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mark prausnitz

Bryce Chiang, Nitin Venugopal, Henry F Edelhauser, Mark R Prausnitz
The purpose of this work was to determine the effect of injection volume, formulation composition, and time on circumferential spread of particles, small molecules and polymeric formulation excipients in the suprachoroidal space (SCS) after microneedle injection into New Zealand White rabbit eyes ex vivo and in vivo. Microneedle injections of 25-150 μL Hank's Balanced Salt Solution (HBSS) containing 0.2 μm red-fluorescent particles and a model small molecule (fluorescein) were performed in rabbit eyes ex vivo, and visualized via flat mount...
October 11, 2016: Experimental Eye Research
Jaya M Arya, Kristopher Dewitt, Maya Scott-Garrard, Yu-Wei Chiang, Mark R Prausnitz
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...
October 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
E Stein Esser, AndreyA Romanyuk, Elena V Vassilieva, Joshy Jacob, Mark R Prausnitz, Richard W Compans, Ioanna Skountzou
Maternal and neonatal tetanus claim tens of thousands lives every year in developing countries, but could be prevented by hygienic practices and improved immunization of pregnant women. This study tested the hypothesis that skin vaccination can overcome the immunologically transformed state of pregnancy and enhance protective immunity to tetanus in mothers and their newborns. To achieve this goal, we developed microneedle patches (MNPs) that efficiently delivered unadjuvanted tetanus toxoid to skin of pregnant mice and demonstrated that this route induced superior immune responses in female mice conferring 100% survival to tetanus toxin challenge when compared to intramuscular vaccination...
August 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ying Liu, Jing Yan, Philip J Santangelo, Mark R Prausnitz
Ultrasound has been studied as a promising tool for intracellular gene delivery. In this work, we studied gene transfection of a human prostate cancer cell line exposed to megahertz pulsed ultrasound in the presence of contrast agent and assessed the efficiency of fluorescently labelled DNA delivery into cell nuclei, which is necessary for gene transfection. At the sonication conditions studied, ~30% of cells showed DNA uptake 30min after sonication, but that fraction decreased over time to ~10% of cells after 24h...
July 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Bryce Chiang, Yoo Chun Kim, Henry F Edelhauser, Mark R Prausnitz
Microneedle injection into the suprachoroidal space (SCS) enables targeted drug delivery for treatment of posterior segment diseases. This study sought to identify and characterize anatomical barriers to circumferential spread of particles in the SCS of rabbit and human cadaver eyes. These barriers could make targeting specific regions within the SCS challenging. A hollow microneedle (33-gauge, 750 μm long) was used to inject fluorescent particles into albino New Zealand White rabbit eyes ex vivo at six different positions around the limbus and a limited number of conditions in vivo...
April 2016: Experimental Eye Research
Matthew J Mistilis, Jessica C Joyce, E Stein Esser, Ioanna Skountzou, Richard W Compans, Andreas S Bommarius, Mark R Prausnitz
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...
February 29, 2016: Drug Delivery and Translational Research
Seonhee Park, Seong-O Choi, Seung-joon Paik, Seungkeun Choi, Mark Allen, Mark Prausnitz
Many bioactive molecules have intracellular targets, but have difficulty crossing the cell membrane to reach those targets. To address this difficulty, we fabricated arrays of nanoneedles to gently and simultaneously puncture 10(5) cells and thereby provide transient pathways for transport of molecules into the cells. The nanoneedles were microfabricated by etching silicon to create arrays of nanoneedles measuring 12 μm in height, tapering to a sharp tip less than 30 nm wide to facilitate puncture into cells and spaced 10 μm apart in order to have at least one nanoneedle puncture each cell in a confluent monolayer...
February 2016: Biomedical Microdevices
Prerona Chakravarty, Christopher D Lane, Thomas M Orlando, Mark R Prausnitz
UNLABELLED: Previous studies showed that carbon nanoparticles exposed to nanosecond laser pulses cause intracellular uptake of molecules. In this study, prostate cancer cells incubated with carbon-black (CB) nanoparticles and fluorescent marker compounds were exposed to 10ns laser pulses at 1064nm wavelength, after which intracellular uptake was measured by flow cytometry. Calcein and dextran (150kDa) were delivered into >50% of cells, whereas larger dextrans (≤2000kDa) were taken up by ~10% of cells...
May 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Leonard Y Chu, Ling Ye, Ke Dong, Richard W Compans, Chinglai Yang, Mark R Prausnitz
PURPOSE: This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature. METHODS: 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. RESULTS: 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...
April 2016: Pharmaceutical Research
Jaya Arya, Mark R Prausnitz
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...
October 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hyo-Jick Choi, Jae-Min Song, Brian J Bondy, Richard W Compans, Sang-Moo Kang, Mark R Prausnitz
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...
2015: PloS One
Aritra Sengupta, Roman Mezencev, John F McDonald, Mark R Prausnitz
AIM: The RNAi-mediated knockdown of gene expression is an attractive tool for research and therapeutic purposes but its implementation is challenging. Here we report on a new method based on photoacoustic delivery of siRNA developed to address some of these challenges. MATERIALS & METHODS: Physical properties and photoacoustic emission of carbon black (CB) particles upon near-infrared laser irradiation were characterized. Next, ovarian cancer cells Hey A8-F8 were exposed to near-infrared nanosecond laser pulses in the presence of siRNA targeting EGFR gene and CB particles...
2015: Nanomedicine
Yoo Chun Kim, Kyung Hee Oh, Henry F Edelhauser, Mark R Prausnitz
In this work, we tested the hypothesis that particles injected into the suprachoroidal space can be localized at the site of injection or broadly distributed throughout the suprachoroidal space by controlling polymeric formulation properties. Single hollow microneedles were inserted into the sclera of New Zealand White rabbits and injected non-biodegradable fluorescently tagged nanoparticles and microparticles suspended in polymeric formulations into the suprachoroidal space of the eye. When formulated in saline, the particles were distributed over 29-42% of the suprachoroidal space immediately after injection...
September 2015: European Journal of Pharmaceutics and Biopharmaceutics
Min-Chul Kim, Jeong Woo Lee, Hyo-Jick Choi, Yu-Na Lee, Hye Suk Hwang, Jongsang Lee, Cheol Kim, Jong Seok Lee, Carlo Montemagno, Mark R Prausnitz, Sang-Moo Kang
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...
July 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Mark R Prausnitz
No abstract text is available yet for this article.
May 2015: Nature Materials
Elena V Vassilieva, Haripriya Kalluri, Devin McAllister, Misha T Taherbhai, E Stein Esser, Winston P Pewin, Joanna A Pulit-Penaloza, Mark R Prausnitz, Richard W Compans, Ioanna Skountzou
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...
August 2015: Drug Delivery and Translational Research
James J Norman, Jyoti Gupta, Samirkumar R Patel, Sara Park, Courtney Jarrahian, Darin Zehrung, Mark R Prausnitz
We compared the ability of three intradermal delivery devices to administer an intended dose to pig skin in vivo and target that dose to the dermal rather than subcutaneous layers. The three devices were a standard hypodermic needle and syringe for the Mantoux technique, an adapter designed to facilitate proper hypodermic needle and syringe use, and a hollow microneedle. Reliability was determined as the percentage of the administered dose that entered the skin, as opposed to remaining in the device or on the skin surface...
April 2014: Drug Delivery and Translational Research
Rhonda C Kines, Vladimir Zarnitsyn, Teresa R Johnson, Yuk-Ying S Pang, Kizzmekia S Corbett, John D Nicewonger, Anu Gangopadhyay, Man Chen, Jie Liu, Mark R Prausnitz, John T Schiller, Barney S Graham
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...
2015: PloS One
Bruce Y Lee, Sarah M Bartsch, Mercy Mvundura, Courtney Jarrahian, Kristina M Zapf, Kathleen Marinan, Angela R Wateska, Bill Snyder, Savitha Swaminathan, Erica Jacoby, James J Norman, Mark R Prausnitz, Darin Zehrung
BACKGROUND: New vaccine technologies may improve the acceptability, delivery (potentially enabling self-administration), and product efficacy of influenza vaccines. One such technology is the microneedle patch (MNP), a skin delivery technology currently in development. Although MNPs hold promise in preclinical studies, their potential economic and epidemiologic impacts have not yet been evaluated. METHODS: We utilized a susceptible-exposed-infectious-recovered (SEIR) transmission model linked to an economic influenza outcomes model to assess the economic value of introducing the MNP into the current influenza vaccine market in the United States from the third-party payer and societal perspectives...
September 8, 2015: Vaccine
Chris Edens, Marcus L Collins, James L Goodson, Paul A Rota, Mark R Prausnitz
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...
September 8, 2015: Vaccine
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