The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Tejal A Desai - One of the best experts on this subject based on the ideXlab platform.
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Reversible inhibition of efflux transporters by hydrogel Microdevices.
European Journal of Pharmaceutics and Biopharmaceutics, 2019Co-Authors: Elizabeth S. Levy, Karen E. Samy, Nicholas G. Lamson, Kathryn A. Whitehead, Deanna L. Kroetz, Tejal A DesaiAbstract:Oral drug delivery is a preferred administration route due to its low cost, high patient compliance and fewer adverse events compared to intravenous administration. However, many pharmaceuticals suffer from poor solubility and low oral bioavailability. One major factor that contributes to low bioavailability are efflux transporters which prevent drug absorption through intestinal epithelial cells. P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are two important efflux transporters in the intestine functioning to prevent toxic materials from entering systemic circulation. However, due to its broad substrate specificity, P-gp limits the absorption of many therapeutics, including chemotherapeutics and antibacterial agents. Methods to inhibit P-gp with competitive inhibitors have not been clinically successful. Here, we show that micron scale devices (Microdevices) made from a commonly used biomaterial, polyethylene glycol (PEG), inhibit P-gp through a biosimilar mucus in Caco-2 cells and that transporter function is restored when the Microdevices are removed. Microdevices were shown to inhibit P-gp mediated transport of calcein AM, doxorubicin, and rhodamine 123 (R123) and BCRP mediated transport of BODIPY-FL-prazosin. When in contact with Caco-2 cells, Microdevices decrease the cell surface amount of P-gp without affecting the passive transport. Moreover, there was an increase in mucosal to serosal transport of R123 with Microdevices in an ex-vivo mouse model and increased absorption in vivo. This biomaterial-based approach to inhibit efflux transporters can be applied to a range of drug delivery systems and allows for a nonpharmacologic method to increase intestinal drug absorption while limiting toxic effects.
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fabrication of sealed nanostraw Microdevices for oral drug delivery
ACS Nano, 2016Co-Authors: Cade B. Fox, Hariharasudhan D. Chirra, Yuhong Cao, Nicholas A. Melosh, Cameron L Nemeth, Rachel W Chevalier, Tejal A DesaiAbstract:The oral route is preferred for systemic drug administration and provides direct access to diseased tissue of the gastrointestinal (GI) tract. However, many drugs have poor absorption upon oral administration due to damaging enzymatic and pH conditions, mucus and cellular permeation barriers, and limited time for drug dissolution. To overcome these limitations and enhance oral drug absorption, micron-scale devices with planar, asymmetric geometries, termed Microdevices, have been designed to adhere to the lining of the GI tract and release drug at high concentrations directly toward GI epithelium. Here we seal Microdevices with nanostraw membranes—porous nanostructured biomolecule delivery substrates—to enhance the properties of these devices. We demonstrate that the nanostraws facilitate facile drug loading and tunable drug release, limit the influx of external molecules into the sealed drug reservoir, and increase the adhesion of devices to epithelial tissue. These findings highlight the potential of na...
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Planar Microdevices for Enhanced In Vivo Retention and Oral Bioavailability of Poorly Permeable Drugs
Advanced Healthcare Materials, 2014Co-Authors: Hariharasudhan D. Chirra, Ling Shao, Natalie A. Ciaccio, Cade B. Fox, Jennifer M. Wade, Tejal A DesaiAbstract:The development of novel oral drug delivery platforms for administering therapeutics in a safe and effective manner through the harsh gastrointestinal environment is of great importance. Here, the use of engineered thin planar poly(methyl methacrylate) (PMMA) Microdevices is tested to enhance oral bioavailability of acyclovir, a poorly permeable drug. Acyclovir is loaded into the unidirectional drug releasing microdevice reservoirs using a drug entrapping photocross-linkable hydrogel matrix. An increase in acyclovir permeation across in vitro caco-2 monolayer is seen in the presence of Microdevices as compared with acyclovir-entrapped hydrogels or free acyclovir solution. Cell proliferation studies show that Microdevices are relatively nontoxic in nature for use in in vivo studies. Enhanced in vivo retention of Microdevices is observed as their thin side walls experience minimal peristaltic shear stress as compared with spherical microparticles. Unidirectional acyclovir release and enhanced retention of Microdevices achieve a 4.5-fold increase in bioavailability in vivo as compared with an oral gavage of acyclovir solution with the same drug mass. The enhanced oral bioavailability results suggest that thin, planar, bioadhesive, and unidirectional drug releasing Microdevices will significantly improve the systemic and localized delivery of a broad range of oral therapeutics in the near future.
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multi reservoir bioadhesive Microdevices for independent rate controlled delivery of multiple drugs
Small, 2012Co-Authors: Hariharasudhan D. Chirra, Tejal A DesaiAbstract:A variety of oral administrative systems such as enterically coated tablets, capsules, particles, and liposomes have been developed to improve oral bioavailability of drugs. However, they suffer from poor intestinal localization and therapeutic efficacy due to the various physiological conditions and high shear fluid flow. Fabrication of novel Microdevices combined with the introduction of controlled release, improved adhesion, selective targeting, and tissue permeation may overcome these issues and potentially diminish the toxicity and high frequency of conventional oral administration. Herein, thin, asymmetric, poly(methyl methacrylate); PMMA Microdevices were fabricated with multiple reservoirs using photolithography and reactive ion etching. They were loaded with different individual model drug in each reservoir. Enhanced bioadhesion of the Microdevices was observed in the presence of a conjugated of targeting protein; tomato lectin to the PMMA surface. As compared to drug encompassing hydrogels, an increase in drug permeation across the caco-2 monolayer was noticed in the presence of a microdevice loaded with the same drug-hydrogel system. Also, the release of multiple drugs from their respective reservoirs was found to be independent from each other. The use of different hydrogel systems in each reservoir showed differences in the controlled release of the respective drugs over the same period of release. These results suggest that in the future, the microfabricated unidirectional multi-drug releasing devices will have an impact over the oral administration of a broad range of therapeutics.
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microfabricated devices for enhanced bioadhesive drug delivery attachment to and small molecule release through a cell monolayer under flow
Small, 2009Co-Authors: Kristy M Ainslie, Rachel D Lowe, Tristan T Beaudette, Lamar Petty, Eric M Bachelder, Tejal A DesaiAbstract:The development of a novel microfabricated device for oral drug delivery that overcomes many of the common barriers present in the gastrointestinal tract is reported. Specifically, the attachment of targeting ligands, subsequent device binding, and small molecule release from the Microdevices in flow are investigated. A diffusion chamber that permits the simultaneous study of particle binding and small-molecule release under physiologically relevant shear conditions is developed. It is observed that once the particles bind to the cell surface, they remain attached. A small fraction of the devices detach in flow; however, most of these devices readily reattach to the cell layer in a new location. This steady-state density of Microdevices is most likely the result of larger order microdevice clusters releasing their loose interactions with nearby Microdevices, shifting slightly downstream, and subsequently reattaching to the cell monolayer. The release of a model small molecule from Microdevices over time is roughly linear and approximately ten times greater than that observed with the small molecule alone. Overall, the preparation and characterization of an oral drug-delivery microdevice system capable of both targeting and asymmetric release in flow is reported.
Yuan Yuan - One of the best experts on this subject based on the ideXlab platform.
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protein a based antibody immobilization onto polymeric Microdevices for enhanced sensitivity of enzyme linked immunosorbent assay
Biotechnology and Bioengineering, 2009Co-Authors: Yuan Yuan, Hongyan HeAbstract:Highly efficient antibody immobilization is extremely crucial for the development of high-performance polymeric Microdevices for enzyme-linked immunosorbent assay (ELISA). In this article, a site-selective tyrosinase (TR)-catalyzed protein A strategy for antibody immobilization was developed to enhance the sensitivity of ELISA in poly-(methyl methacrylate) (PMMA) microchannels for interferon-γ (IFN-γ) assay. To effectively immobilize the target antibodies, oxygen plasma was first used to activate the inert PMMA. This is followed by poly(ethyleneimine) (PEI) coating, an amine-containing functional polymer. For comparison, protein A was also immobilized through the commonly used amine-glutaraldehyde (GA) chemistry. Oxygen plasma treatment effectively increased the amount of PEI attachment and subsequent binding efficiency of the primary antibody. The antibody immobilized via TR-catalyzed protein A was able to provide much better specific antigen capture efficiency than GA chemistry due to the optimal spacing and orientation. Consequently, by using this new method, the detection signal and the signal-to-noise ratio of the ELISA immunoassay in Microdevices were all significantly improved. In comparison to the standard assay carried out in the 96-well microtiter plate, the treated microchannels exhibited a broader detection range and a shorter detection time. And the detection limit was also decreased to 20 pg/mL, much lower than that obtained in other Microdevices. Biotechnol. Bioeng. 2009; 102: 891–901. © 2008 Wiley Periodicals, Inc.
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protein a based antibody immobilization onto polymeric Microdevices for enhanced sensitivity of enzyme linked immunosorbent assay
Biotechnology and Bioengineering, 2009Co-Authors: Yuan Yuan, James L LeeAbstract:Highly efficient antibody immobilization is extremely crucial for the development of high-performance polymeric Microdevices for enzyme-linked immunosorbent assay (ELISA). In this article, a site-selective tyrosinase (TR)-catalyzed protein A strategy for antibody immobilization was developed to enhance the sensitivity of ELISA in poly-(methyl methacrylate) (PMMA) microchannels for interferon-gamma (IFN-gamma) assay. To effectively immobilize the target antibodies, oxygen plasma was first used to activate the inert PMMA. This is followed by poly(ethyleneimine) (PEI) coating, an amine-containing functional polymer. For comparison, protein A was also immobilized through the commonly used amine-glutaraldehyde (GA) chemistry. Oxygen plasma treatment effectively increased the amount of PEI attachment and subsequent binding efficiency of the primary antibody. The antibody immobilized via TR-catalyzed protein A was able to provide much better specific antigen capture efficiency than GA chemistry due to the optimal spacing and orientation. Consequently, by using this new method, the detection signal and the signal-to-noise ratio of the ELISA immunoassay in Microdevices were all significantly improved. In comparison to the standard assay carried out in the 96-well microtiter plate, the treated microchannels exhibited a broader detection range and a shorter detection time. And the detection limit was also decreased to 20 pg/mL, much lower than that obtained in other Microdevices.
Hongyan He - One of the best experts on this subject based on the ideXlab platform.
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protein a based antibody immobilization onto polymeric Microdevices for enhanced sensitivity of enzyme linked immunosorbent assay
Biotechnology and Bioengineering, 2009Co-Authors: Yuan Yuan, Hongyan HeAbstract:Highly efficient antibody immobilization is extremely crucial for the development of high-performance polymeric Microdevices for enzyme-linked immunosorbent assay (ELISA). In this article, a site-selective tyrosinase (TR)-catalyzed protein A strategy for antibody immobilization was developed to enhance the sensitivity of ELISA in poly-(methyl methacrylate) (PMMA) microchannels for interferon-γ (IFN-γ) assay. To effectively immobilize the target antibodies, oxygen plasma was first used to activate the inert PMMA. This is followed by poly(ethyleneimine) (PEI) coating, an amine-containing functional polymer. For comparison, protein A was also immobilized through the commonly used amine-glutaraldehyde (GA) chemistry. Oxygen plasma treatment effectively increased the amount of PEI attachment and subsequent binding efficiency of the primary antibody. The antibody immobilized via TR-catalyzed protein A was able to provide much better specific antigen capture efficiency than GA chemistry due to the optimal spacing and orientation. Consequently, by using this new method, the detection signal and the signal-to-noise ratio of the ELISA immunoassay in Microdevices were all significantly improved. In comparison to the standard assay carried out in the 96-well microtiter plate, the treated microchannels exhibited a broader detection range and a shorter detection time. And the detection limit was also decreased to 20 pg/mL, much lower than that obtained in other Microdevices. Biotechnol. Bioeng. 2009; 102: 891–901. © 2008 Wiley Periodicals, Inc.
James L Lee - One of the best experts on this subject based on the ideXlab platform.
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protein a based antibody immobilization onto polymeric Microdevices for enhanced sensitivity of enzyme linked immunosorbent assay
Biotechnology and Bioengineering, 2009Co-Authors: Yuan Yuan, James L LeeAbstract:Highly efficient antibody immobilization is extremely crucial for the development of high-performance polymeric Microdevices for enzyme-linked immunosorbent assay (ELISA). In this article, a site-selective tyrosinase (TR)-catalyzed protein A strategy for antibody immobilization was developed to enhance the sensitivity of ELISA in poly-(methyl methacrylate) (PMMA) microchannels for interferon-gamma (IFN-gamma) assay. To effectively immobilize the target antibodies, oxygen plasma was first used to activate the inert PMMA. This is followed by poly(ethyleneimine) (PEI) coating, an amine-containing functional polymer. For comparison, protein A was also immobilized through the commonly used amine-glutaraldehyde (GA) chemistry. Oxygen plasma treatment effectively increased the amount of PEI attachment and subsequent binding efficiency of the primary antibody. The antibody immobilized via TR-catalyzed protein A was able to provide much better specific antigen capture efficiency than GA chemistry due to the optimal spacing and orientation. Consequently, by using this new method, the detection signal and the signal-to-noise ratio of the ELISA immunoassay in Microdevices were all significantly improved. In comparison to the standard assay carried out in the 96-well microtiter plate, the treated microchannels exhibited a broader detection range and a shorter detection time. And the detection limit was also decreased to 20 pg/mL, much lower than that obtained in other Microdevices.
Xiangchun Xuan - One of the best experts on this subject based on the ideXlab platform.
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joule heating enabled electrothermal enrichment of nanoparticles in insulator based dielectrophoretic Microdevices
Electrophoresis, 2020Co-Authors: Amirreza Malekanfard, Zhijian Liu, Le Song, Akshay Kale, Cheng Zhang, Yongxin Song, Xiangchun XuanAbstract:Insulator-based dielectrophoresis (iDEP) exploits the electric field gradients formed around insulating structures to manipulate particles for diverse microfluidic applications. Compared to the traditional electrode-based dielectrophoresis, iDEP Microdevices have the advantages of easy fabrication, free of water electrolysis, and robust structure, etc. However, the presence of in-channel insulators may cause thermal effects because of the locally amplified Joule heating of the fluid. The resulting electrothermal flow circulations are exploited in this work to trap and concentrate nanoscale particles (of 100 nm diameter and less) in a ratchet-based iDEP microdevice. Such Joule heating-enabled electrothermal enrichment of nanoparticles are found to grow with the increase of alternating current or direct current electric field. It also becomes more effective for larger particles and in a microchannel with symmetric ratchets. Moreover, a depth-averaged numerical model is developed to understand and simulate the various parametric effects, which is found to predict the experimental observations with a good agreement.
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numerical modeling of joule heating effects in insulator based dielectrophoresis Microdevices
Electrophoresis, 2013Co-Authors: Akshay Kale, Saurin Patel, Xiangchun XuanAbstract:Insulator-based DEP (iDEP) has been established as a powerful tool for manipulating particles in microfluidic devices. However, Joule heating may become an issue in iDEP Microdevices due to the local amplification of electric field around the insulators. This results in an electrothermal force that can manifest itself in the flow field in the form of circulations, thus affecting the particle motion. We develop herein a transient, 3D, full-scale numerical model to study Joule heating and its effects on the coupled transport of charge, heat, and fluid in an iDEP device with a rectangular constriction microchannel. This model is validated by comparing the simulation results with the experimentally obtained fluid flow patterns and particle images that were reported in our recent works. It identifies a significant difference in the time scales of the electric, temperature, and flow fields in iDEP Microdevices. It also predicts the locations of electrothermal flow circulations in different halves of the channel at the upstream and downstream of the constriction.