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mark prausnitz

Mark R Prausnitz
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, skininsertion 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...
March 24, 2017: Annual Review of Chemical and Biomolecular Engineering
Aritra Sengupta, Michael D Gray, Sean C Kelly, Stefany Y Holguin, Naresh N Thadhani, Mark R Prausnitz
Previous studies have shown that exposure of carbon black nanoparticles to nanosecond pulsed near-infrared laser causes intracellular delivery of molecules through hypothesized transient breaks in the cell membrane. The goal of this study is to determine the underlying mechanisms of sequential energy transfer from laser light to nanoparticle to fluid medium to cell. We found that laser pulses on a timescale of 10 ns rapidly heat carbon nanoparticles to temperatures on the order of 1200 K. Heat is transferred from the nanoparticles to the surrounding aqueous medium on a similar timescale, causing vaporization of the surrounding water and generation of acoustic emissions...
March 28, 2017: Biophysical Journal
Jaya Arya, Sebastien Henry, Haripriya Kalluri, Devin V McAllister, Winston P Pewin, Mark R Prausnitz
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...
June 2017: Biomaterials
Javier O Morales, Kristin R Fathe, Ashlee Brunaugh, Silvia Ferrati, Song Li, Miguel Montenegro-Nicolini, Zeynab Mousavikhamene, Jason T McConville, Mark R Prausnitz, Hugh D C Smyth
Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers...
February 13, 2017: AAPS Journal
Bryce Chiang, Nitin Venugopal, Hans E Grossniklaus, Jae Hwan Jung, Henry F Edelhauser, Mark R Prausnitz
Purpose: To determine the effect of injection volume and formulation of a microneedle injection into the suprachoroidal space (SCS) on SCS thickness and closure kinetics. Methods: 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...
January 1, 2017: Investigative Ophthalmology & Visual Science
Bryce Chiang, Ke Wang, C Ross Ethier, Mark R Prausnitz
Purpose: To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. Methods: 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...
January 1, 2017: Investigative Ophthalmology & Visual Science
Hung-Wei Yang, Ling Ye, Xin Dong Guo, Chinglai Yang, Richard W Compans, Mark R Prausnitz
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.
January 2017: Advanced Healthcare Materials
Samirkumar R Patel, Mark R Prausnitz
No abstract text is available yet for this article.
December 2016: Journal of Ocular Pharmacology and Therapeutics
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...
December 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...
April 2017: 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
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