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Analysis of the Mechanical Failure of Polymer Microneedles by Axial Force
박정환,Mark R. Prausnitz 한국물리학회 2010 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.56 No.4
A polymeric microneedle has been developed for drug delivery applications. The ultimate goal of the polymeric microneedle is insertion into the specified region without failure for effective transdermal drug delivery. The mechanical failure of various geometries of microneedles by axial load was modeled using the Euler formula and the Johnson formula to predict the failure force of taperedcolumn microneedles. These formulas were compared with measured data to identify the mechanical behavior of microneedles by determining the critical factors, including the actual length and the end-fixed factor. The comparison of the two formulas with the data showed good agreement at an end-fixity (K) of 0.7. This value means that a microneedle column has one fixed end and one pinned end and that part of the microneedle is overloaded by an axial load. When the aspect ratio of length-to-equivalent diameter is 12:1 at Young’s modulus of 3 GPa, there is a transition from the Euler region to the Johnson region due to the decreased length and the increased base diameter of the microneedle. A polymer having a stiffness of less than 3 GPa would follow the Euler formula. A 12:1 aspect ratio of length-to-equivalent diameter of the microneedle is a mechanical indicator determining the failure mode between elastic buckling and inelastic buckling at Young’s modulus of less than 3 GPa for polymer. Microneedles with an aspect ratio of length-to-equivalent diameter below 12:1 and Young’s modulus of more than 3 GPa are recommended for reducing sudden failure by buckling and for successfully inserting a microneedle into the skin.
Polymeric Tube-Shaped Devices with Controlled Geometry for Programmed Drug Delivery
박민,최영빈,박천권,이승호,이지은,조은빛,Mark R. Prausnitz 한국고분자학회 2012 Macromolecular Research Vol.20 No.9
We developed a modular tube-shaped device as a proof of principle to enable the programmed release of encapsulated molecules for controlled drug delivery. Each drug-delivery tube module was prepared by assembling two separate silicone tubes in a series, one filled with a model compound (sodium fluorescein) and the other with a diffusional barrier material (polyethylene oxide, PEO). We varied the length of the PEO-filled tubes to control the release from the drug-delivery tube devices. The onset times and periods of drug release increased with the length of the PEO tube. To program the drug release, therefore, we prepared devices with combinations of drug-delivery tube modules with different lengths of PEO-filled tubes. Using PEO-filled tubes with very different lengths achieved a pulsatile drug release while a continuous drug release was realized by using PEO-filled tubes with small differences in length. We concluded that the modular combination of drug-delivery tubes, each composed of a diffusionbarrier tube of different length, demonstrates good potential for applications in programmed drug delivery.
Song, J.M.,Kim, Y.C.,Barlow, P.G.,Hossain, M.J.,Park, K.M.,Donis, R.O.,Prausnitz, M.R.,Compans, R.W.,Kang, S.M. Elsevier/North-Holland 2010 Antiviral research Vol.88 No.2
To develop a more effective vaccination method against H5N1 virus, we investigated the immunogenicity and protective efficacy after skin vaccination using microneedles coated with influenza virus-like particles containing hemagglutinin derived from A/Vietnam/1203/04 H5N1 virus (H5 VLPs). A single microneedle vaccination of mice with H5 VLPs induced increased levels of antibodies and provided complete protection against lethal challenge without apparent disease symptoms. In contrast, intramuscular injection with the same vaccine dose showed low levels of antibodies and provided only partial protection accompanied by severe body weight loss. Post-challenge analysis suggested that improved protection was associated with lower lung viral titers and enhanced generation of recall antibody secreting cells by microneedle vaccination. Thus, this study provides evidence that skin delivery of H5 VLP vaccines using microneedles designed for self-administration induces improved protection compared to conventional intramuscular immunization.
Nitric-acid Hydrolysis of Miscanthus giganteus to Sugars Fermented to Bioethanol
Fuxin Yang,Waheed Afzal,Kun Cheng,Nian Liu,Markus Pauly,Alexis T. Bell,Zhigang Liu,John M. Prausnitz 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.2
Miscanthus giganteus (M. giganteus) is a promising feedstock for the production of bioethanol or biochemicals. Using only dilute nitric acid, this work describes a two-step process for hydrolyzing hemicellulose and cellulose to fermentable sugars. Primary variables were temperature and reaction time. The solid-to-liquid mass ratio was 1:8. No enzymes were used. In the first step, M. giganteus was contacted with 0.5 wt.% nitric acid at temperatures between 120 and 160°C for 5 to 40 min. The second step used 0.5 or 0.75 wt.% nitric acid at temperatures between 180 and 210°C for less than 6 min. Under selected conditions, almost all hemicellulose and 58% cellulose were transferred to the liquid phase. Small amounts of degradation products were observed. The xylose solution obtained from the nitric-acid hydrolysis was fermented for 96 h and the glucose solution for 48 h to yield 0.41 g ethanol/g xylose and 0.46 g ethanol/g glucose. To characterize residual solids and the liquor from both steps, nuclear-magneticresonance (NMR) spectroscopy was performed for each fraction. The analytical data indicate that the liquid phase from Steps 1 and 2 contain little lignin or lignin derivatives.
Kim, M.C.,Lee, J.W.,Choi, H.J.,Lee, Y.N.,Hwang, H.S.,Lee, J.,Kim, C.,Lee, J.S.,Montemagno, C.,Prausnitz, M.R.,Kang, S.M. Elsevier Science Publishers 2015 Journal of controlled release Vol.210 No.-
A broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. This study developed a minimally-invasive microneedle (MN) patch for skin vaccination with virus-like particles containing influenza virus heterologous M2 extracellular (M2e) domains (M2e5x VLPs) as a universal vaccine candidate without adjuvants. The stability of M2e5x VLP-coated microneedles was maintained for 8weeks at room temperature without losing M2e antigenicity and immunogenicity. MN skin immunization induced strong humoral and mucosal M2e antibody responses and conferred cross-protection against heterosubtypic H1N1, H3N2, and H5N1 influenza virus challenges. In addition, M2e5x VLP MN skin vaccination induced T-helper type 1 responses such as IgG2a isotype antibodies and IFN-γ producing cells at higher levels than those by conventional intramuscular injection. These potential immunological and logistic advantages for skin delivery of M2e5x VLP MN vaccines could offer a promising approach to develop an easy-to-administer universal influenza vaccine.