.3 °C are detected with the CMAE, and the measurements agree well with the data acquired with a clinical thermometer. Bio-signals including EII, ECG, and EMG are recorded and compared with those obtained by a commercial Ag/AgCl electrode. The CMAE continuously monitors bio-signals and is more convenient to apply because it does not require skin preparation and gel usage. The CMAE exhibits good potential for continuous and repetitive monitoring of body temperature and bio-signals.

  12. Computer simulations of laser driven implosion of seeded hollow pellets

    International Nuclear Information System (INIS)

    Larsen, J.T.

    1974-01-01

    The use of a hollow pellet of high r/Δ r permits the successful generation of thermonuclear energy for a moderate laser input. Incorporation of a medium-z material is required for minimization of plasma instabilities and thus suppression of pathologically hot electrons. Designs of this nature are capable of giving yield ratios in excess of 20 for 100 kJ input. It is also likely that a lower-z material may be advantageous to minimize the x-rays radiation into the DT, but this will be at the sacrifice of using less laser power to remain below the plasma instability threshold. (U.S.)

  13. In vivo histological evaluation of non-insulated microneedle radiofrequency applicator with novel fractionated pulse mode.

    Science.gov (United States)

    Harth, Yoram; Frank, Ido

    2013-12-01

    Microneedle radiofrequency is a novel method that allows non-thermal penetration of the epidermis followed by RF coagulation in selected depth of the dermis surrounded by zone of non-coagulative volumetric heating. The first generation of Microneedle RF applicators used insulated needles. These treatments were limited by a few factors, including low volume of dermal heating, lack of effect in the papillary dermis and pinpoint bleeding during the treatment. The system tested in this study (EndyMed PRO, Intensif applicator, EndyMed Medical, Cesarea, Israel) utilizes special extra sharp tapered non-insulated microneedles and a special pulse mode, allowing full coagulation during treatment and higher effective volume of dermal heat. After Ethics Committee approval, one female pig (Type Large white X Landrace, 34 Kg) was chosen for the study. The animal was anesthetized using Ketamine, Xylazin and Isofluran. The EndyMed PRO, Intensif applicator (was used for treatment with different needle depth penetration (1 mm-3.5 mm) and in multiple energy settings. Six mm punch biopsies were harvested for histological analysis at the following time points: immediately after the treatment, 4 days after the treatment and 14 days after the treatment. H&E and Masson-Trichrome stains were processed. Visual inspection of the treated skin, immediately after the treatment, revealed arrays of pinpoint erythematous papules surrounded by undamaged epidermal tissue. Treatment field showed no sign of bleeding. Mild to moderate Erythema and Edema developed a few minutes after the treatment, varying according to the total energy delivered. The histologies taken 4-day after therapy showed in all energy settings, dry micro crusts over the treatment zones, with full healing of epidermis. In the 14-day specimens there was a replacement of the crusts/debris by a normal looking stratum corneum with complete healing of epidermis and dermis. The current in vivo study confirms that the EndyMed PRO

  14. Method for the production of fabricated hollow microspheroids

    Science.gov (United States)

    Wickramanayake, Shan; Luebke, David R.

    2015-06-09

    The method relates to the fabrication of a polymer microspheres comprised of an asymmetric layer surrounding a hollow interior. The fabricated hollow microsphere is generated from a nascent hollow microsphere comprised of an inner core of core fluid surrounded by a dope layer of polymer dope, where the thickness of the dope layer is at least 10% and less than 50% of the diameter of the inner core. The nascent hollow microsphere is exposed to a gaseous environment, generating a vitrified hollow microsphere, which is subsequently immersed in a coagulation bath. Solvent exchange produces a fabricated hollow microsphere comprised of a densified outer skin surrounding a macroporous inner layer, which surrounds a hollow interior. In an embodiment, the polymer is a polyimide or a polyamide-imide, and the non-solvent in the core fluid and the coagulation bath is water. The fabricated hollow microspheres are particularly suited as solvent supports for gas separation processes.

  15. Complex Hollow Nanostructures: Synthesis and Energy-Related Applications.

    Science.gov (United States)

    Yu, Le; Hu, Han; Wu, Hao Bin; Lou, Xiong Wen David

    2017-04-01

    Hollow nanostructures offer promising potential for advanced energy storage and conversion applications. In the past decade, considerable research efforts have been devoted to the design and synthesis of hollow nanostructures with high complexity by manipulating their geometric morphology, chemical composition, and building block and interior architecture to boost their electrochemical performance, fulfilling the increasing global demand for renewable and sustainable energy sources. In this Review, we present a comprehensive overview of the synthesis and energy-related applications of complex hollow nanostructures. After a brief classification, the design and synthesis of complex hollow nanostructures are described in detail, which include hierarchical hollow spheres, hierarchical tubular structures, hollow polyhedra, and multi-shelled hollow structures, as well as their hybrids with nanocarbon materials. Thereafter, we discuss their niche applications as electrode materials for lithium-ion batteries and hybrid supercapacitors, sulfur hosts for lithium-sulfur batteries, and electrocatalysts for oxygen- and hydrogen-involving energy conversion reactions. The potential superiorities of complex hollow nanostructures for these applications are particularly highlighted. Finally, we conclude this Review with urgent challenges and further research directions of complex hollow nanostructures for energy-related applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs).

    Science.gov (United States)

    Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W

    2011-09-15

    Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. New Fabrication Method of Three-Electrode System on Cylindrical Capillary Surface as a Flexible Implantable Microneedle

    Science.gov (United States)

    Yang, Zhuoqing; Zhang, Yi; Itoh, Toshihiro; Maeda, Ryutaro

    2013-04-01

    In this present paper, a three-electrode system has been fabricated and integrated on the cylindrical polymer capillary surface by micromachining technology, which could be used as a flexible and implantable microneedle for glucose sensor application in future. A UV lithography system is successfully developed for high resolution alignment on cylindrical substrates. The multilayer alignment exposure for cylindrical polymer capillary substrate is for the first time realized utilizing the lithography system. The ±1 μm alignment precision has been realized on the 330 μm-outer diameter polymer capillary surface, on which the three-electrode structure consisting of two platinum electrodes and one Ag/AgCl reference electrode has been fabricated. The fabricated whole device as microneedle for glucose sensor application has been also characterized in 1 mol/L KCl and 0.02 mol/L K3Fe(CN)6 mix solution. The measured cyclic voltammetry curve shows that the prepared three-electrode system has a good redox property.

  18. Wireless sEMG System with a Microneedle-Based High-Density Electrode Array on a Flexible Substrate.

    Science.gov (United States)

    Kim, Minjae; Gu, Gangyong; Cha, Kyoung Je; Kim, Dong Sung; Chung, Wan Kyun

    2017-12-30

    Surface electromyography (sEMG) signals reflect muscle contraction and hence, can provide information regarding a user's movement intention. High-density sEMG systems have been proposed to measure muscle activity in small areas and to estimate complex motion using spatial patterns. However, conventional systems based on wet electrodes have several limitations. For example, the electrolyte enclosed in wet electrodes restricts spatial resolution, and these conventional bulky systems limit natural movements. In this paper, a microneedle-based high-density electrode array on a circuit integrated flexible substrate for sEMG is proposed. Microneedles allow for high spatial resolution without requiring conductive substances, and flexible substrates guarantee stable skin-electrode contact. Moreover, a compact signal processing system is integrated with the electrode array. Therefore, sEMG measurements are comfortable to the user and do not interfere with the movement. The system performance was demonstrated by testing its operation and estimating motion using a Gaussian mixture model-based, simplified 2D spatial pattern.

  19. Hollow bunches production

    CERN Document Server

    Hancock, S

    2017-01-01

    Hollow bunches address the issue of high-brightnessbeams suffering from transverse emittance growth in a strongspace charge regime. During the Proton Synchrotron (PS)injection plateau, the negative space charge tune shift canpush the beam onto theQy=6integer resonance. Modify-ing the longitudinal bunch profile in order to reduce the peakline charge density alleviates the detrimental impact of spacecharge. To this end we first produce longitudinally hollowphase space distributions in the PS Booster by exciting aparametric resonance with the phase loop feedback system.These inherently flat bunches are then transferred to the PS,where the beam becomes less prone to the emittance growthcaused by the integer resonance.During the late 2016 machine development sessions inthe PS Booster we profited from solved issues from 2015and managed to reliably extract hollow bunches of1.3eVsmatched longitudinal area. Furthermore, first results to cre-ate hollow bunches with larger longitudinal emittances to-wards the LHC Inject...

  20. Anti-obesity effect of a novel caffeine-loaded dissolving microneedle patch in high-fat diet-induced obese C57BL/6J mice.

    Science.gov (United States)

    Dangol, Manita; Kim, Suyong; Li, Cheng Guo; Fakhraei Lahiji, Shayan; Jang, Mingyu; Ma, Yonghao; Huh, Inyoung; Jung, Hyungil

    2017-11-10

    Natural products such as caffeine have been found to be effective in reducing body weight through lipolysis. Here, we report the successful loading of caffeine onto dissolving microneedle following inhibition of its crystal growth by hyaluronic acid (HA), the matrix material of the dissolving microneedle (DMN). Further, the anti-obesity activity of caffeine was evaluated in high-fat diet-induced obese C57BL/6J mice. After 6weeks of caffeine loaded dissolving microneedle patch (CMP) administration, lipolysis improved significantly as shown by leptin and adiponectin activity, which resulted in considerable weight loss of about 12.8±0.75% in high-fat diet-induced obese mice. Comparison of the levels of triglyceride, total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol after CMP administration with the initial levels in obese mice indicated significant anti-obesity activity of CMP. These findings suggested that a novel CMP with an increased amount of caffeine loaded onto DMN has therapeutic activity against obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Glucose-Responsive Insulin Delivery by Microneedle-Array Patches Loaded with Hypoxia-Sensitive Vesicles.

    Science.gov (United States)

    Yu, Jicheng; Zhang, Yuqi; Gu, Zhen

    2017-01-01

    In this chapter, we describe the preparation of glucose-responsive vesicles (GRVs) and the fabrication of GRV-loaded microneedle-array patches for insulin delivery. The GRVs were formed of hypoxia-sensitive hyaluronic acid (HS-HA), the synthesis of which is presented in detail. We also describe the procedure to evaluate the in vivo efficacy of this smart patch in a mouse model of chemically induced type 1 diabetes through transcutaneous administration.

  2. Evidence of fire resistance of hollow-core slabs

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl; Sørensen, Lars Schiøtt; Giuliani, Luisa

    is therefore going on in the Netherlands about the fire resistance of hollow-core slabs. In 2014 the producers of hollow-core slabs have published a report of a project called Holcofire containing a collection of 162 fire tests on hollow-core slabs giving for the first time an overview of the fire tests made....... The present paper analyses the evidence now available for assessment of the fire resistance of extruded hollow-core slabs. The 162 fire tests from the Holcofire report are compared against the requirements for testing from the product standard for hollow-core slabs EN1168 and knowledge about the possible......Hollow-core slabs have during the past 50 years comprised a variety of different structures with different cross-sections and reinforcement. At present the extruded hollow-core slabs without cross-reinforcement in the bottom flange and usually round or oval longitudinal channels (holes...

  3. Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis.

    Science.gov (United States)

    Amodwala, Sejal; Kumar, Praveen; Thakkar, Hetal P

    2017-06-15

    The long term administration of Meloxicam for the management of arthritis, a chronic disorder, results in gastrointestinal disturbances leading to poor patient compliance. Considering the favorable molecular weight, therapeutic dose, biological half-life and log P value of meloxicam for transdermal delivery, its fast dissolving microneedle patch, with an ability to breach the stratum corneum and efficiently deliver the cargo to deeper skin layers, were developed. Microneedle patch of low molecular weight polyvinyl alcohol and polyvinylpyrrolidone was prepared using Polydimethylsiloxane micromolds. The ratio of polyvinyl alcohol to polyvinyl pyrrolidone and solid content of matrix solution was optimized to achieve maximum needle strength. The optimized batch was extensively evaluated for in vitro dissolution, drug release, stability, ex vivo skin permeation/deposition, histopathology and in vivo pharmacodynamic study. The patch containing 9:1 polyvinyl alcohol to polyvinylpyrrolidone ratio with 50% solid content had shown maximum axial needle fracture force (0.9N) suitable for penetrating the skin. The optimized batch was found to be fast dissolving and released almost 100% drug in 60min following dissolution controlled kinetics. The formulation showed a significant drug deposition within skin (63.37%) and an improved transdermal flux (1.60μg/cm 2 /h) with a 2.58 fold enhancement in permeation as compared to plain drug solution. The formulation showed a comparable anti-inflammatory activity in rats when compared to its existing approved marketed oral tablet. Histopathology and stability evaluations demonstrated acceptable safety and shelf-life of the developed formulation. The successful verification of safety, efficacy and stability of microneedle patch advocated the suitability of the formulation for transdermal use. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The Electrospun Ceramic Hollow Nanofibers

    Directory of Open Access Journals (Sweden)

    Shahin Homaeigohar

    2017-11-01

    Full Text Available Hollow nanofibers are largely gaining interest from the scientific community for diverse applications in the fields of sensing, energy, health, and environment. The main reasons are: their extensive surface area that increases the possibilities of engineering, their larger accessible active area, their porosity, and their sensitivity. In particular, semiconductor ceramic hollow nanofibers show greater space charge modulation depth, higher electronic transport properties, and shorter ion or electron diffusion length (e.g., for an enhanced charging–discharging rate. In this review, we discuss and introduce the latest developments of ceramic hollow nanofiber materials in terms of synthesis approaches. Particularly, electrospinning derivatives will be highlighted. The electrospun ceramic hollow nanofibers will be reviewed with respect to their most widely studied components, i.e., metal oxides. These nanostructures have been mainly suggested for energy and environmental remediation. Despite the various advantages of such one dimensional (1D nanostructures, their fabrication strategies need to be improved to increase their practical use. The domain of nanofabrication is still advancing, and its predictable shortcomings and bottlenecks must be identified and addressed. Inconsistency of the hollow nanostructure with regard to their composition and dimensions could be one of such challenges. Moreover, their poor scalability hinders their wide applicability for commercialization and industrial use.

  5. Evolution of nickel sulfide hollow spheres through topotactic transformation

    Science.gov (United States)

    Wei, Chengzhen; Lu, Qingyi; Sun, Jing; Gao, Feng

    2013-11-01

    In this study, a topotactic transformation route was proposed to synthesize single-crystalline β-NiS hollow spheres with uniform phase and morphology evolving from polycrystalline α-NiS hollow spheres. Uniform polycrystalline α-NiS hollow spheres were firstly prepared with thiourea and glutathione as sulfur sources under hydrothermal conditions through the Kirkendall effect. By increasing the reaction temperature the polycrystalline α-NiS hollow spheres were transformed to uniform β-NiS hollow spheres. The β-NiS crystals obtained through the topotactic transformation route not only have unchanged morphology of hollow spheres but are also single-crystalline in nature. The as-prepared NiS hollow spheres display a good ability to remove the organic pollutant Congo red from water, which makes them have application potential in water treatment.In this study, a topotactic transformation route was proposed to synthesize single-crystalline β-NiS hollow spheres with uniform phase and morphology evolving from polycrystalline α-NiS hollow spheres. Uniform polycrystalline α-NiS hollow spheres were firstly prepared with thiourea and glutathione as sulfur sources under hydrothermal conditions through the Kirkendall effect. By increasing the reaction temperature the polycrystalline α-NiS hollow spheres were transformed to uniform β-NiS hollow spheres. The β-NiS crystals obtained through the topotactic transformation route not only have unchanged morphology of hollow spheres but are also single-crystalline in nature. The as-prepared NiS hollow spheres display a good ability to remove the organic pollutant Congo red from water, which makes them have application potential in water treatment. Electronic supplementary information (ESI) available: XRD patterns; SEM images and TEM images. See DOI: 10.1039/c3nr03371f

  6. Study on an alternating current electrothermal micropump for microneedle-based fluid delivery systems

    Science.gov (United States)

    Zhang, Rumi; Jullien, Graham A.; Dalton, Colin

    2013-07-01

    In this paper, we report on a modeling study of an AC electrothermal (ACET) micropump with high operating pressures as well as fast flow rates. One specific application area is for fluid delivery using microneedle arrays which require higher pressures and faster flow rates than have been previously reported with ACET devices. ACET is very suitable for accurate actuation and control of fluid flow, since the technique has been shown to be very effective in high conductivity fluids and has the ability to create a pulsation free flow. However, AC electrokinetic pumps usually can only generate low operating pressures of 1 to 100 Pa, where flow reversal is likely to occur with an external load. In order to realize a high performance ACET micropump for continuous fluid delivery, applying relatively high AC operating voltages (20 to 36 Vrms) to silicon substrate ACET actuators and using long serpentine channel allows the boosting of operating pressure as well as increasing the flow rates. Fast pumping flow rates (102-103 nl/s) and high operating pressures (1-12 kPa) can be achieved by applying both methods, making them of significant importance for continuous fluid delivery applications using microneedle arrays and other such biomedical devices.

  7. Hollow core plasma channel generation

    International Nuclear Information System (INIS)

    Quast, Heinrich Martin

    2018-03-01

    The use of a hollow plasma channel in plasma-based acceleration has beneficial properties for the acceleration of electron and positron bunches. In the scope of the FLASHForward facility at DESY, the generation of such a plasma structure is examined. Therefore, the generation of a ring-shaped laser intensity profile with different techniques is analyzed. From the obtained intensity profiles the electron density of a hollow plasma channel is simulated in the focal region. Different parameters are scanned to understand their influence on the electron density distribution - an important parameter being, for example, the radius of the central region of the channel. In addition to the simulations, experiments are presented, during which a laser pulse is transformed into a hollow beam with a spiral phase plate. Subsequently, it forms a plasma during the interaction with hydrogen, where the plasma is imaged with interferometry. For energies above 0.9 mJ a hollow plasma structure can be observed at the location of first plasma formation.

  8. Hollow rods for the oil producing industry

    Energy Technology Data Exchange (ETDEWEB)

    Khalimova, L M; Elyasheva, M A

    1970-01-01

    Hollow sucker rods have several advantages over conventional ones. The hollow rods actuate the well pump and at the same time conduct produced fluids to surface. When paraffin deposition occurs, it can be minimized by injecting steam, hot oil or hot water into the hollow rod. Other chemicals, such as demulsifiers, scale inhibitors, corrosion inhibitors, etc., can also be placed in the well through the hollow rods. This reduces cost of preventive treatments, reduces number of workovers, increases oil production, and reduces cost of oil. Because the internal area of the rod is small, the passing liquids have a high velocity and thereby carry sand and dirt out of the well. This reduces pump wear between the piston and the plunger. Specifications of hollow rods, their operating characteristics, and results obtained with such rods under various circumstances are described.

  9. Effect of Osmotic Pressure on the Stability of Whole Inactivated Influenza Vaccine for Coating on Microneedles.

    Directory of Open Access Journals (Sweden)

    Hyo-Jick Choi

    Full Text Available Enveloped virus vaccines can be damaged by high osmotic strength solutions, such as those used to protect the vaccine antigen during drying, which contain high concentrations of sugars. We therefore studied shrinkage and activity loss of whole inactivated influenza virus in hyperosmotic solutions and used those findings to improve vaccine coating of microneedle patches for influenza vaccination. Using stopped-flow light scattering analysis, we found that the virus underwent an initial shrinkage on the order of 10% by volume within 5 s upon exposure to a hyperosmotic stress difference of 217 milliosmolarity. During this shrinkage, the virus envelope had very low osmotic water permeability (1 - 6×10-4 cm s-1 and high Arrhenius activation energy (Ea = 15.0 kcal mol-1, indicating that the water molecules diffused through the viral lipid membranes. After a quasi-stable state of approximately 20 s to 2 min, depending on the species and hypertonic osmotic strength difference of disaccharides, there was a second phase of viral shrinkage. At the highest osmotic strengths, this led to an undulating light scattering profile that appeared to be related to perturbation of the viral envelope resulting in loss of virus activity, as determined by in vitro hemagglutination measurements and in vivo immunogenicity studies in mice. Addition of carboxymethyl cellulose effectively prevented vaccine activity loss in vitro and in vivo, believed to be due to increasing the viscosity of concentrated sugar solution and thereby reducing osmotic stress during coating of microneedles. These results suggest that hyperosmotic solutions can cause biphasic shrinkage of whole inactivated influenza virus which can damage vaccine activity at high osmotic strength and that addition of a viscosity enhancer to the vaccine coating solution can prevent osmotically driven damage and thereby enable preparation of stable microneedle coating formulations for vaccination.

  10. Transmission properties of hollow-core photonic bandgap fibers

    DEFF Research Database (Denmark)

    Falk, Charlotte Ijeoma; Hald, Jan; Petersen, Jan C.

    2010-01-01

    Variations in optical transmission of four types of hollow-core photonic bandgap fibers are measured as a function of laser frequency. These variations influence the potential accuracy of gas sensors based on molecular spectroscopy in hollow-core fibers.......Variations in optical transmission of four types of hollow-core photonic bandgap fibers are measured as a function of laser frequency. These variations influence the potential accuracy of gas sensors based on molecular spectroscopy in hollow-core fibers....

  11. Silicon microneedle formation using modified mask designs based on convex corner undercut

    Science.gov (United States)

    Wilke, N.; Morrissey, A.

    2007-02-01

    In this work, we present microneedle fabrication using the mechanism of silicon convex corner undercutting for modified etch masks in aqueous KOH solution (29% KOH, 79 °C). The presented modified mask designs include three different shapes, as well as different compensation structures applied to a square mask shape. We have found that square mask shapes present an optimum needle structure in contrast to circular or diamond shapes. The use of compensation structures facilitates an increase in needle density of 33-50% over that otherwise achieved.

  12. A novel synthesis of micrometer silica hollow sphere

    International Nuclear Information System (INIS)

    Pan Wen; Ye Junwei; Ning Guiling; Lin Yuan; Wang Jing

    2009-01-01

    Silica microcapsules (hollow spheres) were synthesized successfully by a novel CTAB-stabilized water/oil emulsion system mediated hydrothermal method. The addition of urea to a solution of aqueous phase was an essential step of the simple synthetic procedure of silica hollow spheres, which leads to the formation of silica hollow spheres with smooth shell during hydrothermal process. The intact hollow spheres were obtained by washing the as-synthesized solid products with distilled water to remove the organic components. A large amount of silanol groups were retained in the hollow spheres by this facile route without calcination. The morphologies and optical properties of the product were characterized by transmission electron microscopy, scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy. Furthermore, on the basis of a series of SEM observations, phenomenological elucidation of a mechanism for the growth of the silica hollow spheres has been presented

  13. Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery.

    Science.gov (United States)

    Li, Jiyu; Liu, Bin; Zhou, Yingying; Chen, Zhipeng; Jiang, Lelun; Yuan, Wei; Liang, Liang

    2017-01-01

    Microneedle arrays (MA) have been extensively investigated in recent decades for transdermal drug delivery due to their pain-free delivery, minimal skin trauma, and reduced risk of infection. However, porous MA received relatively less attention due to their complex fabrication process and ease of fracturing. Here, we present a titanium porous microneedle array (TPMA) fabricated by modified metal injection molding (MIM) technology. The sintering process is simple and suitable for mass production. TPMA was sintered at a sintering temperature of 1250°C for 2 h. The porosity of TPMA was approximately 30.1% and its average pore diameter was about 1.3 μm. The elements distributed on the surface of TPMA were only Ti and O, which may guarantee the biocompatibility of TPMA. TPMA could easily penetrate the skin of a human forearm without fracture. TPMA could diffuse dry Rhodamine B stored in micropores into rabbit skin. The cumulative permeated flux of calcein across TPMA with punctured skin was 27 times greater than that across intact skin. Thus, TPMA can continually and efficiently deliver a liquid drug through open micropores in skin.

  14. Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery.

    Directory of Open Access Journals (Sweden)

    Jiyu Li

    Full Text Available Microneedle arrays (MA have been extensively investigated in recent decades for transdermal drug delivery due to their pain-free delivery, minimal skin trauma, and reduced risk of infection. However, porous MA received relatively less attention due to their complex fabrication process and ease of fracturing. Here, we present a titanium porous microneedle array (TPMA fabricated by modified metal injection molding (MIM technology. The sintering process is simple and suitable for mass production. TPMA was sintered at a sintering temperature of 1250°C for 2 h. The porosity of TPMA was approximately 30.1% and its average pore diameter was about 1.3 μm. The elements distributed on the surface of TPMA were only Ti and O, which may guarantee the biocompatibility of TPMA. TPMA could easily penetrate the skin of a human forearm without fracture. TPMA could diffuse dry Rhodamine B stored in micropores into rabbit skin. The cumulative permeated flux of calcein across TPMA with punctured skin was 27 times greater than that across intact skin. Thus, TPMA can continually and efficiently deliver a liquid drug through open micropores in skin.

  15. Skin Vaccination against Rotavirus Using Microneedles: Proof of Concept in Gnotobiotic Piglets.

    Directory of Open Access Journals (Sweden)

    Yuhuan Wang

    Full Text Available Live-attenuated oral rotavirus (RV vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV using the human rotavirus strain CDC-9 (G1P[8] through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.

  16. Skin Vaccination against Rotavirus Using Microneedles: Proof of Concept in Gnotobiotic Piglets.

    Science.gov (United States)

    Wang, Yuhuan; Vlasova, Anastasia; Velasquez, Daniel E; Saif, Linda J; Kandasamy, Sukumar; Kochba, Efrat; Levin, Yotam; Jiang, Baoming

    2016-01-01

    Live-attenuated oral rotavirus (RV) vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV) using the human rotavirus strain CDC-9 (G1P[8]) through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID) unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM) administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn) piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH)3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.

  17. Microneedle Coating Techniques for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rita Haj-Ahmad

    2015-11-01

    Full Text Available Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

  18. Hollow nanocrystals and method of making

    Science.gov (United States)

    Alivisatos, A Paul [Oakland, CA; Yin, Yadong [Moreno Valley, CA; Erdonmez, Can Kerem [Berkeley, CA

    2011-07-05

    Described herein are hollow nanocrystals having various shapes that can be produced by a simple chemical process. The hollow nanocrystals described herein may have a shell as thin as 0.5 nm and outside diameters that can be controlled by the process of making.

  19. Formation of Uniform Hollow Silica microcapsules

    Science.gov (United States)

    Yan, Huan; Kim, Chanjoong

    2013-03-01

    Microcapsules are small containers with diameters in the range of 0.1 - 100 μm. Mesoporous microcapsules with hollow morphologies possess unique properties such as low-density and high encapsulation capacity, while allowing controlled release by permeating substances with a specific size and chemistry. Our process is a one-step fabrication of monodisperse hollow silica capsules with a hierarchical pore structure and high size uniformity using double emulsion templates obtained by the glass-capillary microfluidic technique to encapsulate various active ingredients. These hollow silica microcapsules can be used as biomedical applications such as drug delivery and controlled release.

  20. Microring embedded hollow polymer fiber laser

    Energy Technology Data Exchange (ETDEWEB)

    Linslal, C. L., E-mail: linslal@gmail.com; Sebastian, S.; Mathew, S.; Radhakrishnan, P.; Nampoori, V. P. N.; Girijavallabhan, C. P.; Kailasnath, M. [International School of Photonics, Cochin University of Science and Technology, Cochin 22 (India)

    2015-03-30

    Strongly modulated laser emission has been observed from rhodamine B doped microring resonator embedded in a hollow polymer optical fiber by transverse optical pumping. The microring resonator is fabricated on the inner wall of a hollow polymer fiber. Highly sharp lasing lines, strong mode selection, and a collimated laser beam are observed from the fiber. Nearly single mode lasing with a side mode suppression ratio of up to 11.8 dB is obtained from the strongly modulated lasing spectrum. The microring embedded hollow polymer fiber laser has shown efficient lasing characteristics even at a propagation length of 1.5 m.

  1. Space Charge Mitigation With Longitudinally Hollow Bunches

    CERN Multimedia

    Oeftiger, Adrian; Rumolo, Giovanni

    2016-01-01

    Hollow longitudinal phase space distributions have a flat profile and hence reduce the impact of transverse space charge. Dipolar parametric excitation with the phase loop feedback systems provides such hollow distributions under reproducible conditions. We present a procedure to create hollow bunches during the acceleration ramp of CERN’s PS Booster machine with minimal changes to the operational cycle. The improvements during the injection plateau of the downstream Proton Synchrotron are assessed in comparison to standard parabolic bunches.

  2. Hollow nanotubular toroidal polymer microrings.

    Science.gov (United States)

    Lee, Jiyeong; Baek, Kangkyun; Kim, Myungjin; Yun, Gyeongwon; Ko, Young Ho; Lee, Nam-Suk; Hwang, Ilha; Kim, Jeehong; Natarajan, Ramalingam; Park, Chan Gyung; Sung, Wokyung; Kim, Kimoon

    2014-02-01

    Despite the remarkable progress made in the self-assembly of nano- and microscale architectures with well-defined sizes and shapes, a self-organization-based synthesis of hollow toroids has, so far, proved to be elusive. Here, we report the synthesis of polymer microrings made from rectangular, flat and rigid-core monomers with anisotropically predisposed alkene groups, which are crosslinked with each other by dithiol linkers using thiol-ene photopolymerization. The resulting hollow toroidal structures are shape-persistent and mechanically robust in solution. In addition, their size can be tuned by controlling the initial monomer concentrations, an observation that is supported by a theoretical analysis. These hollow microrings can encapsulate guest molecules in the intratoroidal nanospace, and their peripheries can act as templates for circular arrays of metal nanoparticles.

  3. Hollow spheres: crucial building blocks for novel nanostructures and nanophotonics

    Directory of Open Access Journals (Sweden)

    Zhong Kuo

    2018-03-01

    Full Text Available In this review, we summarize the latest developments in research specifically derived from the unique properties of hollow microspheres, in particular, hollow silica spheres with uniform shells. We focus on applications in nanosphere (colloidal lithography and nanophotonics. The lithography from a layer of hollow spheres can result in nanorings, from a multilayer in unique nano-architecture. In nanophotonics, disordered hollow spheres can result in antireflection coatings, while ordered colloidal crystals (CCs of hollow spheres exhibit unique refractive index enhancement upon infiltration, ideal for optical sensing. Furthermore, whispering gallery mode (WGM inside the shell of hollow spheres has also been demonstrated to enhance light absorption to improve the performance of solar cells. These applications differ from the classical applications of hollow spheres, based only on their low density and large surface area, such as catalysis and chemical sensing. We provide a brief overview of the synthesis and self-assembly approaches of the hollow spheres. We elaborate on their unique optical features leading to defect mode lasing, optomicrofluidics, and the existence of WGMs inside shell for light management. Finally, we provide a perspective on the direction towards which future research relevant to hollow spheres might be directed.

  4. Hollow spheres: crucial building blocks for novel nanostructures and nanophotonics

    Science.gov (United States)

    Zhong, Kuo; Song, Kai; Clays, Koen

    2018-03-01

    In this review, we summarize the latest developments in research specifically derived from the unique properties of hollow microspheres, in particular, hollow silica spheres with uniform shells. We focus on applications in nanosphere (colloidal) lithography and nanophotonics. The lithography from a layer of hollow spheres can result in nanorings, from a multilayer in unique nano-architecture. In nanophotonics, disordered hollow spheres can result in antireflection coatings, while ordered colloidal crystals (CCs) of hollow spheres exhibit unique refractive index enhancement upon infiltration, ideal for optical sensing. Furthermore, whispering gallery mode (WGM) inside the shell of hollow spheres has also been demonstrated to enhance light absorption to improve the performance of solar cells. These applications differ from the classical applications of hollow spheres, based only on their low density and large surface area, such as catalysis and chemical sensing. We provide a brief overview of the synthesis and self-assembly approaches of the hollow spheres. We elaborate on their unique optical features leading to defect mode lasing, optomicrofluidics, and the existence of WGMs inside shell for light management. Finally, we provide a perspective on the direction towards which future research relevant to hollow spheres might be directed.

  5. Development of tree hollows in pedunculate oak (Quercus robur)

    OpenAIRE

    Ranius, Thomas; Niklasson, Mats; Berg, Niclas

    2009-01-01

    Many invertebrates, birds and mammals are dependent on hollow trees. For landscape planning that aims at persistence of species inhabiting hollow trees it is crucial to understand the development of such trees. In this study we constructed an individual-based simulation model to predict diameter distribution and formation of hollows in oak tree populations. Based on tree-ring data from individual trees, we estimated the ages when hollow formation commences for pedunculate oak (Quercus robur) ...

  6. Method for producing small hollow spheres

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1979-01-01

    A method is described for producing small hollow spheres of glass, metal or plastic, wherein the sphere material is mixed with or contains as part of the composition a blowing agent which decomposes at high temperature (T >approx. 600 0 C). As the temperature is quickly raised, the blowing agent decomposes and the resulting gas expands from within, thus forming a hollow sphere of controllable thickness. The thus produced hollow spheres (20 to 10 3 μm) have a variety of application, and are particularly useful in the fabrication of targets for laser implosion such as neutron sources, laser fusion physics studies, and laser initiated fusion power plants

  7. SU-8-based microneedles for in vitro neural applications

    International Nuclear Information System (INIS)

    Altuna, Ane; Tijero, María; Berganzo, Javier; Salido, Rafa; Fernández, Luis J; Gabriel, Gemma; Guimerá, Anton; Villa, Rosa; Menéndez de la Prida, Liset

    2010-01-01

    This paper presents novel design, fabrication, packaging and the first in vitro neural activity recordings of SU-8-based microneedles. The polymer SU-8 was chosen because it provides excellent features for the fabrication of flexible and thin probes. A microprobe was designed in order to allow a clean insertion and to minimize the damage caused to neural tissue during in vitro applications. In addition, a tetrode is patterned at the tip of the needle to obtain fine-scale measurements of small neuronal populations within a radius of 100 µm. Impedance characterization of the electrodes has been carried out to demonstrate their viability for neural recording. Finally, probes are inserted into 400 µm thick hippocampal slices, and simultaneous action potentials with peak-to-peak amplitudes of 200–250 µV are detected.

  8. Application of a three-microneedle device for the delivery of local anesthetics

    Directory of Open Access Journals (Sweden)

    Ishikawa K

    2015-04-01

    Full Text Available Kayoko Ishikawa,1 Hidekazu Fukamizu,1 Tetsuya Takiguchi,1 Yusuke Ohta,1 Yoshiki Tokura2 1Department of Plastic and Reconstructive Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan; 2Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Purpose: We investigated the effectiveness of a newly developed device for the delivery of local anesthetics in the treatment of axillary osmidrosis and hyperhidrosis. We developed a device with three fine, stainless steel needles fabricated with a bevel angle facing outside (“three-microneedle device” [TMD] to release a drug broadly and homogeneously into tissue in the horizontal plane. Use of this device could reduce the risk of complications when transcutaneous injections are undertaken.Patients and methods: Sixteen Japanese patients were enrolled. The mean volume of lidocaine hydrochloride per unit area needed to elicit anesthesia when using a TMD was compared with that the volume required when using a conventional 27-gauge needle. The visual analog scale (VAS score of needlestick pain and injection-associated pain was also compared.Results: The mean volume of lidocaine hydrochloride per unit area to elicit anesthesia using the TMD was significantly lower than that the volume required when using the conventional 27-gauge needle. The VAS score of needlestick pain for the TMD was significantly lower than that the VAS score for the 27-gauge needle.Conclusion: These data suggest that the TMD could be useful for the delivery of local anesthetics in terms of clinical efficacy and avoidance of adverse effects. Keywords: three-microneedle device, transcutaneous drug delivery, local anesthesia, lidocaine, pain

  9. The Riddle of the Apparently Hollow Himalaya

    Indian Academy of Sciences (India)

    The Riddle of the Apparently Hollow Himalaya. Ramesh .... It was as if the Himalayas were hollow inside. ... block would be consistent with the ground elevation in such a ... Alternative models and possible preference: Many refinements of.

  10. Skin immunization by microneedle patch overcomes statin-induced suppression of immune responses to influenza vaccine.

    Science.gov (United States)

    Vassilieva, Elena V; Wang, Shelly; Li, Song; Prausnitz, Mark R; Compans, Richard W

    2017-12-19

    Recent studies indicated that in elderly individuals, statin therapy is associated with a reduced response to influenza vaccination. The present study was designed to determine effects on the immune response to influenza vaccination induced by statin administration in a mouse model, and investigate potential approaches to improve the outcome of vaccination on the background of statin therapy. We fed middle aged BALB/c mice a high fat "western" diet (WD) alone or supplemented with atorvastatin (AT) for 14 weeks, and control mice were fed with the regular rodent diet. Mice were immunized with a single dose of subunit A/Brisbane/59/07 (H1N1) vaccine, either systemically or with dissolving microneedle patches (MNPs). We observed that a greater age-dependent decline in the hemagglutinin inhibition titers occurred in systemically-immunized mice than in MNP- immunized mice. AT dampened the antibody response in the animals vaccinated by either route of vaccine delivery. However, the MNP-vaccinated AT-treated animals had ~20 times higher total antibody levels to the influenza vaccine than the systemically vaccinated group one month postvaccination. We propose that microneedle vaccination against influenza provides an approach to ameliorate the immunosuppressive effect of statin therapy observed with systemic immunization.

  11. Minimally-invasive, microneedle-array extraction of interstitial fluid for comprehensive biomedical applications: transcriptomics, proteomics, metabolomics, exosome research, and biomarker identification.

    Science.gov (United States)

    Taylor, Robert M; Miller, Philip R; Ebrahimi, Parwana; Polsky, Ronen; Baca, Justin T

    2018-01-01

    Interstitial fluid (ISF) has recently garnered interest as a biological fluid that could be used as an alternate to blood for biomedical applications, diagnosis, and therapy. ISF extraction techniques are promising because they are less invasive and less painful than venipuncture. ISF is an alternative, incompletely characterized source of physiological data. Here, we describe a novel method of ISF extraction in rats, using microneedle arrays, which provides volumes of ISF that are sufficient for downstream analysis techniques such as proteomics, genomics, and extracellular vesicle purification and analysis. This method is potentially less invasive than previously reported techniques. The limited invasiveness and larger volumes of extracted ISF afforded by this microneedle-assisted ISF extraction method provide a technique that is less stressful and more humane to laboratory animals, while also allowing for a reduction in the numbers of animals needed to acquire sufficient volumes of ISF for biomedical analysis and application.

  12. Fabrication of Metallic Microneedle by Electroplating and Sharpening of it by Electrochemical Etching

    Science.gov (United States)

    Huang, Chih-Hao; Tanaka, Takahiro; Takaoki, Yutaka; Izumi, Hayato; Takahashi, Tomokazu; Suzuki, Masato; Aoyagi, Seiji

    Aiming at the use in low-invasive medical treatments, this paper reports a fabrication of metallic microneedle, which has a three-dimensionally sharp tip. Compared to a silicon or polymer needle which we previously proposed, a metallic needle has toughness to evade breakage. Even if it is broken, it does not become small pieces thanks to its ductility, which increases the safety for a human body. A nickel needle was fabricated using electroplating, followed by sharpening it by electrochemical etching. A smooth tip surface is obtained due to electrochemical etching reactions. Sharpness and smoothness of the tip are effective for easy insertion in the viewpoint of large stress concentration and small friction, respectively. An experiment of inserting the fabricated needle into an artificial skin of silicone rubber was carried out. The resistance force during insertion was much reduced compared to that of commercial stainless needle (23 G: shank diameter 650 µm). Although a fabricated metallic needle was inserted and pulled-out for several times, it was not broken in any trial. By changing the angle between object surface and needle axis, the insertion experiments were carried out. Fabricated nickel needle was not broken for any angle, while silicon needle was broken in case the angle is small, i.e., the needle is much inclined from normal direction of the surface, which ensures the safety of metallic microneedle to human body in the viewpoint of breakage.

  13. Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design

    Directory of Open Access Journals (Sweden)

    Xavier H. M. Hartmann

    2015-11-01

    Full Text Available Arrays of microneedles (MNAs are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (npMNAs. Failure modes of ceramic npMNAs are as yet poorly understood and the question remained: is our npMNA platform technology ready for microneedle (MN assembly into patches? We investigated npMNAs by microindentation, yielding average crack fracture forces above the required insertion force for a single MN to penetrate human skin. We further developed a thumb pressure-actuated applicator-assisted npMNA insertion method, which enables anchoring of MNs in the skin by an adhesive in one handling step. Using a set of simple artificial skin models, we found a puncture efficiency of this insertion method a factor three times higher than by applying thumb pressure on the npMNA base plate directly. In addition, this new method facilitated zero MN-breakage due to a well-defined force distribution exerted onto the MNs and the closely surrounding area prior to bringing the adhesive into contact with the skin. Owing to the fact that such parameter space exists, we can conclude that npMNAs by soft lithography are a platform technology for MN assembly into a patch.

  14. Hollow metal nanostructures for enhanced plasmonics (Conference Presentation)

    Science.gov (United States)

    Genç, Aziz; Patarroyo, Javier; Sancho-Parramon, Jordi; Duchamp, Martial; Gonzalez, Edgar; Bastus, Neus G.; Houben, Lothar; Dunin-Borkowski, Rafal; Puntes, Victor F.; Arbiol, Jordi

    2016-03-01

    Complex metal nanoparticles offer a great playground for plasmonic nanoengineering, where it is possible to cover plasmon resonances from ultraviolet to near infrared by modifying the morphologies from solid nanocubes to nanoframes, multiwalled hollow nanoboxes or even nanotubes with hybrid (alternating solid and hollow) structures. We experimentally show that structural modifications, i.e. void size and final morphology, are the dominant determinants for the final plasmonic properties, while compositional variations allow us to get a fine tuning. EELS mappings of localized surface plasmon resonances (LSPRs) reveal an enhanced plasmon field inside the voids of hollow AuAg nanostructures along with a more homogeneous distributions of the plasmon fields around the nanostructures. With the present methodology and the appropriate samples we are able to compare the effects of hybridization at the nanoscale in hollow nanostructures. Boundary element method (BEM) simulations also reveal the effects of structural nanoengineering on plasmonic properties of hollow metal nanostructures. Possibility of tuning the LSPR properties of hollow metal nanostructures in a wide range of energy by modifying the void size/shell thickness is shown by BEM simulations, which reveals that void size is the dominant factor for tuning the LSPRs. As a proof of concept for enhanced plasmonic properties, we show effective label free sensing of bovine serum albumin (BSA) with some of our hollow nanostructures. In addition, the different plasmonic modes observed have also been studied and mapped in 3D.

  15. Ni hollow spheres as catalysts for methanol and ethanol electrooxidation

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Changwei [Department of Chemistry and Institute of Nanochemistry, Jinan University, Guangzhou 510632 (China); School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Hu, Yonghong; Rong, Jianhua; Liu, Yingliang [Department of Chemistry and Institute of Nanochemistry, Jinan University, Guangzhou 510632 (China); Jiang, San Ping [School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2007-08-15

    In this paper, we successfully synthesized Ni hollow spheres consisting of needle-like nickel particles by using silica spheres as template with gold nanoparticles seeding method. The Ni hollow spheres are applied to methanol and ethanol electrooxidation in alkaline media. The results show that the Ni hollow spheres give a very high activity for alcohol electrooxidation at a very low nickel loading of 0.10 mg cm{sup -2}. The current on Ni hollow spheres is much higher than that on Ni particles. The onset potential and peak potential on Ni hollow spheres are more negative than that on Ni particles for methanol and ethanol electrooxidation. The Ni hollow spheres may be of great potential in alcohol sensor and direct alcohol fuel cells. (author)

  16. Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs

    OpenAIRE

    Banks, Stan L.; Pinninti, Raghotham R.; Gill, Harvinder S.; Paudel, Kalpana S.; Crooks, Peter A.; Brogden, Nicole K.; Prausnitz, Mark R.; Stinchcomb, Audra L.

    2010-01-01

    Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. Micro...

  17. Fabrication of Closed Hollow Bulb Obturator Using Thermoplastic Resin Material

    Directory of Open Access Journals (Sweden)

    Bidhan Shrestha

    2015-01-01

    Full Text Available Purpose. Closed hollow bulb obturators are used for the rehabilitation of postmaxillectomy patients. However, the time consuming process, complexity of fabrication, water leakage, and discoloration are notable disadvantages of this technique. This paper describes a clinical report of fabricating closed hollow bulb obturator using a single flask and one time processing method for an acquired maxillary defect. Hard thermoplastic resin sheet has been used for the fabrication of hollow bulb part of the obturator. Method. After fabrication of master cast conventionally, bulb and lid part of the defect were formed separately and joined by autopolymerizing acrylic resin to form one sized smaller hollow body. During packing procedure, the defect area was loaded with heat polymerizing acrylic resin and then previously fabricated smaller hollow body was adapted over it. The whole area was then loaded with heat cure acrylic. Further processes were carried out conventionally. Conclusion. This technique uses single flask which reduces laboratory time and makes the procedure simple. The thickness of hollow bulb can be controlled and light weight closed hollow bulb prosthesis can be fabricated. It also minimizes the disadvantages of closed hollow bulb obturator such as water leakage, bacterial infection, and discoloration.

  18. Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

    Science.gov (United States)

    Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

    2017-01-01

    Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Preparation and Application of Hollow Silica/magnetic Nanocomposite Particle

    Science.gov (United States)

    Wang, Cheng-Chien; Lin, Jing-Mo; Lin, Chun-Rong; Wang, Sheng-Chang

    The hollow silica/cobalt ferrite (CoFe2O4) magnetic microsphere with amino-groups were successfully prepared via several steps, including preparing the chelating copolymer microparticles as template by soap-free emulsion polymerization, manufacturing the hollow cobalt ferrite magnetic microsphere by in-situ chemical co-precipitation following calcinations, and surface modifying of the hollow magnetic microsphere by 3-aminopropyltrime- thoxysilane via the sol-gel method. The average diameter of polymer microspheres was ca. 200 nm from transmission electron microscope (TEM) measurement. The structure of the hollow magnetic microsphere was characterized by using TEM and scanning electron microscope (SEM). The spinel-type lattice of CoFe2O4 shell layer was identified by using XRD measurement. The diameter of CoFe2O4 crystalline grains ranged from 54.1 nm to 8.5 nm which was estimated by Scherrer's equation. Additionally, the hollow silica/cobalt ferrite microsphere possesses superparamagnetic property after VSM measurement. The result of BET measurement reveals the hollow magnetic microsphere which has large surface areas (123.4m2/g). After glutaraldehyde modified, the maximum value of BSA immobilization capacity of the hollow magnetic microsphere was 33.8 mg/g at pH 5.0 buffer solution. For microwave absorption, when the hollow magnetic microsphere was compounded within epoxy resin, the maximum reflection loss of epoxy resins could reach -35dB at 5.4 GHz with 1.9 mm thickness.

  20. Microneedles: A New Frontier in Nanomedicine Delivery.

    Science.gov (United States)

    Larrañeta, Eneko; McCrudden, Maelíosa T C; Courtenay, Aaron J; Donnelly, Ryan F

    2016-05-01

    This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN.

  1. Long-term evaluation of hollow screw and hollow cylinder dental implants : Clinical and radiographic results after 10 years

    NARCIS (Netherlands)

    Telleman, Gerdien; Meijer, Henny J. A.; Raghoebar, Gerry M.

    Background: In 1988, an implant manufacturer offered a new dental implant system, with a wide choice of hollow cylinder (HC) and hollow screw (HS) implants. The purpose of this retrospective study of HS and HC implants was to evaluate clinical and radiographic parameters of peri-implant tissue and

  2. Applying ceramic nanoporous microneedle arrays as a transport interface in egg plants and an ex-vivo human skin model

    NARCIS (Netherlands)

    Verhoeven, M.L.P.M.; van Nieuwkasteele-Bystrova, Svetlana Nikolajevna; Winnubst, Aloysius J.A.; Qureshi, H.F.; de Gruijl, T.D.; Scheper, R.J.; Lüttge, Regina

    2012-01-01

    Nanoporous microneedle arrays from Al2O3 were fabricated via a micromolding process using a PDMS mold generated via a double replication process from a SU-8/Si-master as a template. Hg-porosity measurements showed that the porosity obtained was a function of the temperature used for sintering,

  3. Inkjet printing of insulin microneedles for transdermal delivery.

    Science.gov (United States)

    Ross, Steven; Scoutaris, Nicolaos; Lamprou, Dimitrios; Mallinson, David; Douroumis, Dennis

    2015-08-01

    Inkjet printing technology was used to apply insulin polymeric layers on metal microneedles for transdermal delivery. A range of various polymers such as gelatin (GLN), polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol (SOL), poly(2-ethyl-2-oxazoline) (POX) and trehalose (THL) were assessed for their capacity to form thin uniform and homogeneous layers that preserve insulin intact. Atomic force microscopy (AFM) showed homogeneous insulin-polymer layers without any phase separation while SOL demonstrated the best performance. Circular discroism (CD) analysis of rehydrated films showed that insulin's alpha helices and β-sheet were well preserved for THL and SOL. In contrast, GLN and POX insulin layers revealed small band shifts indicating possible conformational changes. Insulin release in Franz diffusion cells from MNs inserted into porcine skin showed rapid release rates for POX and GLN within the first 20 min. Inkjet printing was proved an effective approach for transdermal delivery of insulin in solid state.

  4. Synthesis of barium-strontium titanate hollow tubes using Kirkendall effect

    Science.gov (United States)

    Chen, Xuncai; Im, SangHyuk; Kim, Jinsoo; Kim, Woo-Sik

    2018-02-01

    (BaSr)TiO3 hexagonal hollow tubes was fabricated by a solid-state interfacial reaction including a Kirkendall diffusion. Using a co-precipitation and sol-gel process, a core@shell structure of (BaSr)CO3@TiO2 rods were prepared, and then converted to (BaSr)TiO3 hollow tubes at 750 °C. This was a first achievement of single-phase crystal hollow tube. Here, the inner diameter and wall thickness of hollow tube were about 700 nm and 130 nm, respectively. The fabrication of (BaSr)TiO3 hollow tubes was monitored with scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), transmission electron microscopy (TEM), and X-ray diffraction (XRD) to investigate their formation mechanism. The present synthetic approach would provide a new insight into the design and fabrication of hollow architectures of many perovskite oxides.

  5. Hollow porous-wall glass microspheres for hydrogen storage

    Science.gov (United States)

    Heung, Leung K.; Schumacher, Ray F.; Wicks, George G.

    2010-02-23

    A porous wall hollow glass microsphere is provided having a diameter range of between 1 to 200 microns, a density of between 1.0 to 2.0 gm/cc, a porous-wall structure having wall openings defining an average pore size of between 10 to 1000 angstroms, and which contains therein a hydrogen storage material. The porous-wall structure facilitates the introduction of a hydrogen storage material into the interior of the porous wall hollow glass microsphere. In this manner, the resulting hollow glass microsphere can provide a membrane for the selective transport of hydrogen through the porous walls of the microsphere, the small pore size preventing gaseous or liquid contaminants from entering the interior of the hollow glass microsphere.

  6. Evaluation of the clinical efficacy of fractional radiofrequency microneedle treatment in acne scars and large facial pores.

    Science.gov (United States)

    Cho, Soo Ick; Chung, Bo Young; Choi, Min Gyu; Baek, Ji Hwoon; Cho, Hee Jin; Park, Chun Wook; Lee, Cheol Heon; Kim, Hye One

    2012-07-01

    Fractional technology overcomes the problems of ablative lasers, such as inaccurate depth control and damage to the epidermis. Minimally invasive fractional radiofrequency microneedle devices allow for more-selective heating of the dermis. To evaluate the clinical efficacy of fractional radiofrequency microneedle (ERM) treatment in acne scars and large facial pores. Thirty patients with acne scars and large facial pores were enrolled. Bipolar radiofrequency energy was delivered to the skin through the electrodes of the FRM device. Skin lesions were evaluated according to grade of acne scars, Investigator Global Assessment of large pores, skin surface roughness, transepidermal water loss (TEWL), dermal density, microscopic and composite image, sebum measurement, and questionnaires regarding patient satisfaction. The grade of acne scars and Investigator Global Assessment of large pores improved in more than 70% of all patients. Skin surface roughness, dermal density, and microscopic and composite images also improved, whereas TEWL and sebum measurement did not change. Clinical improvement from FRM treatment appeared to be related to dermal matrix regeneration. FRM treatment may be effective in improving acne scars and facial pores. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  7. Adiabatic Rearrangement of Hollow PV Towers

    Directory of Open Access Journals (Sweden)

    Eric A Hendricks

    2010-10-01

    Full Text Available Diabatic heating from deep moist convection in the hurricane eyewall produces a towering annular structure of elevated potential vorticity (PV. This structure has been referred to as a hollow PV tower. The sign reversal of the radial gradient of PV satisfies the Charney-Stern necessary condition for combined barotropic-baroclinic instability. For thin enough annular structures, small perturbations grow exponentially, extract energy from the mean flow, and lead to hollow tower breakdown, with significant vortex structural and intensity change. The three-dimensional adiabatic rearrangements of two prototypical hurricane-like hollow PV towers (one thick and one thin are examined in an idealized framework. For both hollow towers, dynamic instability causes air parcels with high PV to be mixed into the eye preferentially at lower levels, where unstable PV wave growth rates are the largest. Little or no mixing is found to occur at upper levels. The mixing at lower and middle levels is most rapid for the breakdown of the thin hollow tower, consistent with previous barotropic results. For both hollow towers, this advective rearrangement of PV affects the tropical cyclone structure and intensity in a number of ways. First, the minimum central pressure and maximum azimuthal mean velocity simultaneously decrease, consistent with previous barotropic results. Secondly, isosurfaces of absolute angular momentum preferentially shift inward at low levels, implying an adiabatic mechanism by which hurricane eyewall tilt can form. Thirdly, a PV bridge, similar to that previously found in full-physics hurricane simulations, develops as a result of mixing at the isentropic levels where unstable PV waves grow most rapidly. Finally, the balanced mass field resulting from the PV rearrangement is warmer in the eye between 900 and 700 hPa. The location of this warming is consistent with observed warm anomalies in the eye, indicating that in certain instances the hurricane

  8. Fabrication of Micro-Needle Electrodes for Bio-Signal Recording by a Magnetization-Induced Self-Assembly Method

    Directory of Open Access Journals (Sweden)

    Keyun Chen

    2016-09-01

    Full Text Available Micro-needle electrodes (MEs have attracted more and more attention for monitoring physiological electrical signals, including electrode-skin interface impedance (EII, electromyography (EMG and electrocardiography (ECG recording. A magnetization-induced self-assembling method (MSM was developed to fabricate a microneedle array (MA. A MA coated with Ti/Au film was assembled as a ME. The fracture and insertion properties of ME were tested by experiments. The bio-signal recording performance of the ME was measured and compared with a typical commercial wet electrode (Ag/AgCl electrode. The results show that the MA self-assembled from the magnetic droplet array under the sum of gravitational surface tension and magnetic potential energies. The ME had good toughness and could easily pierce rabbit skin without being broken or buckling. When the compression force applied on the ME was larger than 2 N, ME could stably record EII, which was a lower value than that measured by Ag/AgCl electrodes. EMG signals collected by ME varied along with the contraction of biceps brachii muscle. ME could record static ECG signals with a larger amplitude and dynamic ECG signals with more distinguishable features in comparison with a Ag/AgCl electrode, therefore, ME is an alternative electrode for bio-signal monitoring in some specific situations.

  9. Recent progress in hollow sphere-based electrodes for high-performance supercapacitors

    Science.gov (United States)

    Zhao, Yan; Chen, Min; Wu, Limin

    2016-08-01

    Hollow spheres have drawn much attention in the area of energy storage and conversion, especially in high-performance supercapacitors owing to their well-defined morphologies, uniform size, low density and large surface area. And quite some significant breakthroughs have been made in advanced supercapacitor electrode materials with hollow sphere structures. In this review, we summarize and discuss the synthesis and application of hollow spheres with controllable structure and morphology as electrode materials for supercapacitors. First, we briefly introduce the fabrication strategies of hollow spheres for electrode materials. Then, we discuss in detail the recent advances in various hollow sphere-based electrode materials for supercapacitors, including single-shelled, yolk-shelled, urchin-like, double-shelled, multi-shelled, and mesoporous hollow structure-based symmetric and asymmetric supercapacitor devices. We conclude this review with some perspectives on the future research and development of the hollow sphere-based electrode materials.

  10. Recent progress in hollow sphere-based electrodes for high-performance supercapacitors.

    Science.gov (United States)

    Zhao, Yan; Chen, Min; Wu, Limin

    2016-08-26

    Hollow spheres have drawn much attention in the area of energy storage and conversion, especially in high-performance supercapacitors owing to their well-defined morphologies, uniform size, low density and large surface area. And quite some significant breakthroughs have been made in advanced supercapacitor electrode materials with hollow sphere structures. In this review, we summarize and discuss the synthesis and application of hollow spheres with controllable structure and morphology as electrode materials for supercapacitors. First, we briefly introduce the fabrication strategies of hollow spheres for electrode materials. Then, we discuss in detail the recent advances in various hollow sphere-based electrode materials for supercapacitors, including single-shelled, yolk-shelled, urchin-like, double-shelled, multi-shelled, and mesoporous hollow structure-based symmetric and asymmetric supercapacitor devices. We conclude this review with some perspectives on the future research and development of the hollow sphere-based electrode materials.

  11. Microstructure and corrosion resistance of nitrogen-rich surface layers on AISI 304 stainless steel by rapid nitriding in a hollow cathode discharge

    Science.gov (United States)

    Li, Yang; He, Yongyong; Zhang, Shangzhou; Wang, Wei; Zhu, Yijie

    2018-01-01

    Nitriding treatments have been successfully applied to austenitic stainless steels to improve their hardness and tribological properties. However, at temperatures above 450 °C, conventional plasma nitriding processes decrease the corrosion resistance due to the formation of CrN phases within the modified layer. In this work, AISI 304 austenitic stainless steels were efficiently treated by rapid plasma nitriding at a high temperature of 530 °C in a hollow cathode discharge. The enhanced ionization obtained in the hollow cathode configuration provided a high current density and, consequently, a high temperature could be attained in a short time. The nitrided layers were characterized by X-ray diffraction, scanning electron microscopy, atomic force microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. The results indicated that the dual-layer structure of the nitrided layer consists of a high-N face-centered cubic structure with a free CrN precipitate outer (top) layer and a nitrogen-expanded austenite S-phase bottom layer. The rapid nitriding-assisted hollow cathode discharge technique permits the use of high temperatures, as high as 530 °C, without promoting degradation in the corrosion resistance of stainless steel.

  12. Hollow-duct radiation delivery system investigation

    Directory of Open Access Journals (Sweden)

    Kramer D.

    2013-05-01

    Full Text Available Investigation of hollow-duct structure for high-power laser-diode-array radiation delivery into the end-pumped large-aperture gain media is reported. A ray tracing method has been used to evaluate the performance of the structure designed for maximum transmission efficiency and output beam profile homogeneity. Variable hollow-duct lengths as well as emanating angles of laser-diode-array have been taken into account.

  13. Hollow fiber liquid supported membranes

    International Nuclear Information System (INIS)

    Violante, V.

    1987-01-01

    The hollow fiber system are well known and developed in the scientific literature because of their applicability in the process separation units. The authors approach to a mathematical model for a particular hollow fiber system, usin liquid membranes. The model has been developed in order to obtain a suitable tool for a sensitivy analysis and for a scaling-up. This kind of investigation is very usefull from an engineering point of view, to get a spread range of information to build up a pilot plant from the laboratory scale

  14. Experimental study on hollow structural component by explosive welding

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Mianjun, E-mail: dmjwl@163.com [PLA University of Science and Technology, Nanjing 210007 (China); Wei, Ling, E-mail: 386006087@qq.com [Tongda College, Nanjing University of Posts and Telecommunication, Nanjing 210007 (China); Hong, Jin [PLA University of Science and Technology, Nanjing 210007 (China); Ran, Hong [Southwestern Institute of Physics, Chengdu 610041 (China); Ma, Rui; Wang, Yaohua [PLA University of Science and Technology, Nanjing 210007 (China)

    2014-12-15

    Highlights: • This paper relates to a study on a thin double-layers hollow structural component by using an explosive welding technology. • This thin double-layer hollow structural component is an indispensable component required for certain core equipment of thermonuclear experimental reactor. • An adjusted explosive welding technology for manufacturing an inconel625 hollow structural component was developed which cannot be made by common technology. • The result shows that a metallurgical bonding was realized by the ribs and slabs of the hollow sheet. • The shearing strength of bonding interface exceeds that of the parent metal. - Abstract: A large thin-walled hollow structural component with sealed channels is required for the vacuum chamber of a thermonuclear experimental reactor, with inconel625 as its fabrication material. This hollow structural component is rarely manufactured by normal machining method, and its manufacture is also problematic in the field of explosive welding. With this in mind, we developed an adjusted explosive welding technology which involves a two-step design, setting and annealing technology. The joints were evaluated using optical microscope and scanning electron microscope, and a mechanical experiment was conducted, involving micro-hardness test, cold helium leak test and hydraulic pressure test. The results showed that a metallurgical bonding was realized by the ribs and slabs, and the shearing strength of the bonding interface exceeded that of the parent metal. Hence, the hollow structural component has a good comprehensive mechanical performance and sealing property.

  15. Experimental study on hollow structural component by explosive welding

    International Nuclear Information System (INIS)

    Duan, Mianjun; Wei, Ling; Hong, Jin; Ran, Hong; Ma, Rui; Wang, Yaohua

    2014-01-01

    Highlights: • This paper relates to a study on a thin double-layers hollow structural component by using an explosive welding technology. • This thin double-layer hollow structural component is an indispensable component required for certain core equipment of thermonuclear experimental reactor. • An adjusted explosive welding technology for manufacturing an inconel625 hollow structural component was developed which cannot be made by common technology. • The result shows that a metallurgical bonding was realized by the ribs and slabs of the hollow sheet. • The shearing strength of bonding interface exceeds that of the parent metal. - Abstract: A large thin-walled hollow structural component with sealed channels is required for the vacuum chamber of a thermonuclear experimental reactor, with inconel625 as its fabrication material. This hollow structural component is rarely manufactured by normal machining method, and its manufacture is also problematic in the field of explosive welding. With this in mind, we developed an adjusted explosive welding technology which involves a two-step design, setting and annealing technology. The joints were evaluated using optical microscope and scanning electron microscope, and a mechanical experiment was conducted, involving micro-hardness test, cold helium leak test and hydraulic pressure test. The results showed that a metallurgical bonding was realized by the ribs and slabs, and the shearing strength of the bonding interface exceeded that of the parent metal. Hence, the hollow structural component has a good comprehensive mechanical performance and sealing property

  16. Engineering Porous Polymer Hollow Fiber Microfluidic Reactors for Sustainable C-H Functionalization.

    Science.gov (United States)

    He, Yingxin; Rezaei, Fateme; Kapila, Shubhender; Rownaghi, Ali A

    2017-05-17

    Highly hydrophilic and solvent-stable porous polyamide-imide (PAI) hollow fibers were created by cross-linking of bare PAI hollow fibers with 3-aminopropyl trimethoxysilane (APS). The APS-grafted PAI hollow fibers were then functionalized with salicylic aldehyde for binding catalytically active Pd(II) ions through a covalent postmodification method. The catalytic activity of the composite hollow fiber microfluidic reactors (Pd(II) immobilized APS-grafted PAI hollow fibers) was tested via heterogeneous Heck coupling reaction of aryl halides under both batch and continuous-flow reactions in polar aprotic solvents at high temperature (120 °C) and low operating pressure. X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma (ICP) analyses of the starting and recycled composite hollow fibers indicated that the fibers contain very similar loadings of Pd(II), implying no degree of catalyst leaching from the hollow fibers during reaction. The composite hollow fiber microfluidic reactors showed long-term stability and strong control over the leaching of Pd species.

  17. Review of Synthetic Methods to Form Hollow Polymer Nanocapsules

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Madeline T. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-03-13

    Syntactic foams have grown in interest due to the widened range of applications because of their mechanical strength and high damage tolerance. In the past, hollow glass or ceramic particles were used to create the pores. This paper reviews literature focused on the controlled synthesis of hollow polymer spheres with diameters ranging from 100 –200 nm. By using hollow polymer spheres, syntactic foams could reach ultra-low densities.

  18. Hollow cathode for positive ion sources

    International Nuclear Information System (INIS)

    Schechter, D.E.; Kim, J.; Tsai, C.C.

    1979-01-01

    Development to incorporate hollow cathodes into high power ion sources for neutral beam injection systems is being pursued. Hollow tube LaB 6 -type cathodes, similar to a UCLA design, have been constructed and tested in several ORNL ion source configurations. Results of testing include arc discharge parameters of >1000 and 500 amps for 0.5 and 10 second pulse lengths, respectively. Details of cathode construction and additional performance results are discussed

  19. Polyazole hollow fiber membranes for direct contact membrane distillation

    KAUST Repository

    Maab, Husnul; Alsaadi, Ahmad Salem; Francis, Lijo; Livazovic, Sara; Ghaffour, NorEddine; Amy, Gary L.; Nunes, Suzana Pereira

    2013-01-01

    Porous hollow fiber membranes were fabricated from fluorinated polyoxadiazole and polytriazole by a dry-wet spinning method for application in desalination of Red Sea water by direct contact membrane distillation (DCMD). The data were compared with commercially available hollow fiber MD membranes prepared from poly(vinylidene fluoride). The membranes were characterized by electron microscopy, liquid entry pressure (LEP), and pore diameter measurements. Finally, the hollow fiber membranes were tested for DCMD. Salt selectivity as high as 99.95% and water fluxes as high as 35 and 41 L m -2 h-1 were demonstrated, respectively, for polyoxadiazole and polytriazole hollow fiber membranes, operating at 80 C feed temperature and 20 C permeate. © 2013 American Chemical Society.

  20. Polyazole hollow fiber membranes for direct contact membrane distillation

    KAUST Repository

    Maab, Husnul

    2013-08-07

    Porous hollow fiber membranes were fabricated from fluorinated polyoxadiazole and polytriazole by a dry-wet spinning method for application in desalination of Red Sea water by direct contact membrane distillation (DCMD). The data were compared with commercially available hollow fiber MD membranes prepared from poly(vinylidene fluoride). The membranes were characterized by electron microscopy, liquid entry pressure (LEP), and pore diameter measurements. Finally, the hollow fiber membranes were tested for DCMD. Salt selectivity as high as 99.95% and water fluxes as high as 35 and 41 L m -2 h-1 were demonstrated, respectively, for polyoxadiazole and polytriazole hollow fiber membranes, operating at 80 C feed temperature and 20 C permeate. © 2013 American Chemical Society.

  1. Boron nitride hollow nanospheres: Synthesis, formation mechanism and dielectric property

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, B.; Tang, X.H. [School of Materials Science and Engineering, Harbin Institute of Technology at Weihai, Weihai 264209 (China); Huang, X.X., E-mail: swliza@hit.edu.cn [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Xia, L. [School of Materials Science and Engineering, Harbin Institute of Technology at Weihai, Weihai 264209 (China); Zhang, X.D. [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Wang, C.J. [School of Materials Science and Engineering, Harbin Institute of Technology at Weihai, Weihai 264209 (China); Wen, G.W., E-mail: g.wen@hit.edu.cn [School of Materials Science and Engineering, Harbin Institute of Technology at Weihai, Weihai 264209 (China); School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China)

    2015-04-15

    Highlights: • BN hollow nanospheres are fabricated in large scale via a new CVD method. • Morphology and structure are elucidated by complementary analytical techniques. • Formation mechanism is proposed based on experimental observations. • Dielectric properties are investigated in the X-band microwave frequencies. • BN hollow nanospheres show lower dielectric loss than regular BN powders. - Abstract: Boron nitride (BN) hollow nanospheres have been successfully fabricated by pyrolyzing vapors decomposed from ammonia borane (NH{sub 3}BH{sub 3}) at 1300 °C. The final products have been extensively characterized by X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. The BN hollow nanospheres were ranging from 100 to 300 nm in diameter and around 30–100 nm in thickness. The internal structure of the products was found dependent on the reaction temperatures. A possible formation mechanism of the BN hollow nanospheres was proposed on the basis of the experimental observations. Dielectric measurements in the X-band microwave frequencies (8–12 GHz) showed that the dielectric loss of the paraffin filled by the BN hollow nanospheres was lower than that filled by regular BN powders, which indicated that the BN hollow nanospheres could be potentially used as low-density fillers for microwave radomes.

  2. High performance methanol-oxygen fuel cell with hollow fiber electrode

    Science.gov (United States)

    Lawson, Daniel D. (Inventor); Ingham, John D. (Inventor)

    1983-01-01

    A methanol/air-oxygen fuel cell including an electrode formed by open-ended ion-exchange hollow fibers having a layer of catalyst deposited on the inner surface thereof and a first current collector in contact with the catalyst layer. A second current collector external of said fibers is provided which is immersed along with the hollow fiber electrode in an aqueous electrolyte body. Upon passage of air or oxygen through the hollow fiber electrode and introduction of methanol into the aqueous electrolyte, a steady current output is obtained. Two embodiments of the fuel cell are disclosed. In the first embodiment the second metal electrode is displaced away from the hollow fiber in the electrolyte body while in the second embodiment a spiral-wrap electrode is provided about the outer surface of the hollow fiber electrode.

  3. High-performance supercapacitors based on hollow polyaniline nanofibers by electrospinning.

    Science.gov (United States)

    Miao, Yue-E; Fan, Wei; Chen, Dan; Liu, Tianxi

    2013-05-22

    Hollow polyaniline (PANI) nanofibers with controllable wall thickness are fabricated by in situ polymerization of aniline using the electrospun poly(amic acid) fiber membrane as a template. A maximum specific capacitance of 601 F g(-1) has been achieved at 1 A g(-1), suggesting the potential application of hollow PANI nanofibers for supercapacitors. The superior electrochemical performance of the hollow nanofibers is attributed to their hollow structure, thin wall thickness, and orderly pore passages, which can drastically facilitate the ion diffusion and improve the utilization of the electroactive PANI during the charge-discharge processes. Furthermore, the high flexibility of the self-standing fiber membrane template provides possibilities for the facile construction and fabrication of conducting polymers with hollow nanostructures, which may find potential applications in various high-performance electrochemical devices.

  4. Mercury - the hollow planet

    Science.gov (United States)

    Rothery, D. A.

    2012-04-01

    Mercury is turning out to be a planet characterized by various kinds of endogenous hole (discounting impact craters), which are compared here. These include volcanic vents and collapse features on horizontal scales of tens of km, and smaller scale depressions ('hollows') associated with bright crater-floor deposits (BCFD). The BCFD hollows are tens of metres deep and kilometres or less across and are characteristically flat-floored, with steep, scalloped walls. Their form suggests that they most likely result from removal of surface material by some kind of mass-wasting process, probably associated with volume-loss caused by removal (via sublimation?) of a volatile component. These do not appear to be primarily a result of undermining. Determining the composition of the high-albedo bluish surface coating in BCFDs will be a key goal for BepiColombo instruments such as MIXS (Mercury Imaging Xray Spectrometer). In contrast, collapse features are non-circular rimless pits, typically on crater floors (pit-floor craters), whose morphology suggests collapse into void spaces left by magma withdrawal. This could be by drainage of either erupted lava (or impact melt) or of shallowly-intruded magma. Unlike the much smaller-scale BCFD hollows, these 'collapse pit' features tend to lack extensive flat floors and instead tend to be close to triangular in cross-section with inward slopes near to the critical angle of repose. The different scale and morphology of BCFD hollows and collapse pits argues for quite different modes of origin. However, BCFD hollows adjacent to and within the collapse pit inside Scarlatti crater suggest that the volatile material whose loss was responsible for the growth of the hollows may have been emplaced in association with the magma whose drainage caused the main collapse. Another kind of volcanic collapse can be seen within a 25 km-wide volcanic vent outside the southern rim of the Caloris basin (22.5° N, 146.1° E), on a 28 m/pixel MDIS NAC image

  5. [Study on Hollow Brick Wall's Surface Temperature with Infrared Thermal Imaging Method].

    Science.gov (United States)

    Tang, Ming-fang; Yin, Yi-hua

    2015-05-01

    To address the characteristic of uneven surface temperature of hollow brick wall, the present research adopts soft wares of both ThermaCAM P20 and ThermaCAM Reporter to test the application of infrared thermal image technique in measuring surface temperature of hollow brick wall, and further analyzes the thermal characteristics of hollow brick wall, and building material's impact on surface temperature distribution including hollow brick, masonry mortar, and so on. The research selects the construction site of a three-story-high residential, carries out the heat transfer experiment, and further examines the exterior wall constructed by 3 different hollow bricks including sintering shale hollow brick, masonry mortar and brick masonry. Infrared thermal image maps are collected, including 3 kinds of sintering shale hollow brick walls under indoor heating in winter; and temperature data of wall surface, and uniformity and frequency distribution are also collected for comparative analysis between 2 hollow bricks and 2 kinds of mortar masonry. The results show that improving heat preservation of hollow brick aid masonry mortar can effectively improve inner wall surface temperature and indoor thermal environment; non-uniformity of surface temperature decreases from 0. 6 to 0. 4 °C , and surface temperature frequency distribution changes from the asymmetric distribution into a normal distribution under the condition that energy-saving sintering shale hollow brick wall is constructed by thermal mortar replacing cement mortar masonry; frequency of average temperature increases as uniformity of surface temperature increases. This research provides a certain basis for promotion and optimization of hollow brick wall's thermal function.

  6. Plasma generation using the hollow cathod

    International Nuclear Information System (INIS)

    Moon, K.J.

    1983-01-01

    A hollow cathode of tungsten was adapted to an University of California, Berkely, LBL bucket ion source to investigate ion density fluctuations at the extractior grid. Fluctuations in plasma ion density are observed to range between 100kHz to 2 MHz. The observed fluctuation frequencies of plasma ion density are found to be inversely proportional to the square root of ion masses. It is guessed that the plasma fluctuation are also correlated with the hollow cathode length. (Author)

  7. Hydrogel-forming microneedles increase in volume during swelling in skin, but skin barrier function recovery is unaffected

    Science.gov (United States)

    Donnelly, Ryan F.; Mooney, Karen; McCrudden, Maelíosa T.C.; Vicente-Pérez, Eva M.; Belaid, Luc; González-Vázquez, Patricia; McElnay, James C.; Woolfson, A. David

    2014-01-01

    We describe, for the first time, quantification of in-skin swelling and fluid uptake by hydrogel-forming microneedle arrays (MN) and skin barrier recovery in human volunteers. Such MN, prepared from aqueous blends of hydrolysed poly(methylvinylether/maleicanhydride) (15% w/w) and the crosslinker poly(ethyleneglycol) 10,000 daltons (7.5% w/w), were inserted into the skin of human volunteers (n = 15) to depths of approximately 300 μm by gentle hand pressure. The MN swelled in skin, taking up skin interstitial fluid, such that their mass had increased by approximately 30% after 6 hours in skin. Importantly, however, skin barrier function recovered within 24 hours post microneedle removal, regardless of how long the MN had been in skin or how much their volume had increased with swelling. Further research on closure of MN-induced micropores is required, since transepidermal water loss measurements suggested micropore closure, while optical coherence tomography indicated that MN-induced micropores had not closed over, even 24 hours after MN had been removed. There were no complaints of skin reactions, adverse events or strong views against MN use by any of the volunteers. Only some minor erythema was noted after patch removal, although this always resolved within 48 hours and no adverse events were present on follow-up. PMID:24633895

  8. Hollow density profile on electron cyclotron resonance heating JFT-2M plasma

    International Nuclear Information System (INIS)

    Yamauchi, Toshihiko; Hoshino, Katsumichi; Kawashima, Hisato; Ogawa, Toshihide; Kawakami, Tomohide; Shiina, Tomio; Ishige, Youichi

    1998-01-01

    The first hollow electron density profile in the central region on the JAERI Fusion Torus-2M (JFT-2M) is measured during electron cyclotron resonance heating (ECRH) with a TV Thomson scattering system (TVTS). The peripheral region is not hollow but is accumulated due to pump-out from the central region. The hollowness increases with time but is saturated at ∼40 ms and maintains a constant hollow ratio. The hollowness is strongly related to the steep temperature gradient of the heated zone. (author)

  9. Field electron emission from dense array of microneedles of tungsten

    International Nuclear Information System (INIS)

    Okuyama, F.; Aoyagi, M.; Kitai, T.; Ishikawa, K.

    1978-01-01

    Characteristics of field electron emission from the dense array of microneedles of tungsten prepared on a 10-μm tungsten filament were measured at an environmental pressure of approx.1 x 10 -8 Torr (1.33 x 10 -6 Pa). Electron emission was not uniform over the filament surface, but the variation of emission current with applied voltage explicitly obeyed the Fowler-Nordheim relationship. At an emission current of approx.10 -4 A, a vacuum arc was induced that led to a permanent change in current-voltage characteristic. Current fluctuation was dependent on emitter temperature and applied voltage, and the lowest fluctuation of about 4% was routinely obtained at approx.550 K and at applied voltages several percent lower than the arc-inducing voltage. Macroscopic current density amounted to approx.20-80 mA/cm 2 at the best stability

  10. HOLLOW FIBRE MEMBRANE

    NARCIS (Netherlands)

    Wessling, Matthias; Stamatialis, Dimitrios; Kopec, K.K.; Dutczak, S.M.

    2011-01-01

    The present invention relates to a process for manufacturing a hollow fibre membrane having a supporting layer and a separating layer, said process comprising: (a)extruding a spinning composition comprising a first polymer and a solvent for the first polymer through an inner annular orifice of a

  11. HOLLOW FIBRE MEMBRANE

    NARCIS (Netherlands)

    Wessling, Matthias; Stamatialis, Dimitrios; Kopec, K.K.; Dutczak, S.M.

    2013-01-01

    The present invention relates to a process for manufacturing a hollow fibre membrane having a supporting layer and a separating layer, said process comprising: (a) extruding a spinning composition comprising a first polymer and a solvent for the first polymer through an inner annular orifice of a

  12. Ocular drug delivery targeted by iontophoresis in the suprachoroidal space using a microneedle.

    Science.gov (United States)

    Jung, Jae Hwan; Chiang, Bryce; Grossniklaus, Hans E; Prausnitz, Mark R

    2018-05-10

    Treatment of many posterior-segment ocular indications would benefit from improved targeting of drug delivery to the back of the eye. Here, we propose the use of iontophoresis to direct delivery of negatively charged nanoparticles through the suprachoroidal space (SCS) toward the posterior pole of the eye. Injection of nanoparticles into the SCS of the rabbit eye ex vivo without iontophoresis led to a nanoparticle distribution mostly localized at the site of injection near the limbus and 9 mm from the limbus). Iontophoresis using a novel microneedle-based device increased posterior targeting with >30% of nanoparticles in the most posterior region of SCS. Posterior targeting increased with increasing iontophoresis current and increasing application time up to 3 min, but further increasing to 5 min was not better, probably due to the observed collapse of the SCS within 5 min after injection ex vivo. Reversing the direction of iontophoretic flow inhibited posterior targeting, with just ~5% of nanoparticles reaching the most posterior region of SCS. In the rabbit eye in vivo, iontophoresis at 0.14 mA for 3 min after injection of a 100 μL suspension of nanoparticles resulted in ~30% of nanoparticles delivered to the most posterior region of the SCS, which was consistent with ex vivo findings. The procedure was well tolerated, with only mild, transient tissue effects at the site of injection. We conclude that iontophoresis in the SCS using a microneedle has promise as a method to target ocular drug delivery within the eye, especially toward the posterior pole. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. A novel approach to fabrication of superparamagnetite hollow silica/magnetic composite spheres

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Junjie, E-mail: yuanjunjie@tongji.edu.c [School of Materials Science and Engineering, Tongji University, Shanghai 200092 (China); Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433 (China); Zhang Xiong; Qian He [School of Materials Science and Engineering, Tongji University, Shanghai 200092 (China)

    2010-08-15

    We described a method for synthesizing hollow silica/magnetic composite spheres using sulfonic acid functionalized hollow silica spheres (SAFHSS) as templates. The Fe{sub 3}O{sub 4} nanoparticles were deposited on or imbedded in the hollow silica shell by a precipitation reaction. The morphologies, composition and properties of the hollow composite spheres were characterized by transmission electron microscopy, Fourier transform infrared analysis, X-ray diffraction measurement and vibrating-sample magnetometry measurement. The results indicated crystal sizes and amount of the Fe{sub 3}O{sub 4} nanoparticles on the SAFHSS. The magnetic properties of the hollow composite spheres were controlled by adjusting the proportion between Fe{sup 2+} and Fe{sup 3+} and iron ion total concentration. When appropriate loading species were added into the system, superparamagnetite hollow composite spheres were obtained. The method also could be applicable to prepare other superparamagnetite hollow silica/ferrite composite spheres.

  14. A Facile Method and Novel Mechanism Using Microneedle-Structured PDMS for Triboelectric Generator Applications.

    Science.gov (United States)

    Trinh, Van-Long; Chung, Chen-Kuei

    2017-08-01

    The triboelectric generator (TEG) is a cost-effective, multi-fabricated, friendly mechanical-energy-harvesting device. The traditional TEG, generally formed by two triboelectric materials in multilayers or a simple pattern, generated triboelectricity as it worked in the cycling contact-separation operation. This paper demonstrates a novel, high-aspect-ratio, microneedle (MN)-structured polydimethylsiloxane (PDMS)-based triboelectric generator (MN-TEG) by means of a low-cost, simple fabrication using CO 2 laser ablation on the polymethyl methacrylate substrate and a molding process. The MN-TEG, consisting of an aluminum foil and a microneedle-structured PDMS (MN-PDMS) film, generates an output performance with an open-circuit voltage up to 102.8 V, and a short-circuit current of 43.1 µA, corresponding to the current density of 1.5 µA cm -2 . With introducing MN-PDMS into the MN-TEG, a great increase of randomly closed bending-friction-deformation (BFD) behavior of MNs leads to highly enhanced triboelectric performance of the MN-TEG. The BFD keeps increasingly on in-contact between MN with Al that results in enhancement of electrical capacitance of PDMS. The effect of aspect ratio and density of MN morphology on the output performance of MN-PDMS TEG is studied further. The MN-TEG can rapidly charge electric energy on a 0.1 µF capacitor up to 2.1 V in about 0.56 s. The MN-TEG source under tapping can light up 53 light-emitting diodes with different colors, connected in series. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Coprecipitation-assisted hydrothermal synthesis of PLZT hollow nanospheres

    International Nuclear Information System (INIS)

    Zhu, Renqiang; Zhu, Kongjun; Qiu, Jinhao; Bai, Lin; Ji, Hongli

    2010-01-01

    Lanthanum-modified lead zirconate titanate Pb 1-x La x (Zr 1-y Ti y )O 3 (PLZT) hollow nanospheres have been successfully prepared via a template-free hydrothermal method using the well-mixed coprecipitated precursors and the KOH mineralizer. The structure, composition, and morphology of the PLZT hollow nanospheres were characterized by XRD (X-ray diffraction), ICP (inductive coupled plasma emission spectrometer), FTIR (Fourier transform infrared spectra), TG/DTA (thermogravimetric analysis and differential thermal analysis), TEM (transmission electron microscopy) and SEAD (selected area diffraction). The results show that the composition and the morphology control of the PLZT products are determined by the KOH concentration. The PLZT hollow nanospheres with uniform size of about 4 nm were synthesized in the presence of 5 M KOH. The crystalline nanoparticles can be prepared at dilute KOH, in contrast to the amorphous powders prepared at concentrated KOH. Formation mechanisms of the PLZT hollow nanospheres are also discussed.

  16. Performance of different hollow fiber membranes for seawater desalination using membrane distillation

    KAUST Repository

    Francis, Lijo; Ghaffour, NorEddine; Alsaadi, Ahmad Salem; Amy, Gary L.

    2014-01-01

    Membrane distillation requires a highly porous hydrophobic membrane with low surface energy. In this paper, we compare the direct contact membrane distillation (DCMD) performances of four different types of in-house fabricated hollow fiber membranes and two different commercially available hollow fiber membranes. Hollow fiber membranes are fabricated using wet-jet phase inversion technique and the polymeric matrices used for the fabrication are polyvinylidine fluoride (PVDF) and polyvinyl chloride (PVC). Commercial hollow fiber membrane materials are made of polytetrafluoroethylene (PTFE) and polypropylene (PP). PVDF hollow fibers showed a superior performance among all the hollow fibers tested in the DCMD process and gave a water vapor flux of 31 kg m-2h-1 at a feed and coolant inlet temperatures of 80 and 20°C, respectively. Under the same conditions, the water vapor flux observed for PP, PTFE, and PVC hollow fiber membranes are 13, 11, and 6 kg m-2h-1, respectively, with 99.99% salt rejection observed for all membranes used.

  17. Performance of different hollow fiber membranes for seawater desalination using membrane distillation

    KAUST Repository

    Francis, Lijo

    2014-08-11

    Membrane distillation requires a highly porous hydrophobic membrane with low surface energy. In this paper, we compare the direct contact membrane distillation (DCMD) performances of four different types of in-house fabricated hollow fiber membranes and two different commercially available hollow fiber membranes. Hollow fiber membranes are fabricated using wet-jet phase inversion technique and the polymeric matrices used for the fabrication are polyvinylidine fluoride (PVDF) and polyvinyl chloride (PVC). Commercial hollow fiber membrane materials are made of polytetrafluoroethylene (PTFE) and polypropylene (PP). PVDF hollow fibers showed a superior performance among all the hollow fibers tested in the DCMD process and gave a water vapor flux of 31 kg m-2h-1 at a feed and coolant inlet temperatures of 80 and 20°C, respectively. Under the same conditions, the water vapor flux observed for PP, PTFE, and PVC hollow fiber membranes are 13, 11, and 6 kg m-2h-1, respectively, with 99.99% salt rejection observed for all membranes used.

  18. Methodology for construction of hollow spheres for use in physical phantoms

    International Nuclear Information System (INIS)

    Oliveira, A.C.H.; Lima, F.R.A.; Oliveira, F.; Vieira, J.W.

    2015-01-01

    In positron emission tomography (PET), quantitative evaluation of spatial resolution/object size, attenuation and scatter effects is often performed using phantoms with hollow spheres. Fillable, plastic-walled spheres are commercially available in several sizes. Radioactive solutions in any concentration can be injected into the spheres. Hollow spheres have several desirable traits, including repeatable, consistent use, and standardization across measurements at different institutions, since identical items are distributed by a single manufacturer. The objective of this work is to describe a methodology for construction of hollow spheres using rapid prototyping. It was used the software SolidWork (2014) to create five 3D models of the hollow spheres with inner diameters of 10 mm, 13 mm, 17 mm, 22 mm, and 28 mm. These models were based on hollow spheres of NEMA/IEC PET body phantom. It was used a Cubex Duo 3D printer (3D Systems) to build the hollow spheres. The material used was the ABS (acrylonitrile butadiene styrene) resin. (authors)

  19. Electro-magnetic properties of composites with aligned Fe-Co hollow fibers

    Directory of Open Access Journals (Sweden)

    Seungchan Cho

    2016-05-01

    Full Text Available A novel Fe-Co binary hollow fiber was synthesized by electroless plating using hydrolyzed polyester fiber and its anisotropy characteristic was investigated for electromagnetic wave absorbing materials. The hollow fibers in parallel with magnetic field show higher saturated magnetization of 202 emu/g at the applied magnetic field of 10 kOe and lower coercivity (27.658 Oe, compared with the random and vertical oriented hollow fibers. From complex permittivity measurement, the Fe-Co hollow fiber composites clearly display a single dielectric resonance, located at ∼14 GHz. The Fe-Co hollow fibers not only provide excellent EM properties in GHz frequency ranges, resulting mainly from the strong resonance, but also adjust the soft magnetic properties through fiber alignments. The cavitary structure of the Fe-Co hollow fibers, not only giving rise to a dielectric loss resonance and also adjusting its peak frequency, may be a pathway to useful EM wave absorptive devices in GHz frequency ranges.

  20. Adsorption characteristics of activated carbon hollow fibers

    Directory of Open Access Journals (Sweden)

    B. V. Kaludjerović

    2009-01-01

    Full Text Available Carbon hollow fibers were prepared with regenerated cellulose or polysulfone hollow fibers by chemical activation using sodium phosphate dibasic followed by the carbonization process. The activation process increases the adsorption properties of fibers which is more prominent for active carbone fibers obtained from the cellulose precursor. Chemical activation with sodium phosphate dibasic produces an active carbon material with both mesopores and micropores.

  1. Manufacturing hollow obturator with resilient denture liner on post hemimaxillectomy

    Directory of Open Access Journals (Sweden)

    Michael Josef Kridanto Kamadjaja

    2006-03-01

    Full Text Available A resilient denture liner is placed in the part of the hollow obturator base that contacts to post hemimaxillectomy mucosa. Replacing the resilient denture liner can makes the hollow obturator has an intimate contact with the mucosa, so it can prevents the mouth liquid enter to the cavum nasi and sinus, also eliminates painful because of using the hollow obturator. Resilient denture liner is a soft and resilient material that applied to the fitting surface of a denture in order to allow a more distribution of load. A case was reported about using the hollow obturator with resilient denture liner on post hemimaxillectomy to overcome these problems.

  2. Hollow fiber membranes and methods for forming same

    Science.gov (United States)

    Bhandari, Dhaval Ajit; McCloskey, Patrick Joseph; Howson, Paul Edward; Narang, Kristi Jean; Koros, William

    2016-03-22

    The invention provides improved hollow fiber membranes having at least two layers, and methods for forming the same. The methods include co-extruding a first composition, a second composition, and a third composition to form a dual layer hollow fiber membrane. The first composition includes a glassy polymer; the second composition includes a polysiloxane; and the third composition includes a bore fluid. The dual layer hollow fiber membranes include a first layer and a second layer, the first layer being a porous layer which includes the glassy polymer of the first composition, and the second layer being a polysiloxane layer which includes the polysiloxane of the second composition.

  3. Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment.

    Science.gov (United States)

    Zhang, Yuqi; Liu, Qiongming; Yu, Jicheng; Yu, Shuangjiang; Wang, Jinqiang; Qiang, Li; Gu, Zhen

    2017-09-26

    Obesity is one of the most serious public health problems in the 21st century that may lead to many comorbidities such as type-2 diabetes, cardiovascular diseases, and cancer. Current treatments toward obesity including diet, physical exercise, pharmacological therapy, as well as surgeries are always associated with low effectiveness or undesired systematical side effects. In order to enhance treatment efficiency with minimized side effects, we developed a transcutaneous browning agent patch to locally induce adipose tissue transformation. This microneedle-based patch can effectively deliver browning agents to the subcutaneous adipocytes in a sustained manner and switch on the "browning" at the targeted region. It is demonstrated that this patch reduces treated fat pad size, increases whole body energy expenditure, and improves type-2 diabetes in vivo in a diet-induced obesity mouse model.

  4. Study of the hollow cathode plasma electron-gun

    International Nuclear Information System (INIS)

    Zhang Yonghui; Jiang Jinsheng; Chang Anbi

    2003-01-01

    For developing a novel high-current, long pulse width electron source, the theoretics and mechanism of the hollow cathode plasma electron-gun are analyzed in detail in this paper, the structure and the physical process of hollow cathode plasma electron-gun are also studied. This gun overcomes the limitations of most high-power microwave tubes, which employ either thermionic cathodes that produce low current-density beams because of the limitation of the space charge, or field-emission cathodes that offer high current density but provide only short pulse width because of plasma closure of the accelerating gap. In the theories studying on hollow cathode plasma electron-gun, the characteristic of the hollow-cathode discharge is introduced, the action during the forming of plasma of the stimulating electrode and the modulating anode are discussed, the movement of electrons and ions and the primary parameters are analyzed, and the formulas of the electric field, beam current density and the stabilization conditions of the beam current are also presented in this paper. The numerical simulation is carried out based on Poisson's equation, and the equations of current continuity and movement. And the optimized result is reported. On this basis, we have designed a hollow-cathode-plasma electron-gun, whose output pulse current is 2 kA, and pulse width is 1 microsecond

  5. Fe2O3 hollow sphere nanocomposites for supercapacitor applications

    Science.gov (United States)

    Zhao, Yu; Wen, Yang; Xu, Bing; Lu, Lu; Ren, Reiming

    2018-02-01

    Nanomaterials have attracted increasing interest in electrochemical energy storage and conversion. Hollow sphere Fe2O3 nanocomposites were successfully prepared through facile low temperature water-bath method with carbon sphere as hard template. The morphology and microstructure of samples were characterized by X-ray diffraction (XRD) and Scanning electron microscope (SEM), respectively. Through hydrolysis mechanism, using ferric chloride direct hydrolysis, iron hydroxide coated on the surface of carbon sphere, after high temperature calcination can form the hollow spherical iron oxide materials. Electrochemical performances of the hollow sphere Fe2O3 nanocomposites electrodes were investigated by cyclic voltammery (CV) and galvanostatic charge/discharge. The Pure hollow sphere Fe2O3 nanocomposites achieves a specific capacitance of 125 F g-1 at the current density of 85 mA g-1. The results indicate that the uniform dispersion of hollow ball structure can effectively reduce the particle reunion in the process of charging and discharging.

  6. Energy-dependent expansion of .177 caliber hollow-point air gun projectiles.

    Science.gov (United States)

    Werner, Ronald; Schultz, Benno; Bockholdt, Britta; Ekkernkamp, Axel; Frank, Matthias

    2017-05-01

    Amongst hundreds of different projectiles for air guns available on the market, hollow-point air gun pellets are of special interest. These pellets are characterized by a tip or a hollowed-out shape in their tip which, when fired, makes the projectiles expand to an increased diameter upon entering the target medium. This results in an increase in release of energy which, in turn, has the potential to cause more serious injuries than non-hollow-point projectiles. To the best of the authors' knowledge, reliable data on the terminal ballistic features of hollow-point air gun projectiles compared to standard diabolo pellets have not yet been published in the forensic literature. The terminal ballistic performance (energy-dependent expansion and penetration) of four different types of .177 caliber hollow-point pellets discharged at kinetic energy levels from approximately 3 J up to 30 J into water, ordnance gelatin, and ordnance gelatin covered with natural chamois as a skin simulant was the subject of this investigation. Energy-dependent expansion of the tested hollow-point pellets was observed after being shot into all investigated target media. While some hollow-point pellets require a minimum kinetic energy of approximately 10 J for sufficient expansion, there are also hollow-point pellets which expand at kinetic energy levels of less than 5 J. The ratio of expansion (RE, calculated by the cross-sectional area (A) after impact divided by the cross-sectional area (A 0 ) of the undeformed pellet) of hollow-point air gun pellets reached values up of to 2.2. The extent of expansion relates to the kinetic energy of the projectile with a peak for pellet expansion at the 15 to 20 J range. To conclude, this work demonstrates that the hollow-point principle, i.e., the design-related enlargement of the projectiles' frontal area upon impact into a medium, does work in air guns as claimed by the manufacturers.

  7. Recovery of uranium from seawater using amidoxime hollow fibers

    International Nuclear Information System (INIS)

    Saito, K.; Uezu, K.; Hori, T.; Furusaki, S.; Sugo, T.; Okamoto, J.

    1988-01-01

    A novel amidoxime-group-containing adsorbent of hollow-fiber form (AO-H fiber) was prepared by radiation-induced graft polymerization of acrylonitrile onto a polyethylene hollow fiber, followed by chemical conversion of the produced cyano group to an amidoxime group. Distribution of the amidoxime group was uniform throughout hollow-fiber membrane. The fixed-bed adsorption column, 30 cm in length and charged with the bundle of AO-H fibers, was found to adsorb uranium from natural seawater at a sufficiently high rate: 0.66 mg uranium per g of adsorbent in 25 days

  8. A hollow definitive obturator fabrication technique for management of partial maxillectomy.

    Science.gov (United States)

    Patil, Pravinkumar Gajanan; Patil, Smita Pravinkumar

    2012-11-01

    Maxillary obturator prosthesis is the most frequent treatment option for management of partial or total maxillectomy. Heavy weight of the obturators is often a dislocating factor. Hollowing the prosthesis to reduce its weight is the well established fact. The alternate technique to hollow-out the prosthesis has been described in this article which is a variation of previously described processing techniques. A pre-shaped wax-bolus was incorporated inside the flasks during packing of the heat-polymerized acrylic resin to automatically create the hollow space. The processing technique described is a single step flasking procedure to construct a closed-hollow-obturator prosthesis as a single unit. To best understand the technique, this article describes management of a patient who had undergone partial maxillectomy secondary to squamous cell carcinoma rehabilitated with a hollow-obturator prosthesis.

  9. Preparation and surface encapsulation of hollow TiO nanoparticles for electrophoretic displays

    International Nuclear Information System (INIS)

    Zhao Qian; Tan Tingfeng; Qi Peng; Wang Shirong; Bian Shuguang; Li Xianggao; An Yong; Liu Zhaojun

    2011-01-01

    Hollow black TiO nanosparticles were obtained via deposition of inorganic coating on the surface of hollow core-shell polymer latex with Ti(OBu) 4 as precursor and subsequent calcination in ammonia gas. Hollow TiO particles were characterized by scanning electron microscope, transmission electronic microscopy, X-ray diffraction, and thermogravimetric analysis. Encapsulation of TiO via dispersion polymerization was promoved by pretreating the pigments with 3-(trimethoxysilyl) propyl methacrylate, making it possible to prepare hollow TiO-polymer particles. When St and DVB were used as polymerization monomer, hollow TiO-polymer core-shell particles came into being via dispersion polymerization, and the lipophilic degree is 28.57%. Glutin-arabic gum microcapsules containing TiO-polymer particles electrophoretic liquid were prepared using via complex coacervation. It was founded that hollow TiO-polymer particles had enough electrophoretic mobility after coating with polymer.

  10. Hollow Nanospheres Array Fabrication via Nano-Conglutination Technology.

    Science.gov (United States)

    Zhang, Man; Deng, Qiling; Xia, Liangping; Shi, Lifang; Cao, Axiu; Pang, Hui; Hu, Song

    2015-09-01

    Hollow nanospheres array is a special nanostructure with great applications in photonics, electronics and biochemistry. The nanofabrication technique with high resolution is crucial to nanosciences and nano-technology. This paper presents a novel nonconventional nano-conglutination technology combining polystyrenes spheres (PSs) self-assembly, conglutination and a lift-off process to fabricate the hollow nanospheres array with nanoholes. A self-assembly monolayer of PSs was stuck off from the quartz wafer by the thiol-ene adhesive material, and then the PSs was removed via a lift-off process and the hollow nanospheres embedded into the thiol-ene substrate was obtained. Thiolene polymer is a UV-curable material via "click chemistry" reaction at ambient conditions without the oxygen inhibition, which has excellent chemical and physical properties to be attractive as the adhesive material in nano-conglutination technology. Using the technique, a hollow nanospheres array with the nanoholes at the diameter of 200 nm embedded into the rigid thiol-ene substrate was fabricated, which has great potential to serve as a reaction container, catalyst and surface enhanced Raman scattering substrate.

  11. Biotemplate synthesis of monodispersed iron phosphate hollow microspheres

    International Nuclear Information System (INIS)

    Cao Feng; Li Dongxu

    2010-01-01

    Monodispersed iron phosphate hollow microspheres with a high degree of crystallization were prepared through a facile in situ deposition method using rape pollen grains as a biotemplate. The functional group on the surface of the pollen grains could adsorb Fe 3+ , which provided the nucleation sites for growth of iron phosphate nanoparticles. After being sintered at 600 deg. C for 10 h, the pollen grains were removed and iron phosphate hollow microspheres were obtained. A scanning electron microscope and x-ray diffraction were applied to characterize the morphology and crystalline structure of the pollen grains, iron phosphate-coated pollen grains and iron phosphate hollow microspheres. Differential scanning calorimetry and thermogravity analyses were performed to investigate the thermal behavior of the iron phosphate-coated pollen grains during the calcinations. Energy dispersive spectroscopy and Fourier transform infrared spectroscopy were utilized to investigate the interaction between the pollen grains and iron phosphate. The effect of the pollen wall on the surface morphology of these iron phosphate hollow microspheres was also proven in this work.

  12. Biotemplate synthesis of monodispersed iron phosphate hollow microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Cao Feng; Li Dongxu, E-mail: dongxuli@njut.edu.c [College of Materials Science and Engineering, Nanjing University of Technology, Jiangsu Nanjing 210009 (China)

    2010-03-15

    Monodispersed iron phosphate hollow microspheres with a high degree of crystallization were prepared through a facile in situ deposition method using rape pollen grains as a biotemplate. The functional group on the surface of the pollen grains could adsorb Fe{sup 3+}, which provided the nucleation sites for growth of iron phosphate nanoparticles. After being sintered at 600 deg. C for 10 h, the pollen grains were removed and iron phosphate hollow microspheres were obtained. A scanning electron microscope and x-ray diffraction were applied to characterize the morphology and crystalline structure of the pollen grains, iron phosphate-coated pollen grains and iron phosphate hollow microspheres. Differential scanning calorimetry and thermogravity analyses were performed to investigate the thermal behavior of the iron phosphate-coated pollen grains during the calcinations. Energy dispersive spectroscopy and Fourier transform infrared spectroscopy were utilized to investigate the interaction between the pollen grains and iron phosphate. The effect of the pollen wall on the surface morphology of these iron phosphate hollow microspheres was also proven in this work.

  13. Application of a probabilistic model of rainfall-induced shallow landslides to complex hollows

    Directory of Open Access Journals (Sweden)

    A. Talebi

    2008-07-01

    Full Text Available Recently, D'Odorico and Fagherazzi (2003 proposed "A probabilistic model of rainfall-triggered shallow landslides in hollows" (Water Resour. Res., 39, 2003. Their model describes the long-term evolution of colluvial deposits through a probabilistic soil mass balance at a point. Further building blocks of the model are: an infinite-slope stability analysis; a steady-state kinematic wave model (KW of hollow groundwater hydrology; and a statistical model relating intensity, duration, and frequency of extreme precipitation. Here we extend the work of D'Odorico and Fagherazzi (2003 by incorporating a more realistic description of hollow hydrology (hillslope storage Boussinesq model, HSB such that this model can also be applied to more gentle slopes and hollows with different plan shapes. We show that results obtained using the KW and HSB models are significantly different as in the KW model the diffusion term is ignored. We generalize our results by examining the stability of several hollow types with different plan shapes (different convergence degree. For each hollow type, the minimum value of the landslide-triggering saturated depth corresponding to the triggering precipitation (critical recharge rate is computed for steep and gentle hollows. Long term analysis of shallow landslides by the presented model illustrates that all hollows show a quite different behavior from the stability view point. In hollows with more convergence, landslide occurrence is limited by the supply of deposits (supply limited regime or rainfall events (event limited regime while hollows with low convergence degree are unconditionally stable regardless of the soil thickness or rainfall intensity. Overall, our results show that in addition to the effect of slope angle, plan shape (convergence degree also controls the subsurface flow and this process affects the probability distribution of landslide occurrence in different hollows. Finally, we conclude that

  14. Fire resistance of extruded hollow-core slabs

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl; Sørensen, Lars Schiøtt; Giuliani, Luisa

    2017-01-01

    to the structural codes with data derived from a standard fire test and from a thorough examination of the comprehensive test documentation available on fire exposed hollow-core slabs. Findings – Mechanisms for loss of load-bearing capacity are clarified, and evidence of the fire resistance is found. Originality......Purpose – Prefabricated extruded hollow-core slabs are preferred building components for floor structures in several countries. It is therefore important to be able to document the fire resistance of these slabs proving fulfilment of standard fire resistance requirements of 60 and 120 min found...... in most national building regulations. The paper aims to present a detailed analysis of the mechanisms responsible for the loss of loadbearing capacity of hollow-core slabs when exposed to fire. Design/methodology/approach – Furthermore, it compares theoretica calculation and assessment according...

  15. Method and apparatus for producing small hollow spheres

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1979-01-01

    A method and apparatus are described for producing small hollow spheres of glass, metal or plastic, wherein the sphere material is mixed with or contains as part of the composition a blowing agent which decomposes at high temperature (T greater than or equal to 600 0 C). As the temperature is quickly raised, the blowing agent decomposes and the resulting gas expands from within, thus forming a hollow sphere of controllable thickness. The thus produced hollow spheres (20 to 10 3 μm) have a variety of application, and are particularly useful in the fabrication of targets for laser implosion such as neutron sources, laser fusion physics studies, and laser initiated fusion power plants

  16. Mercury's Hollows: New Information on Distribution and Morphology from MESSENGER Observations at Low Altitude

    Science.gov (United States)

    Blewett, D. T.; Stadermann, A. C.; Chabot, N. L.; Denevi, B. W.; Ernst, C. M.; Peplowski, P. N.

    2014-12-01

    MESSENGER's orbital mission at Mercury led to the discovery of an unusual landform not known from other airless rocky bodies of the Solar System. Hollows are irregularly shaped, shallow, rimless depressions, often occurring in clusters and with high-reflectance interiors and halos. The fresh appearance of hollows suggests that they are relatively young features. For example, hollows are uncratered, and talus aprons downslope of hollows in certain cases appear to be covering small impact craters (100-200 in diameter). Hence, some hollows may be actively forming at present. The characteristics of hollows are suggestive of formation via destruction of a volatile-bearing phase (possibly one or more sulfides) through solar heating, micrometeoroid bombardment, and/or ion impact. Previous analysis showed that hollows are associated with low-reflectance material (LRM), a color unit identified from global color images. The material hosting hollows has often been excavated from depth by basin or crater impacts. Hollows are small features (tens of meters to several kilometers), so their detection and characterization with MESSENGER's global maps have been limited. MESSENGER's low-altitude orbits provide opportunities for collection of images at high spatial resolutions, which reveal new occurrences of hollows and offer views of hollows with unprecedented detail. As of this writing, we have examined more than 21,000 images with pixel sizes Shadow-length measurements were made on 280 images, yielding the depths of 1343 individual hollows. The mean depth is 30 m, with a standard deviation of 17 m. We also explored correlations between the geographic locations of hollows and maps provided by the MESSENGER geochemical sensors (X-Ray, Gamma-Ray, and Neutron Spectrometers), including the abundances of Al/Si, Ca/Si, Fe/Si, K, Mg/Si, and S/Si, as well as total neutron cross-section. No clear compositional trends emerged; it is likely that any true compositional preference for terrain

  17. Fundamental investigation on the impact strength of hollow fan blades

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, T; Miyachi, T; Sofue, Y

    1985-01-01

    Models of hollow fan blades were made and tested to prove that their strength is sufficient for use in real engines. The hollow blades were fabricated by diffusion bonding of two titanium alloy (6Al-4V-Ti) plates, one of which had three spanwise stiffners and the other being flat plate. The model as a nontwisted tapered blade. Impact tests were carried out on the hollow fan blade models in which the ingestion of a 1.5 pounds bird was simulated. Solid blades with the same external form were also tested by similar methods for comparison. The results of these tests show that properly designed hollow blades have sufficient stiffness and strength for use as fan blades in the turbo-fan engine.

  18. Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection.

    Science.gov (United States)

    Chiang, Bryce; Wang, Ke; Ethier, C Ross; Prausnitz, Mark R

    2017-01-01

    To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were acquired to determine clearance rates of molecules ranging in size from 332 Da to 2 MDa. Microneedle injections of fluorescein were performed, and samples were taken from various sites over time to determine amount of fluorescein exiting the eye. Clearance transport was modeled theoretically and compared with experimental data. After injection, pressures in SCS and vitreous humor spiked and returned to baseline within 20 minutes; there was no difference between these two pressures. Suprachoroidal space collapse occurred within 40 minutes. One hour after fluorescein injection, 46% of fluorescein was still present in the eye, 15% had transported across sclera, 6% had been cleared by choroidal vasculature, and 4% had exited via leakage pathways. Characteristic clearance time increased in proportion with molecular radius, but total clearance of 2 MDa FITC-dextran was significantly slower (21 days) than smaller molecules. These data generally agreed with predictions from a theoretical model of molecular transport. Guided by experimental data in the context of model predictions, molecular clearance from SCS occurred in three regimes: (1) on a time scale of approximately 10 minutes, fluid and molecules exited SCS by diffusion into sclera and choroid, and by pressure-driven reflux via transscleral leakage sites; (2) in approximately 1 hour, molecules cleared from choroid by blood flow; and (3) in 1 to 10 hours, molecules cleared from sclera by diffusion and convection.

  19. The Nature of Mercury's Hollows, and Space Weathering Close to the Sun

    Science.gov (United States)

    Blewett, D. T.; Chabot, N. L.; Denevi, B. W.; Ernst, C. M.

    2018-05-01

    Hollows are a landform that appear to form by loss of a volatile-bearing phase from silicate rock. Hollows are very young and are likely to be forming in the present day. Hollows may be an analog for extreme weathering on near-Sun asteroids.

  20. Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays.

    Science.gov (United States)

    Zaric, Marija; Becker, Pablo Daniel; Hervouet, Catherine; Kalcheva, Petya; Ibarzo Yus, Barbara; Cocita, Clement; O'Neill, Lauren Alexandra; Kwon, Sung-Yun; Klavinskis, Linda Sylvia

    2017-12-28

    The generation of tissue resident memory (T RM ) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the generation of long-lived antigen-specific CD8 + T cells that accumulate in mucosal tissues, including the female genital and respiratory tract. The memory CD8 + T cell population maintained in the peripheral mucosal tissues was attributable to a MA delivered AdHu5 vaccine instructing CD8 + T cell expression of CXCR3 + , CD103 +, CD49a + , CD69 + , CD127 + homing, retention and survival markers. Furthermore, memory CD8 + T cells generated by MA immunization significantly expanded upon locally administered antigenic challenge and showed a predominant poly-functional profile producing high levels of IFNγ and Granzyme B. These data demonstrate that skin vaccine delivery using microneedle technology induces mobilization of long lived, poly-functional CD8 + T cells to peripheral tissues, phenotypically displaying hallmarks of residency and yields new insights into how to design and deliver effective vaccine candidates with properties to exert local immunosurveillance at the mucosal surfaces. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Generation and propagation characteristics of a localized hollow beam

    Science.gov (United States)

    Xia, Meng; Wang, Zhizhang; Yin, Yaling; Zhou, Qi; Xia, Yong; Yin, Jianping

    2018-05-01

    A succinct experimental scheme is demonstrated to generate a localized hollow beam by using a π-phase binary bitmap and a convergent thin lens. The experimental results show that the aspect ratio of the dark-spot size of the hollow beam can be effectively controlled by the focal length of the lens. The measured beam profiles in free space also agree with the theoretical modeling. The studies hold great promise that such a hollow beam can be used to cool trapped atoms (or molecules) by Sisyphus cooling and to achieve an optically-trapped Bose–Einstein condensate by optical-potential evaporative cooling.

  2. Hydroxyapatite nanorod-assembled porous hollow polyhedra as drug/protein carriers.

    Science.gov (United States)

    Yu, Ya-Dong; Zhu, Ying-Jie; Qi, Chao; Jiang, Ying-Ying; Li, Heng; Wu, Jin

    2017-06-15

    Hydroxyapatite (HAP) with a porous hollow structure is an ideal biomaterial owing to its excellent biocompatibility and unique architecture. In this study, HAP nanorod-assembled porous hollow polyhedra, consisting of nanorod building blocks, have been successfully prepared at room temperature or under hydrothermal circumstances using a self-sacrificing Ca(OH) 2 template strategy. The hydrothermal treatment (at 180°C for 1h) can promote the HAP nanorods to be arranged with their axial direction normal to the polyhedron surface. The HAP nanorod-assembled porous hollow polyhedra have been explored for the potential application in drug/protein delivery, using ibuprofen (IBU) as a model drug and hemoglobin (Hb) as a model protein. The experimental results indicate that the HAP nanorod-assembled porous hollow polyhedra have a relatively high drug loading capacity and protein adsorption ability, and sustained drug and protein release. The HAP nanorod-assembled porous hollow polyhedra have promising applications in various biomedical fields such as the drug and protein delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. CAISSON TYPE HOLLOW FLOOR SLABS OF MONOLITHIC MULTI-STOREYED BUILDINGS

    Directory of Open Access Journals (Sweden)

    Malakhova Anna Nikolaevna

    2016-06-01

    Full Text Available One of the disadvantages of building structures made of reinforced concrete is their considerable weight. One of the trends to decrease the weight of concrete structures, including floor slabs, is the arrangement of voids in the cross-sectional building structures. In Russian and foreign practice paper, cardboard and plastic tubes has been used for creation of voids in the construction of monolithic floor slabs. Lightweight concretes were also used for production of precast hollow core floor slabs. The article provides constructive solutions of precast hollow core floor slabs and solid monolithic slabs that were used in the construction of buildings before wide use of large precast hollow core floor slabs. The article considers the application of caisson hollow core floor slabs for modern monolithic multi-storeyed buildings. The design solutions of such floor slabs, experimental investigations and computer modeling of their operation under load were described in this article. The comparative analysis of the calculation results of computer models of a hollow slabs formed of rod or plastic elements showed the similarity of calculation results.

  4. The crazy hollow formation (Eocene) of central Utah

    Science.gov (United States)

    Weiss, M.P.; Warner, K.N.

    2001-01-01

    The Late Eocene Crazy Hollow Formation is a fluviatile and lacustrine unit that was deposited locally in the southwest arm of Lake Uinta during and after the last stages of the lake the deposited the Green River Formation. Most exposures of the Crazy Hollow are located in Sanpete and Sevier Counties. The unit is characterized by a large variety of rock types, rapid facies changes within fairly short distances, and different lithofacies in the several areas where outcrops of the remnants of the formation are concentrated. Mudstone is dominant, volumetrically, but siltstone, shale, sandstone, conglomerate and several varieties of limestone are also present. The fine-grained rocks are mostly highly colored, especially in shades of yellow, orange and red. Sand grains, pebbles and small cobbles of well-rounded black chert are widespread, and "salt-and-pepper sandstone" is the conspicuous characteristic of the Crazy Hollow. The salt-and-pepper sandstone consists of grains of black chert, white chert, quartz and minor feldspar. The limestone beds and lenses are paludal and lacustrine in origin; some are fossiliferous, and contain the same fauna found in the Green River Formation. With trivial exceptions, the Crazy Hollow Formation lies on the upper, limestone member of the Green River Formation, and the beds of the two units are always accordant in attitude. The nature of the contact differs locally: at some sites there is gradation from the Green River to the Crazy Hollow; at others, rocks typical of the two units intertongue; elsewhere there is a disconformity between the two. A variety of bedrock units overlie the Crazy Hollow at different sites. In the southeasternmost districts it is overlain by the late Eocene formation of Aurora; in western Sevier County it is overlain by the Miocene-Pliocene Sevier River Formation; in northernmost Sanpete County it is overlain by the Oligocene volcanics of the Moroni Formation. At many sites bordering Sanpete and Sevier Valleys

  5. Hippocampal Neurogenesis and the Brain Repair Response to Brief Stereotaxic Insertion of a Microneedle

    Directory of Open Access Journals (Sweden)

    Shijie Song

    2013-01-01

    Full Text Available We tested the hypothesis that transient microinjury to the brain elicits cellular and humoral responses that stimulate hippocampal neurogenesis. Brief stereotaxic insertion and removal of a microneedle into the right hippocampus resulted in (a significantly increased expression of granulocyte-colony stimulating factor (G-CSF, the chemokine MIP-1a, and the proinflammatory cytokine IL12p40; (b pronounced activation of microglia and astrocytes; and (c increase in hippocampal neurogenesis. This study describes immediate and early humoral and cellular mechanisms of the brain’s response to microinjury that will be useful for the investigation of potential neuroprotective and deleterious effects of deep brain stimulation in various neuropsychiatric disorders.

  6. Research and application of active hollow core slabs in building systems for utilizing low energy sources

    International Nuclear Information System (INIS)

    Xu, Xinhua; Yu, Jinghua; Wang, Shengwei; Wang, Jinbo

    2014-01-01

    Highlights: • A review on the development and modeling of active hollow core slab is presented. • The applications and performance evaluation of the slab in building are reviewed. • Finite element or finite difference method is often used in multidimensional model. • Performance evaluations of building using active slabs for ventilation are limited. • More works on the active hollow core slab are worthwhile. - Abstract: The society and the building professionals have paid much concern in recent years on building energy efficiency and the development and applications of low energy technologies for buildings/green buildings allowing the elimination, or at least reduction of dependence on electricity or fossil fuel while maintaining acceptable indoor environment. Utilizations of favorable diurnal temperature difference and ground thermal source for air conditioning are among these low energy technologies. Utilization of the hollow cores in the prefabricated slab for ventilation and the mass of the slab for thermal storage is widely used in building systems in Europe by exploiting the low energy source of the ambient air. These hollow core slabs aim at enlarging the heat transfer surface between the slab mass and the air in the core, which permits substantial heat flows even for relatively small temperature differences. This, in turn, allows the use of low energy cooling or heating sources, such as the ground, outside air or recovered process heat. In this paper, we present a comprehensive review of the research and application of active hollow core slabs in building systems for utilizing low energy sources. The principle and development of active hollow core slabs in building systems for leveling the indoor temperature fluctuation by ventilation air passing the cores are described. Calculation models of the active hollow core concrete slab as well as the practical applications and performance evaluation of the slab applied in building systems for air

  7. Structural investigation of spherical hollow excipient Mannit Q by X-ray microtomography.

    Science.gov (United States)

    Kajihara, Ryusuke; Noguchi, Shuji; Iwao, Yasunori; Yasuda, Yuki; Segawa, Megumi; Itai, Shigeru

    2015-11-10

    The structure of Mannit Q particles, an excipient made by spray-drying a d-mannitol solution, and Mannit Q tablets were investigated by synchrotron X-ray microtomography. The Mannit Q particles had a spherical shape with a hollow core. The shells of the particles consisted of fine needle-shaped crystals, and columnar crystals were present in the hollows. These structural features suggested the following formation mechanism for the hollow particles:during the spray-drying process, the solvent rapidly evaporated from the droplet surface, resulting in the formation of shells made of fine needle-shaped crystals.Solvent remaining inside the shells then evaporated slowly and larger columnar crystals grew as the hollows formed. Although most of the Mannit Q particles were crushed on tableting, some of the particles retained their hollow structures, probably because the columnar crystals inside the hollows functioned as props. This demonstrated that the tablets with porous void spaces may be readily manufactured using Mannit Q. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Emission mechanism in high current hollow cathode arcs

    International Nuclear Information System (INIS)

    Krishnan, M.

    1976-01-01

    Large (2 cm-diameter) hollow cathodes have been operated in a magnetoplasmadynamic (MPD) arc over wide ranges of current (0.25 to 17 kA) and mass flow (10 -3 to 8 g/sec), with orifice current densities and mass fluxes encompassing those encountered in low current steady-state hollow cathode arcs. Detailed cathode interior measurements of current and potential distributions show that maximum current penetration into the cathode is about one diameter axially upstream from the tip, with peak inner surface current attachment up to one cathode diameter upstream of the tip. The spontaneous attachment of peak current upstream of the cathode tip is suggested as a criterion for characteristic hollow cathode operation. This empirical criterion is verified by experiment

  9. Evolution of ESR Technology and Equipment for Long Hollow Ingots Manufacture

    Science.gov (United States)

    Medovar, Lev; Stovpchenko, Ganna; Dudka, Grigory; Kozminskiy, Alexander; Fedorovskii, Borys; Lebid, Vitalii; Gusiev, Iaroslav

    In this paper development of both ESR technology and equipment for hollow ingot manufacture review and analysis are presented. The real complications of hollow ingot manufacture and some tendentious issues which restrict process dissemination are discussed. An actual data of modern manufacture of as-cast pipes for heat and power engineering by traditional ESR with consumable electrode are given. Results of microstructure and nonmetal inclusion investigations have shown the high quality of as-cast ESR pipes. On the basis of these results the possibility to produce huge ESR hollows (up 5000 mm in dia) with final goal drastically to reduce setting ratio on forged shells and rings or even replace it by ESR hollows as-cast is grounded. Two new ESR technologies — consumable electrodes change and liquid metal usage — have passed pilot tests for heavy hollow production and shown very prospective results to be presented.

  10. Hollow-core photonic band gap fibers for particle acceleration

    Directory of Open Access Journals (Sweden)

    Robert J. Noble

    2011-12-01

    Full Text Available Photonic band gap (PBG dielectric fibers with hollow cores are being studied both theoretically and experimentally for use as laser driven accelerator structures. The hollow core functions as both a longitudinal waveguide for the transverse-magnetic (TM accelerating fields and a channel for the charged particles. The dielectric surrounding the core is permeated by a periodic array of smaller holes to confine the mode, forming a photonic crystal fiber in which modes exist in frequency passbands, separated by band gaps. The hollow core acts as a defect which breaks the crystal symmetry, and so-called defect, or trapped modes having frequencies in the band gap will only propagate near the defect. We describe the design of 2D hollow-core PBG fibers to support TM defect modes with high longitudinal fields and high characteristic impedance. Using as-built dimensions of industrially made fibers, we perform a simulation analysis of prototype PBG fibers with dimensions appropriate for speed-of-light TM modes.

  11. Method for selecting hollow microspheres for use in laser fusion targets

    Science.gov (United States)

    Farnum, Eugene H.; Fries, R. Jay; Havenhill, Jerry W.; Smith, Maurice Lee; Stoltz, Daniel L.

    1976-01-01

    Hollow microspheres having thin and very uniform wall thickness are useful as containers for the deuterium and tritium gas mixture used as a fuel in laser fusion targets. Hollow microspheres are commercially available; however, in commercial lots only a very small number meet the rigid requirements for use in laser fusion targets. Those meeting these requirements may be separated from the unsuitable ones by subjecting the commercial lot to size and density separations and then by subjecting those hollow microspheres thus separated to an external pressurization at which those which are aspherical or which have nonuniform walls are broken and separating the sound hollow microspheres from the broken ones.

  12. Curative effects of microneedle fractional radiofrequency system on skin laxity in Asian patients: A prospective, double-blind, randomized, controlled face-split study.

    Science.gov (United States)

    Lu, Wenli; Wu, Pinru; Zhang, Zhen; Chen, Jinan; Chen, Xiangdong; Ewelina, Biskup

    2017-04-01

    To date, no studies compared curative effects of thermal lesions in deep and superficial dermal layers in the same patient (face-split study). To evaluate skin laxity effects of microneedle fractional radiofrequency induced thermal lesions in different dermal layers. 13 patients underwent three sessions of a randomized face-split microneedle fractional radiofrequency system (MFRS) treatment of deep dermal and superficial dermal layer. Skin laxity changes were evaluated objectively (digital images, 2 independent experts) and subjectively (patients' satisfaction numerical rating). 12 of 13 subjects completed a course of 3 treatments and a 1-year follow-up. Improvement of nasolabial folds in deep dermal approach was significantly better than that in superficial approach at three months (P=.0002) and 12 months (P=.0057) follow-up. Effects on infraorbital rhytides were only slightly better (P=.3531). MFRS is an effective method to improve skin laxity. Thermal lesion approach seems to provide better outcomes when applied to deep dermal layers. It is necessary to consider the skin thickness of different facial regions when choosing the treatment depth.

  13. Periodic organosilica hollow nanospheres as anode materials for lithium ion rechargeable batteries

    Science.gov (United States)

    Sasidharan, Manickam; Nakashima, Kenichi; Gunawardhana, Nanda; Yokoi, Toshiyuki; Ito, Masanori; Inoue, Masamichi; Yusa, Shin-Ichi; Yoshio, Masaki; Tatsumi, Takashi

    2011-11-01

    Polymeric micelles with core-shell-corona architecture have been found to be the efficient colloidal templates for synthesis of periodic organosilica hollow nanospheres over a broad pH range from acidic to alkaline media. In alkaline medium, poly (styrene-b-[3-(methacryloylamino)propyl] trimethylammonium chloride-b-ethylene oxide) (PS-PMAPTAC-PEO) micelles yield benzene-silica hollow nanospheres with molecular scale periodicity of benzene groups in the shell domain of hollow particles. Whereas, an acidic medium (pH 4) produces diverse hollow particles with benzene, ethylene, and a mixture of ethylene and dipropyldisulfide bridging functionalities using poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) micelles. These hollow particles were thoroughly characterized by powder X-ray diffraction (XRD), dynamic light scattering (DLS), thermogravimetric analysis (TG/DTA), Fourier transformation infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), magic angle spinning-nuclear magnetic resonance (29Si MAS NMR and 13CP-MAS NMR), Raman spectroscopy, and nitrogen adsorption/desorption analyses. The benzene-silica hollow nanospheres with molecular scale periodicity in the shell domain exhibit higher cycling performance of up to 300 cycles in lithium ion rechargeable batteries compared with micron-sized dense benzene-silica particles.Polymeric micelles with core-shell-corona architecture have been found to be the efficient colloidal templates for synthesis of periodic organosilica hollow nanospheres over a broad pH range from acidic to alkaline media. In alkaline medium, poly (styrene-b-[3-(methacryloylamino)propyl] trimethylammonium chloride-b-ethylene oxide) (PS-PMAPTAC-PEO) micelles yield benzene-silica hollow nanospheres with molecular scale periodicity of benzene groups in the shell domain of hollow particles. Whereas, an acidic medium (pH 4) produces diverse hollow particles with benzene, ethylene, and a mixture of ethylene and

  14. Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin.

    Science.gov (United States)

    Prausnitz, Mark R

    2017-06-07

    Microneedle patches (MNPs) contain arrays of solid needles measuring hundreds of microns in length that deliver drugs and vaccines into skin in a painless, easy-to-use manner. Optimal MNP design balances multiple interdependent parameters that determine mechanical strength, skin-insertion reliability, drug delivery efficiency, painlessness, manufacturability, and other features of MNPs that affect their performance. MNPs can be made by adapting various microfabrication technologies for delivery of small-molecule drugs, biologics, and vaccines targeted to the skin, which can have pharmacokinetic and immunologic advantages. A small number of human clinical trials, as well as a large and growing market for MNP products for cosmetics, indicate that MNPs can be used safely, efficaciously, and with strong patient acceptance. More advanced clinical trials and commercial-scale manufacturing will facilitate development of MNPs to realize their potential to dramatically increase patient access to otherwise-injectable drugs and to improve drug performance via skin delivery.

  15. Bubble template synthesis of hollow gold nanoparticles and their applications as theranostic agents

    Science.gov (United States)

    Huang, Chienwen

    Hollow gold nanoparticle with a sub-30nm polycrystalline shell and a 50 nm hollow core has been successfully synthesized through the reduction of sodium gold sulfite by electrochemically evolved hydrogen. Such hollow gold nanoparticles exhibit unique plasmonic properties. They strongly scatter and absorb near infrared light. In this thesis we seek to understand the formation mechanism of hollow gold nanoparticles in this new synthesis process and their plasmonic properties. Also, we explore their biomedical applications as theranostic agents (therapeutic and diagnostic imaging). A lithographically patterned electrode consisting of Ag stripes on a glass substrate was used to investigate the formation process of hollow gold nanoparticles. Ag stripes served as working electrode for electrochemically evolution of hydrogen, and adjacent glass areas provided supporting surface for hydrogen nanobubbles nucleation and growth. Hydrogen nanobubbles served as both templates and reducing agents to trigger the autocatalytic disproportionation reaction of sodium gold sulfite. The effects of applied potential and the additives in the electrolyte have been studied. It has been found that the size and size distribution of hollow gold nanoparticle are directly relative to the applied potential, i.e. the hydrogen evolution rate. It has also been found the addition of Ni2+ ions can greatly improve the size distribution of hollow gold nanoparticles that can be contributed to that the newly electrodeposited nickel metal can enhance the hydrogen evolution efficiency. Another additive, ethylenediamine (EDA) can suppress the autocatalytic reaction of gold sulfite to increase the stability of sodium gold sulfite electrolyte. To capture such electrochemically evolved hydrogen nanobubbles, and subsequently to generate hollow gold nanoparticles in large numbers, alumina membranes were placed on the top of the working electrode. Anodic alumina membrane consists of ~200 nm pores, which provides

  16. Electromagnetic wave absorption properties of composites with ultrafine hollow magnetic fibers

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Jin Woo [Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (BK21 Granted Program), 291 Daehak-ro, Yuseong-gu, Daejeon (Korea, Republic of); Composites Research Center, Korea Institute of Materials Science, 66 Sang-nam-dong, Changwon, Gyeongnam (Korea, Republic of); Lee, Sang Bok; Kim, Jin Bong; Lee, Sang Kwan [Composites Research Center, Korea Institute of Materials Science, 66 Sang-nam-dong, Changwon, Gyeongnam (Korea, Republic of); Park, O Ok, E-mail: oopark@kaist.ac.kr [Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (BK21 Granted Program), 291 Daehak-ro, Yuseong-gu, Daejeon (Korea, Republic of); Department of Energy Systems Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), 50-1, Sang-ri, Hyeongpung-myeon, Dalseong-gun, Daegu 711-873 (Korea, Republic of)

    2014-06-01

    Ultrafine hollow magnetic fibers were prepared by electroless plating using hydrolyzed polyester fiber as a sacrificial substrate. These hollow fibers can be served for lightweight and efficient electromagnetic (EM) absorbing materials. As observed from SEM and EDS analysis, hollow structures consisting of Ni inner layer and Fe or Fe–Co outer layer were obtained. By introducing Co onto Fe, oxidation of the Fe layer was successfully prevented making it possible to enhance the complex permeability compared to a case in which only Fe was used. Polymeric composites containing the hollow fibers with different weight fractions and fiber lengths were prepared by a simple mixing process. The electromagnetic wave properties of the composites were measured by a vector network analyzer and it was found that the hollow magnetic fibers show a clear resonance peak of the complex permittivity around the X-band range (8–12 GHz) and the resonance frequency strongly depends on the fiber concentration and length. A possible explanation for the unique resonance is that the hollow fibers possess relatively low electrical conductivity and a long mean free path due to their oxidized phase and hollow structure. The calculated EM wave absorption with the measured EM wave properties showed that the composite containing 30 wt% hollow Ni/Fe–Co (7:3) fibers in length of 180 μm exhibited multiple absorbance peaks resulting in a broad absorption bandwidth of 4.2 GHz. It is obvious that this multiple absorbance is attributed to the resonance characteristic of the composite. - Highlights: • The ultrafine hollow fibers consist of inner Ni layer (∼100 nm) and outer Fe or Fe–Co layer (500–700 nm). • Composites with the fibers show a high permittivity as well as permeability at low weight fractions (10–30 wt%). • The composites show a permittivity resonance and the resonance frequency can be controlled by fiber content and length. • The composite absorber exhibits a double

  17. Porous-wall hollow glass microspheres as carriers for biomolecules

    Science.gov (United States)

    Li, Shuyi; Dynan, William S; Wicks, George; Serkiz, Steven

    2013-09-17

    The present invention includes compositions of porous-wall hollow glass microspheres and one or more biomolecules, wherein the one or more biomolecules are positioned within a void location within the hollow glass microsphere, and the use of such compositions for the diagnostic and/or therapeutic delivery of biomolecules.

  18. Hollow fiber apparatus and use thereof for fluids separations and heat and mass transfers

    Energy Technology Data Exchange (ETDEWEB)

    Bikson, Benjamin; Etter, Stephen; Ching, Nathaniel

    2017-04-18

    A hollow fiber fluid separation device includes a hollow fiber cartridge, comprising a plurality of hollow fiber membranes arranged around a central tubular core, a first tubesheet and a second tubesheet encapsulating respective distal ends of the hollow fiber bundle. The tubesheets have boreholes in fluid communication with bores of the hollow fiber membrane. In at least one of the tubesheets, the boreholes are formed radially and are in communication with the central tubular core. The hollow fiber fluid separation device can be utilized in liquid separation applications such as ultrafiltration and in gas separation processes such as air separation. The design disclosed herein is light weight and compact and is particularly advantageous at high operating temperatures when the pressure of the feed fluid introduced into the bores of hollow fibers is higher than the pressure on the shell side of the device.

  19. Axisymmetric Vibration of Piezo-Lemv Composite Hollow Multilayer Cylinder

    Directory of Open Access Journals (Sweden)

    E. S. Nehru

    2012-01-01

    Full Text Available Axisymmetric vibration of an infinite piezolaminated multilayer hollow cylinder made of piezoelectric layers of 6 mm class and an isotropic LEMV (Linear Elastic Materials with Voids layers is studied. The frequency equations are obtained for the traction free outer surface with continuity conditions at the interfaces. Numerical results are carried out for the inner, middle, and outer hollow piezoelectric layers bonded by LEMV (It is hypothetical material layers and the dispersion curves are compared with that of a similar 3-layer model and of 3 and 5 layer models with inner, middle, and outer hollow piezoelectric layers bonded by CFRP (Carbon fiber reinforced plastics.

  20. Hollow Mill for Extraction of Stripped Titanium Screws: An Easy ...

    African Journals Online (AJOL)

    countries. The known alternative in such condition is ... Key words: Hollow mill, stripped screws, titanium locked plates ... used a locally manufactured stainless steel hollow mill, ... head ‑ plate hole” assembly as a mono‑block single unit. In.

  1. Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis

    Directory of Open Access Journals (Sweden)

    Gui Chen

    2015-11-01

    Full Text Available Triptolide (TP, a major active component of Tripterygium wilfordii Hook.F. (TWHF, is used to treat rheumatoid arthritis (RA. However, it has a narrow therapeutic window due to its serious toxicities. To increase the therapeutic index, a new triptolide-loaded transdermal delivery system, named triptolide-loaded liposome hydrogel patch (TP-LHP, has been developed. In this paper, we used a micro-needle array to deliver TP-LHP to promote transdermal absorption and evaluated this treatment on the pharmacokinetics and pharmacodynamics of TP-LHP in a rat model of collagen-induced arthritis (CIA. The pharmacokinetic results showed that transdermal delivery of microneedle TP-LHP yielded plasma drug levels which fit a one-compartment open model. The relationship equation between plasma concentration and time was C=303.59×(e−0.064t−e−0.287t. The results of pharmacodynamic study demonstrated that TP-LHP treatment mitigated the degree of joint swelling and suppressed the expressions of fetal liver kinase-1, fetal liver tyrosine kinase-4 and hypoxia-inducible factor-1α in synovium. Other indicators were also reduced by TP-LHP, including hyperfunction of immune, interleukin-1β and interleukin-6 levels in serum. The therapeutic mechanism of TP-LHP might be regulation of the balance between Th1 and Th2, as well as inhibition of the expression and biological effects of vascular endothelial growth factor.

  2. Polymer micromold and fabrication process

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Abraham P. (1428 Whitecliff Way, Walnut Creek, CA 94596); Northrup, M. Allen (923 Creston Rd., Berkeley, CA 94708); Ahre, Paul E. (1299 Gonzaga Ct., Livermore, CA 94550); Dupuy, Peter C. (1736 Waldo Ct., Modesto, CA 95358)

    1997-01-01

    A mold assembly with micro-sized features in which the hollow portion thereof is fabricated from a sacrificial mandrel which is surface treated and then coated to form an outer shell. The sacrificial mandrel is then selectively etched away leaving the outer shell as the final product. The sacrificial mandrel is fabricated by a precision lathe, for example, so that when removed by etching the inner or hollow area has diameters as small as 10's of micros (.mu.m). Varying the inside diameter contours of the mold can be accomplished with specified ramping slopes formed on the outer surface of the sacrificial mandrel, with the inside or hollow section being, for example, 275 .mu.m in length up to 150 .mu.m in diameter within a 6 mm outside diameter (o.d.) mold assembly. The mold assembly itself can serve as a micronozzle or microneedle, and plastic parts, such as microballoons for angioplasty, polymer microparts, and microactuators, etc., may be formed within the mold assembly.

  3. Evolution of radiation resistant hollow fibers membranes for nuclear

    International Nuclear Information System (INIS)

    Neelam Kumari; Raut, D.R.; Bhardwaj, Y.K.; Mohapatra, P.K.

    2014-01-01

    We have evaluated hollow fiber supported liquid membrane (HFSLM) technique for the separation of actinides, fission products and other valuables from the nuclear waste solutions. In this technique, ligand responsible for separation of metal ion is held in tiny pores of membrane. Any drastic change as a consequence of irradiation, like change in pore size, change in hydrophobicity of polymeric material can be fatal for separation process as it may lead dislodging of carrier ligands from the pores. It was therefore needed to study the irradiation stability of hollow fibers. We have earlier showed that polypropylene fibers were stable up to 500 radiation dose and we therefore need to look into other options. In the present work, hollow fiber membranes made from polyether ether ketone (PEEK), polysulphone (PS). Polymers were evaluated for their radiation stability after exposing to varying absorbed dose of gamma radiation. The hollow fibers were irradiated to 100 KGy, 200 KGy, 500 KGy and 1000 KGy and its changes in hydrophobicity were measured using contact angle measurement studies

  4. Polymer blends used to develop felodipine-loaded hollow microspheres for improved oral bioavailability.

    Science.gov (United States)

    Pi, Chao; Feng, Ting; Liang, Jing; Liu, Hao; Huang, Dongmei; Zhan, Chenglin; Yuan, Jiyuan; Lee, Robert J; Zhao, Ling; Wei, Yumeng

    2018-06-01

    Felodipine (FD) has been widely used in anti-hypertensive treatment. However, it has extremely low aqueous solubility and poor bioavailability. To address these problems, FD hollow microspheres as multiple-unit dosage forms were synthesized by a solvent diffusion evaporation method. Particle size of the hollow microspheres, types of ethylcellulose (EC), amounts of EC, polyvinyl pyrrolidone (PVP) and FD were investigated based on an orthogonal experiment of three factors and three levels. In addition, the release kinetics in vitro and pharmacokinetics in beagle dogs of the optimized FD hollow microspheres was investigated and compared with Plendil (commercial FD sustained-release tablets) as a single-unit dosage form. Results showed that the optimal formulation was composed of EC 10 cp :PVP:FD (0.9:0.16:0.36, w/w). The FD hollow microspheres were globular with a hollow structure and have high drug loading (17.69±0.44%) and floating rate (93.82±4.05%) in simulated human gastric fluid after 24h. Pharmacokinetic data showed that FD hollow microspheres exhibited sustained-release behavior and significantly improved relative bioavailability of FD compared with the control. Pharmacodynamic study showed that the FD hollow microspheres could effectively lower blood pressure. Therefore, these findings demonstrated that the hollow microspheres were an effective sustained-release delivery system for FD. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Method for sizing hollow microspheres

    Science.gov (United States)

    Farnum, E.H.; Fries, R.J.

    1975-10-29

    Hollow Microspheres may be effectively sized by placing them beneath a screen stack completely immersed in an ultrasonic bath containing a liquid having a density at which the microspheres float and ultrasonically agitating the bath.

  6. Pressure effects in hollow and solid iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Silva, N.J.O., E-mail: nunojoao@ua.pt [Departamento de Física and CICECO, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Saisho, S.; Mito, M. [Faculty of Engineering, Kyushu Institute of Technology, Kitakyushu 804-8550 (Japan); Millán, A.; Palacio, F. [Instituto de Ciencia de Materiales de Aragón, CSIC - Universidad de Zaragoza. Departamento de Física de la Materia Condensada, Facultad de Ciencias, 50009 Zaragoza (Spain); Cabot, A. [Universitat de Barcelona and Catalonia Energy Research Institute, Barcelona (Spain); Iglesias, Ò.; Labarta, A. [Departament de Física Fonamental, Universitat de Barcelona and Institut de Nanociència i Nanotecnologia, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona (Spain)

    2013-06-15

    We report a study on the pressure response of the anisotropy energy of hollow and solid maghemite nanoparticles. The differences between the maghemite samples are understood in terms of size, magnetic anisotropy and shape of the particles. In particular, the differences between hollow and solid samples are due to the different shape of the nanoparticles and by comparing both pressure responses it is possible to conclude that the shell has a larger pressure response when compared to the core. - Highlights: ► Study of the pressure response of core and shell magnetic anisotropy. ► Contrast between hollow and solid maghemite nanoparticles. ► Disentanglement of nanoparticles core and shell magnetic properties.

  7. Theoretical prediction of low-density hexagonal ZnO hollow structures

    Energy Technology Data Exchange (ETDEWEB)

    Tuoc, Vu Ngoc, E-mail: tuoc.vungoc@hust.edu.vn [Institute of Engineering Physics, Hanoi University of Science and Technology, 1 Dai Co Viet Road, Hanoi (Viet Nam); Huan, Tran Doan [Institute of Materials Science, University of Connecticut, Storrs, Connecticut 06269-3136 (United States); Thao, Nguyen Thi [Institute of Engineering Physics, Hanoi University of Science and Technology, 1 Dai Co Viet Road, Hanoi (Viet Nam); Hong Duc University, 307 Le Lai, Thanh Hoa City (Viet Nam); Tuan, Le Manh [Hong Duc University, 307 Le Lai, Thanh Hoa City (Viet Nam)

    2016-10-14

    Along with wurtzite and zinc blende, zinc oxide (ZnO) has been found in a large number of polymorphs with substantially different properties and, hence, applications. Therefore, predicting and synthesizing new classes of ZnO polymorphs are of great significance and have been gaining considerable interest. Herein, we perform a density functional theory based tight-binding study, predicting several new series of ZnO hollow structures using the bottom-up approach. The geometry of the building blocks allows for obtaining a variety of hexagonal, low-density nanoporous, and flexible ZnO hollow structures. Their stability is discussed by means of the free energy computed within the lattice-dynamics approach. Our calculations also indicate that all the reported hollow structures are wide band gap semiconductors in the same fashion with bulk ZnO. The electronic band structures of the ZnO hollow structures are finally examined in detail.

  8. Studies on pulsed hollow cathode capillary discharges

    Energy Technology Data Exchange (ETDEWEB)

    Choi, P; Dumitrescu-Zoita, C; Larour, J; Rous, J [Ecole Polytechnique, 91 - Palaiseau (France). Lab. de Physique des Milieux Ionises; Favre, M; Moreno, J; Chuaqui, H; Wyndham, E [Pontificia Univ. Catolica de Chile, Santiago (Chile). Facultad de Fisica; Zambra, M [Comision Chilena de Energia Nuclear, Santiago (Chile); Wong, C S [Univ. of Malaya, Kuala Lumpur (Malaysia). Plasma Research Lab

    1997-12-31

    Preliminary results on radiation characteristics of pulsed hollow cathode capillary discharges are presented. The device combines the on axis electron beam assisted ionization capabilities of the transient hollow cathode discharge with a novel high voltage low inductance geometrical design, which integrates the local energy storage into the electrode system. A nanosecond regime high temperature plasma is produced in a long, high aspect ratio capillary, with light emission in the UV to XUV region. The discharge is operated from near vacuum to pressure in the 1000 mTorr range. (author). 2 figs., 7 refs.

  9. Biomolecule-assisted construction of cadmium sulfide hollow spheres with structure-dependent photocatalytic activity.

    Science.gov (United States)

    Wei, Chengzhen; Zang, Wenzhe; Yin, Jingzhou; Lu, Qingyi; Chen, Qun; Liu, Rongmei; Gao, Feng

    2013-02-25

    In this study, we report the synthesis of monodispersive solid and hollow CdS spheres with structure-dependent photocatalytic abilities for dye photodegradation. The monodispersive CdS nanospheres were constructed with the assistance of the soulcarboxymthyi chitosan biopolymer under hydrothermal conditions. The solid CdS spheres were corroded by ammonia to form hollow CdS nanospheres through a dissolution-reprecipitation mechanism. Their visible-light photocatalytic activities were investigated, and the results show that both the solid and the hollow CdS spheres have visible-light photocatalytic abilities for the photodegradation of dyes. The photocatalytic properties of the CdS spheres were demonstrated to be structure dependent. Although the nanoparticles comprising the hollow spheres have larger sizes than those comprising the solid spheres, the hollow CdS spheres have better photocatalytic performances than the solid CdS spheres, which can be attributed to the special hollow structure. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Preparation of SnO 2 /Carbon Composite Hollow Spheres and Their Lithium Storage Properties

    KAUST Repository

    Lou, Xiong Wen; Deng, Da; Lee, Jim Yang; Archer, Lynden A.

    2008-01-01

    In this work, we present a novel concept of structural design for preparing functional composite hollow spheres and derived double-shelled hollow spheres. The approach involves two main steps: preparation of porous hollow spheres of one component and deposition of the other component onto both the interior and exterior surfaces of the shell as well as in the pores. We demonstrate the concept by preparing SnO2/carbon composite hollow spheres and evaluate them as potential anode materials for lithium-ion batteries. These SnO2/carbon hollow spheres are able to deliver a reversible Li storage capacity of 473 mA h g-1 after 50 cycles. Unusual double-shelled carbon hollow spheres are obtained by selective removal of the sandwiched porous SnO2 shells. © 2008 American Chemical Society.

  11. Preparation of SnO 2 /Carbon Composite Hollow Spheres and Their Lithium Storage Properties

    KAUST Repository

    Lou, Xiong Wen

    2008-10-28

    In this work, we present a novel concept of structural design for preparing functional composite hollow spheres and derived double-shelled hollow spheres. The approach involves two main steps: preparation of porous hollow spheres of one component and deposition of the other component onto both the interior and exterior surfaces of the shell as well as in the pores. We demonstrate the concept by preparing SnO2/carbon composite hollow spheres and evaluate them as potential anode materials for lithium-ion batteries. These SnO2/carbon hollow spheres are able to deliver a reversible Li storage capacity of 473 mA h g-1 after 50 cycles. Unusual double-shelled carbon hollow spheres are obtained by selective removal of the sandwiched porous SnO2 shells. © 2008 American Chemical Society.

  12. Size and thickness effect on magnetic structures of maghemite hollow magnetic nanoparticles

    International Nuclear Information System (INIS)

    Sayed, Fatima; Labaye, Yvan; Sayed Hassan, Rodaina; El Haj Hassan, Fouad; Yaacoub, Nader; Greneche, Jean-Marc

    2016-01-01

    The effect of surface anisotropy on the magnetic ground state of hollow maghemite nanoparticles is investigated using atomistic Monte Carlo simulation. The computer modeling is carried on hollow nanostructures as a function of size and shell thickness. It is found that the large contribution of the surface anisotropy imposes a “throttled” spin structure where the moments located at the outer surface tend to orient normal to the surface while those located at the inner surface appear to be more aligned. For increasing values of surface anisotropy in the frame of a radial model, the magnetic moments become radially oriented either inward or outward giving rise to a “hedgehog” configuration with nearly zero net magnetization. We also show the effect of the size of hollow nanoparticle on the spin behavior where the spin non-collinearity increases (for fixed value of surface anisotropy) as the diameter of the hollow nanoparticle increases due to the significant increase in surface-to-volume ratio, the thickness being constant. Moreover, the thickness of the hollow nanoparticle shell influences the spin configuration and thus the relation between surface anisotropy and the size or the thickness of the hollow nanoparticle is established.

  13. Size and thickness effect on magnetic structures of maghemite hollow magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Sayed, Fatima; Labaye, Yvan, E-mail: yvan.labaye@univ-lemans.fr [Université du Maine, Institut des Molécules et Matériaux du Mans CNRS UMR-6283 (France); Sayed Hassan, Rodaina; El Haj Hassan, Fouad [Université Libanaise, Faculté des Sciences Section I, MPLAB (Lebanon); Yaacoub, Nader, E-mail: nader.yaacoub@univ-lemans.fr; Greneche, Jean-Marc [Université du Maine, Institut des Molécules et Matériaux du Mans CNRS UMR-6283 (France)

    2016-09-15

    The effect of surface anisotropy on the magnetic ground state of hollow maghemite nanoparticles is investigated using atomistic Monte Carlo simulation. The computer modeling is carried on hollow nanostructures as a function of size and shell thickness. It is found that the large contribution of the surface anisotropy imposes a “throttled” spin structure where the moments located at the outer surface tend to orient normal to the surface while those located at the inner surface appear to be more aligned. For increasing values of surface anisotropy in the frame of a radial model, the magnetic moments become radially oriented either inward or outward giving rise to a “hedgehog” configuration with nearly zero net magnetization. We also show the effect of the size of hollow nanoparticle on the spin behavior where the spin non-collinearity increases (for fixed value of surface anisotropy) as the diameter of the hollow nanoparticle increases due to the significant increase in surface-to-volume ratio, the thickness being constant. Moreover, the thickness of the hollow nanoparticle shell influences the spin configuration and thus the relation between surface anisotropy and the size or the thickness of the hollow nanoparticle is established.

  14. Preparation and photocatalytic activity of hollow ZnSe microspheres via Ostwald ripening

    International Nuclear Information System (INIS)

    Zhang Lihui; Yang Heqing; Xie Xiaoli; Zhang Fenghua; Li Li

    2009-01-01

    Hollow ZnSe microspheres were prepared via a facile hydrothermal reaction of Zn(AC) 2 .2H 2 O with Na 2 SeO 3 and ethylene glycol in NaOH solution at 180 deg. C for 12 h. The products were characterized by means of X-ray diffraction, scanning electron microscopy, transmission electron microscopy and Raman spectrum. The hollow microspheres with the diameters of about 2 μm are constructed from ZnSe nanoparticles with the cubic zinc blende structure, the size of hollow interiors and constituent ZnSe nanodots can be tuned by changing the reaction time. The hollow microspheres are formed via an Ostwald ripening process. Photoluminescence and photocatalytic activity of the hollow ZnSe microspheres were studied at room temperature. The results indicate that the hollow microspheres constructed from ZnSe nanoparticles display a strong near-band edge emission at 479 nm and a very weak deep defect (DD) related emission at 556 nm and a high photocatalytic activity in the photodegradation of methyl orange. The photodegradation of methyl orange catalyzed by the ZnSe microspheres is a pseudo first-order reaction

  15. Periodic organosilica hollow nanospheres as anode materials for lithium ion rechargeable batteries.

    Science.gov (United States)

    Sasidharan, Manickam; Nakashima, Kenichi; Gunawardhana, Nanda; Yokoi, Toshiyuki; Ito, Masanori; Inoue, Masamichi; Yusa, Shin-ichi; Yoshio, Masaki; Tatsumi, Takashi

    2011-11-01

    Polymeric micelles with core-shell-corona architecture have been found to be the efficient colloidal templates for synthesis of periodic organosilica hollow nanospheres over a broad pH range from acidic to alkaline media. In alkaline medium, poly (styrene-b-[3-(methacryloylamino)propyl] trimethylammonium chloride-b-ethylene oxide) (PS-PMAPTAC-PEO) micelles yield benzene-silica hollow nanospheres with molecular scale periodicity of benzene groups in the shell domain of hollow particles. Whereas, an acidic medium (pH 4) produces diverse hollow particles with benzene, ethylene, and a mixture of ethylene and dipropyldisulfide bridging functionalities using poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) micelles. These hollow particles were thoroughly characterized by powder X-ray diffraction (XRD), dynamic light scattering (DLS), thermogravimetric analysis (TG/DTA), Fourier transformation infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), magic angle spinning-nuclear magnetic resonance ((29)Si MAS NMR and (13)CP-MAS NMR), Raman spectroscopy, and nitrogen adsorption/desorption analyses. The benzene-silica hollow nanospheres with molecular scale periodicity in the shell domain exhibit higher cycling performance of up to 300 cycles in lithium ion rechargeable batteries compared with micron-sized dense benzene-silica particles.

  16. A simple approach to hollow maxillary complete denture fabrication: An innovative technique

    Directory of Open Access Journals (Sweden)

    Kathleen Manuela D'souza

    2017-01-01

    Full Text Available A severely atrophic maxillary arch exhibits reduced denture bearing area and increased inter-ridge distance, thus, affecting retention of the complete denture. Such clinical situations necessitate the fabrication of a hollow complete denture to reduce the weight of the prosthesis and increase retention. This article describes a simple technique to fabricate a hollow maxillary complete denture using salt and thermoplastic poly (methyl methacrylate sheet. The vacuum-formed thermoplastic matrix regulates the quantity of salt and determines its placement in the unpolymerized denture base material during the denture packing stage. The matrix lining the hollow cavity also aids to reinforce the hollow denture base.

  17. Mesoscale cavities in hollow-core waveguides for quantum optics with atomic ensembles

    Directory of Open Access Journals (Sweden)

    Haapamaki C.M.

    2016-08-01

    Full Text Available Single-mode hollow-core waveguides loaded with atomic ensembles offer an excellent platform for light–matter interactions and nonlinear optics at low photon levels. We review and discuss possible approaches for incorporating mirrors, cavities, and Bragg gratings into these waveguides without obstructing their hollow cores. With these additional features controlling the light propagation in the hollow-core waveguides, one could potentially achieve optical nonlinearities controllable by single photons in systems with small footprints that can be integrated on a chip. We propose possible applications such as single-photon transistors and superradiant lasers that could be implemented in these enhanced hollow-core waveguides.

  18. Synthesis and upconversion luminescence properties of YF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers derived from Y{sub 2}O{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers

    Energy Technology Data Exchange (ETDEWEB)

    Li Dan; Dong Xiangting, E-mail: dongxiangting888@163.com; Yu Wensheng; Wang Jinxian; Liu Guixia [Changchun University of Science and Technology, Key Laboratory of Applied Chemistry and Nanotechnology at Universities of Jilin Province (China)

    2013-06-15

    YF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers were successfully fabricated via fluorination of the relevant Y{sub 2}O{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers which were obtained by calcining the electrospun PVP/[Y(NO{sub 3}){sub 3} + Yb(NO{sub 3}){sub 3} + Er(NO{sub 3}){sub 3}] composite nanofibers. The morphology and properties of the products were investigated in detail by X-ray diffraction, scanning electron microscope, transmission electron microscope, and fluorescence spectrometer. YF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers were pure orthorhombic phase with space group Pnma and were hollow-centered structure with mean diameter of 174 {+-} 22 nm, and YF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers are composed of nanoparticles with size in the range of 30-60 nm. Upconversion emission spectrum analysis manifested that YF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers emitted strong green and weak red upconversion emissions centering at 523, 545, and 654 nm, respectively. The green and red emissions were, respectively, originated from {sup 2}H{sub 11/2}/{sup 4}S{sub 3/2} {yields} {sup 4}I{sub 15/2} and {sup 4}F{sub 9/2} {yields} {sup 4}I{sub l5/2} energy levels transitions of the Er{sup 3+} ions. Moreover, the emitting colors of YF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers were located in the green region in CIE chromaticity coordinates diagram. This preparation technique could be applied to prepare other rare earth fluoride upconversion luminescence hollow nanofibers.Graphical AbstractYF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers with orthorhombic structure were synthesized by fluorination of the electrospun Y{sub 2}O{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers via a double-crucible method using NH{sub 4}HF{sub 2} as fluorinating agent. The mean diameter of YF{sub 3}:Yb{sup 3+}/Er{sup 3+} hollow nanofibers was 174 {+-} 22 nm. The fluorination method we proposed here has been proved to be an important method, as it can not only

  19. Mesoporous hollow spheres from soap bubbling.

    Science.gov (United States)

    Yu, Xianglin; Liang, Fuxin; Liu, Jiguang; Lu, Yunfeng; Yang, Zhenzhong

    2012-02-01

    The smaller and more stable bubbles can be generated from the large parent bubbles by rupture. In the presence of a bubble blowing agent, hollow spheres can be prepared by bubbling a silica sol. Herein, the trapped gas inside the bubble acts as a template. When the porogen, i.e., other surfactant, is introduced, a mesostructured shell forms by the co-assembly with the silica sol during sol-gel process. Morphological evolution emphasizes the prerequisite of an intermediate interior gas flow rate and high exterior gas flow rate for hollow spheres. The method is valid for many compositions from inorganic, polymer to their composites. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Controllable Synthesis of Functional Hollow Carbon Nanostructures with Dopamine As Precursor for Supercapacitors.

    Science.gov (United States)

    Liu, Chao; Wang, Jing; Li, Jiansheng; Luo, Rui; Shen, Jinyou; Sun, Xiuyun; Han, Weiqing; Wang, Lianjun

    2015-08-26

    N-doped hollow carbon spheres (N-HCSs) are promising candidates as electrode material for supercapacitor application. In this work, we report a facile one-step synthesis of discrete and highly dispersible N-HCSs with dopamine (DA) as a carbon precursor and TEOS as a structure-assistant agent in a mixture containing water, ethanol, and ammonia. The architectures of resultant N-HCSs, including yolk-shell hollow carbon spheres (YS-HCSs), single-shell hollow carbon spheres (SS-HCSs), and double-shells hollow carbon spheres (DS-HCSs), can be efficiently controlled through the adjustment of the amount of ammonia. To explain the relation and formation mechanism of these hollow carbon structures, the samples during the different synthetic steps, including polymer/silica spheres, carbon/silica spheres and silica spheres by combustion in air, were characterized by TEM. Electrochemical measurements performed on YS-HCSs, SS-HCSs, and DS-HCSs showed high capacitance with 215, 280, and 381 F g(-1), respectively. Moreover, all the nitrogen-doped hollow carbon nanospheres showed a good cycling stability 97.0% capacitive retention after 3000 cycles. Notably, the highest capacitance of DS-HCSs up to 381 F g(-1) is higher than the capacitance reported so far for many carbon-based materials, which may be attributed to the high surface area, hollow structure, nitrogen functionalization, and double-shell architecture. These kinds of N-doped hollow-structured carbon spheres may show promising prospects as advanced energy storage materials and catalyst supports.