The Experts below are selected from a list of 4209 Experts worldwide ranked by ideXlab platform
Mark R Prausnitz - One of the best experts on this subject based on the ideXlab platform.
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tolerability usability and acceptability of dissolving Microneedle patch administration in human subjects
Biomaterials, 2017Co-Authors: Jaya Arya, Sebastien Henry, Devin V Mcallister, Haripriya Kalluri, Winston Pewin, Mark R PrausnitzAbstract: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.
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Microneedles for drug and vaccine delivery
Advanced Drug Delivery Reviews, 2012Co-Authors: Jung-hwan Park, Mark R PrausnitzAbstract:Abstract 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.
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Measles vaccination using a Microneedle patch.
Vaccine, 2012Co-Authors: Chris Edens, Marcus L. Collins, Jessica D Ayers, Paul A. Rota, Mark R PrausnitzAbstract: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.
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stability of influenza vaccine coated onto Microneedles
Biomaterials, 2012Co-Authors: Hyo Jick Choi, Brian J. Bondy, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:A Microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of Microneedles have demonstrated effective vaccination using freshly prepared Microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of Microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the Microneedle coating matrix damages influenza vaccine coated onto Microneedles. In vitro studies showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using Microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated Microneedles.
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infusion pressure and pain during Microneedle injection into skin of human subjects
Biomaterials, 2011Co-Authors: Jyoti Gupta, Brian J. Bondy, Eric I Felner, Sohyun S Park, Mark R PrausnitzAbstract: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 caused 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.
Hyungil Jung - One of the best experts on this subject based on the ideXlab platform.
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droplet born air blowing novel dissolving Microneedle fabrication
Journal of Controlled Release, 2013Co-Authors: Jung Dong Kim, M Kim, Huisuk Yang, Kwang Lee, Hyungil JungAbstract: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.
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drawing lithography for Microneedles a review of fundamentals and biomedical applications
Biomaterials, 2012Co-Authors: Hyungil JungAbstract: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.
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drawing lithography for Microneedles a review of fundamentals and biomedical applications
Biomaterials, 2012Co-Authors: Hyungil JungAbstract: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.
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dissolving Microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose
Biomaterials, 2011Co-Authors: Hyungil JungAbstract:Dissolving Microneedles, three-dimensional polymer structures with microscale cross-sectional dimensions, have been introduced as a means of safe transdermal drug delivery. Most dissolving Microneedles have been fabricated using a traditional micro-casting method that cures biopolymers within three-dimensional mold, nevertheless, repeated molding process may cause damage to encapsulated drugs, a critical hurdle for clinical application. Here, we describe the stepwise controlled drawing technique that can directly fabricate dissolving Microneedle from maltose by precise controlling the drawing time and the viscosity of the maltose. Controlled drawing shaped the particular sharp-conical Microneedles of 1200 μm length with tip diameter of 60 μm, and dissolved within 20 min in-vivo after inserting to the skin. This technique surpasses the limitations of micro-casting for dissolving Microneedle. Furthermore, transdermal delivery of impermeable hydrophilic molecules such as ascorbic acid-2-glucoside and niacinamide was confirmed as inhibition of cutaneous hypermelanosis. We anticipate that controlled drawing technique will be suitable to design dissolving Microneedles for use in minimally invasive transcutaneous drug delivery to patients.
Sang-moo Kang - One of the best experts on this subject based on the ideXlab platform.
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stability of influenza vaccine coated onto Microneedles
Biomaterials, 2012Co-Authors: Hyo Jick Choi, Brian J. Bondy, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:A Microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of Microneedles have demonstrated effective vaccination using freshly prepared Microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of Microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the Microneedle coating matrix damages influenza vaccine coated onto Microneedles. In vitro studies showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using Microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated Microneedles.
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dose sparing enabled by skin immunization with influenza virus like particle vaccine using Microneedles
Journal of Controlled Release, 2010Co-Authors: Fu-shi Quan, Mark R Prausnitz, Richard W. Compans, Sang-moo KangAbstract:To address the limitations of conventional influenza vaccine manufacturing and delivery, this study investigated administration of virus-like particle (VLP) influenza vaccine using a Microneedle patch. The goal was to determine if skin immunization with influenza VLP vaccine using Microneedles enables dose sparing. We found that low-dose influenza (A/PR/8/34 H1N1) VLP vaccination using Microneedles was more immunogenic than low-dose intramuscular (IM) vaccination and similarly immunogenic as high-dose IM vaccination in a mouse model. With a 1 μg dose of vaccine, both routes showed similar immune responses and protective efficacy, with Microneedle vaccination being more effective in inducing recall antibody responses in lungs and antibody secreting cells in bone marrow. With a low dose of vaccine (0.3 μg), Microneedle vaccination induced significantly superior protective immunity, which included binding and functional antibodies as well as complete protection against a high dose lethal infection with A/PR/8/34 virus, whereas IM immunization provided only partial (40%) protection. Therefore, this study demonstrates that Microneedle vaccination in the skin confers more effective protective immunity at a lower dose, thus providing vaccine dose-sparing effects.
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formulation and coating of Microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity
Journal of Controlled Release, 2010Co-Authors: Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:Abstract Microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. However, dip coating Microneedles with influenza vaccine can reduce antigen activity. In this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved Microneedle coating formulations that protect the antigen from activity loss. After coating Microneedles using a standard vaccine formulation, the stability of influenza vaccine was reduced to just 2%, as measured by hemagglutination activity. The presence of carboxymethylcellulose, which was added to increase viscosity of the coating formulation, was shown to contribute to vaccine activity loss. After screening a panel of candidate stabilizers, the addition of trehalose to the coating formulation was found to protect the antigen and retain 48–82% antigen activity for all three major strains of seasonal influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited thermal stability, such that activity loss was independent of temperature over the range of 4–37 °C for 24 h. Dynamic light scattering measurements showed that antigen activity loss was associated with virus particle aggregation, and that stabilization using trehalose largely blocked this aggregation. Finally, Microneedles using an optimized vaccine coating formulation were applied to the skin to vaccinate mice. Microneedle vaccination induced robust systemic and functional antibodies and provided complete protection against lethal challenge infection similar to conventional intramuscular injection. Overall, these results show that antigen activity loss during Microneedle coating can be largely prevented through optimized formulation and that stabilized Microneedle patches can be used for effective vaccination.
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Formulation and coating of Microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity
2010Co-Authors: Yeu Chun Kim, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:Microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. However, dip coating Microneedles with influenza vaccine can reduce antigen activity. In this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved Microneedle coating formulations that protect the antigen from activity loss. After coating Microneedles using a standard vaccine formulation, the stability of influenza vaccine was reduced to just 2%, as measured by hemagglutination activity. The presence of carboxymethylcellulose, which was added to increase viscosity of the coating formulation, was shown to contribute to vaccine activity loss. After screening a panel of candidate stabilizers, the addition of trehalose to the coating formulation was found to protect the antigen and retain 48-82% antigen activity for all three major strains of seasonal influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited thermal stability, such that activity loss was independent of temperature over the range of 4-37 ??C for 24 h. Dynamic light scattering measurements showed that antigen activity loss was associated with virus particle aggregation, and that stabilization using trehalose largely blocked this aggregation. Finally, Microneedles using an optimized vaccine coating formulation were applied to the skin to vaccinate mice. Microneedle vaccination induced robust systemic and functional antibodies and provided complete protection against lethal challenge infection similar to conventional intramuscular injection. Overall, these results show that antigen activity loss during Microneedle coating can be largely prevented through optimized formulation and that stabilized Microneedle patches can be used for effective vaccination. ?? 2009 Elsevier B.V.
Fu-shi Quan - One of the best experts on this subject based on the ideXlab platform.
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stability of influenza vaccine coated onto Microneedles
Biomaterials, 2012Co-Authors: Hyo Jick Choi, Brian J. Bondy, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:A Microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of Microneedles have demonstrated effective vaccination using freshly prepared Microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of Microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the Microneedle coating matrix damages influenza vaccine coated onto Microneedles. In vitro studies showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using Microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated Microneedles.
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dose sparing enabled by skin immunization with influenza virus like particle vaccine using Microneedles
Journal of Controlled Release, 2010Co-Authors: Fu-shi Quan, Mark R Prausnitz, Richard W. Compans, Sang-moo KangAbstract:To address the limitations of conventional influenza vaccine manufacturing and delivery, this study investigated administration of virus-like particle (VLP) influenza vaccine using a Microneedle patch. The goal was to determine if skin immunization with influenza VLP vaccine using Microneedles enables dose sparing. We found that low-dose influenza (A/PR/8/34 H1N1) VLP vaccination using Microneedles was more immunogenic than low-dose intramuscular (IM) vaccination and similarly immunogenic as high-dose IM vaccination in a mouse model. With a 1 μg dose of vaccine, both routes showed similar immune responses and protective efficacy, with Microneedle vaccination being more effective in inducing recall antibody responses in lungs and antibody secreting cells in bone marrow. With a low dose of vaccine (0.3 μg), Microneedle vaccination induced significantly superior protective immunity, which included binding and functional antibodies as well as complete protection against a high dose lethal infection with A/PR/8/34 virus, whereas IM immunization provided only partial (40%) protection. Therefore, this study demonstrates that Microneedle vaccination in the skin confers more effective protective immunity at a lower dose, thus providing vaccine dose-sparing effects.
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formulation and coating of Microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity
Journal of Controlled Release, 2010Co-Authors: Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:Abstract Microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. However, dip coating Microneedles with influenza vaccine can reduce antigen activity. In this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved Microneedle coating formulations that protect the antigen from activity loss. After coating Microneedles using a standard vaccine formulation, the stability of influenza vaccine was reduced to just 2%, as measured by hemagglutination activity. The presence of carboxymethylcellulose, which was added to increase viscosity of the coating formulation, was shown to contribute to vaccine activity loss. After screening a panel of candidate stabilizers, the addition of trehalose to the coating formulation was found to protect the antigen and retain 48–82% antigen activity for all three major strains of seasonal influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited thermal stability, such that activity loss was independent of temperature over the range of 4–37 °C for 24 h. Dynamic light scattering measurements showed that antigen activity loss was associated with virus particle aggregation, and that stabilization using trehalose largely blocked this aggregation. Finally, Microneedles using an optimized vaccine coating formulation were applied to the skin to vaccinate mice. Microneedle vaccination induced robust systemic and functional antibodies and provided complete protection against lethal challenge infection similar to conventional intramuscular injection. Overall, these results show that antigen activity loss during Microneedle coating can be largely prevented through optimized formulation and that stabilized Microneedle patches can be used for effective vaccination.
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Formulation and coating of Microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity
2010Co-Authors: Yeu Chun Kim, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:Microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. However, dip coating Microneedles with influenza vaccine can reduce antigen activity. In this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved Microneedle coating formulations that protect the antigen from activity loss. After coating Microneedles using a standard vaccine formulation, the stability of influenza vaccine was reduced to just 2%, as measured by hemagglutination activity. The presence of carboxymethylcellulose, which was added to increase viscosity of the coating formulation, was shown to contribute to vaccine activity loss. After screening a panel of candidate stabilizers, the addition of trehalose to the coating formulation was found to protect the antigen and retain 48-82% antigen activity for all three major strains of seasonal influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited thermal stability, such that activity loss was independent of temperature over the range of 4-37 ??C for 24 h. Dynamic light scattering measurements showed that antigen activity loss was associated with virus particle aggregation, and that stabilization using trehalose largely blocked this aggregation. Finally, Microneedles using an optimized vaccine coating formulation were applied to the skin to vaccinate mice. Microneedle vaccination induced robust systemic and functional antibodies and provided complete protection against lethal challenge infection similar to conventional intramuscular injection. Overall, these results show that antigen activity loss during Microneedle coating can be largely prevented through optimized formulation and that stabilized Microneedle patches can be used for effective vaccination. ?? 2009 Elsevier B.V.
Richard W. Compans - One of the best experts on this subject based on the ideXlab platform.
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stability of influenza vaccine coated onto Microneedles
Biomaterials, 2012Co-Authors: Hyo Jick Choi, Brian J. Bondy, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:A Microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of Microneedles have demonstrated effective vaccination using freshly prepared Microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of Microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the Microneedle coating matrix damages influenza vaccine coated onto Microneedles. In vitro studies showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using Microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated Microneedles.
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dose sparing enabled by skin immunization with influenza virus like particle vaccine using Microneedles
Journal of Controlled Release, 2010Co-Authors: Fu-shi Quan, Mark R Prausnitz, Richard W. Compans, Sang-moo KangAbstract:To address the limitations of conventional influenza vaccine manufacturing and delivery, this study investigated administration of virus-like particle (VLP) influenza vaccine using a Microneedle patch. The goal was to determine if skin immunization with influenza VLP vaccine using Microneedles enables dose sparing. We found that low-dose influenza (A/PR/8/34 H1N1) VLP vaccination using Microneedles was more immunogenic than low-dose intramuscular (IM) vaccination and similarly immunogenic as high-dose IM vaccination in a mouse model. With a 1 μg dose of vaccine, both routes showed similar immune responses and protective efficacy, with Microneedle vaccination being more effective in inducing recall antibody responses in lungs and antibody secreting cells in bone marrow. With a low dose of vaccine (0.3 μg), Microneedle vaccination induced significantly superior protective immunity, which included binding and functional antibodies as well as complete protection against a high dose lethal infection with A/PR/8/34 virus, whereas IM immunization provided only partial (40%) protection. Therefore, this study demonstrates that Microneedle vaccination in the skin confers more effective protective immunity at a lower dose, thus providing vaccine dose-sparing effects.
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formulation and coating of Microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity
Journal of Controlled Release, 2010Co-Authors: Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:Abstract Microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. However, dip coating Microneedles with influenza vaccine can reduce antigen activity. In this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved Microneedle coating formulations that protect the antigen from activity loss. After coating Microneedles using a standard vaccine formulation, the stability of influenza vaccine was reduced to just 2%, as measured by hemagglutination activity. The presence of carboxymethylcellulose, which was added to increase viscosity of the coating formulation, was shown to contribute to vaccine activity loss. After screening a panel of candidate stabilizers, the addition of trehalose to the coating formulation was found to protect the antigen and retain 48–82% antigen activity for all three major strains of seasonal influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited thermal stability, such that activity loss was independent of temperature over the range of 4–37 °C for 24 h. Dynamic light scattering measurements showed that antigen activity loss was associated with virus particle aggregation, and that stabilization using trehalose largely blocked this aggregation. Finally, Microneedles using an optimized vaccine coating formulation were applied to the skin to vaccinate mice. Microneedle vaccination induced robust systemic and functional antibodies and provided complete protection against lethal challenge infection similar to conventional intramuscular injection. Overall, these results show that antigen activity loss during Microneedle coating can be largely prevented through optimized formulation and that stabilized Microneedle patches can be used for effective vaccination.
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Formulation and coating of Microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity
2010Co-Authors: Yeu Chun Kim, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R PrausnitzAbstract:Microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. However, dip coating Microneedles with influenza vaccine can reduce antigen activity. In this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved Microneedle coating formulations that protect the antigen from activity loss. After coating Microneedles using a standard vaccine formulation, the stability of influenza vaccine was reduced to just 2%, as measured by hemagglutination activity. The presence of carboxymethylcellulose, which was added to increase viscosity of the coating formulation, was shown to contribute to vaccine activity loss. After screening a panel of candidate stabilizers, the addition of trehalose to the coating formulation was found to protect the antigen and retain 48-82% antigen activity for all three major strains of seasonal influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited thermal stability, such that activity loss was independent of temperature over the range of 4-37 ??C for 24 h. Dynamic light scattering measurements showed that antigen activity loss was associated with virus particle aggregation, and that stabilization using trehalose largely blocked this aggregation. Finally, Microneedles using an optimized vaccine coating formulation were applied to the skin to vaccinate mice. Microneedle vaccination induced robust systemic and functional antibodies and provided complete protection against lethal challenge infection similar to conventional intramuscular injection. Overall, these results show that antigen activity loss during Microneedle coating can be largely prevented through optimized formulation and that stabilized Microneedle patches can be used for effective vaccination. ?? 2009 Elsevier B.V.