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Article: Quantifying Tight Junction Disruption Caused by Biomimetic pH-Sensitive Hydrogel Drug Carriers.

Fisher, Omar Z / Peppas, Nicholas A

Journal of drug delivery science and technology

2011 Volume 18, Issue 1, Page(s) 47–50

Abstract: ... networks in Caco-2 monolayers. Z-stack projection images showed the lateral disruption of tight junctions ...

Abstract	Facilitation of protein transport across biomimetic polymers and carriers used in drug delivery is a subject of major importance in the field of oral delivery. Quantitative immunofluorescence of epithelial tight junctions can be a valuable tool in the evaluation of paracellular permeation enhancement and macromolecular drug absorption. The tight junctional space is composed of transmembrane protein networks that provide both mechanical support and a transport barrier. Both of these may be affected by drug delivery agents that enhance paracytosis. Imaging is the only tool that can tease apart these processes. A confocal microscopy imaging method was developed to determine the effect of microparticulate poly(methacrylic acid) grafted poly(ethylene glycol) (P(MAA-g-EG)) hydrogel drug carriers on the integrity of claudin-1 and E-cadherin networks in Caco-2 monolayers. Z-stack projection images showed the lateral disruption of tight junctions in the presence of drug carriers. Tight junction image fraction measurements showed more significant differences between membranes exposed to microparticles and a control group. Mechanical disruption was much more pronounced in the presence of P(MAA-g-EG) microparticles as compared to the effect of EDTA.
Language	English
Publishing date	2011-06-20
Publishing country	France
Document type	Journal Article
ZDB-ID	2141013-6
ISSN	1773-2247
ISSN	1773-2247
DOI	10.1016/s1773-2247(08)50006-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Polybasic Nanomatrices Prepared By UV-initiated Photopolymerization.

Fisher, Omar Z / Peppas, Nicholas A

Macromolecules

2010 Volume 42, Issue 9, Page(s) 3391–3398

Abstract: A novel method for synthesizing nanoscale polymer networks that swell in acidic media is described here using photoinitiated emulsion polymerization. These nanomatrices consist of a crosslinked core of poly[2-(diethylamino)ethyl methacrylate] surface ... ...

Abstract	A novel method for synthesizing nanoscale polymer networks that swell in acidic media is described here using photoinitiated emulsion polymerization. These nanomatrices consist of a crosslinked core of poly[2-(diethylamino)ethyl methacrylate] surface grafted with poly(ethylene glycol) (PDGP) with an average diameter of 50-150 nm. Control over mesh size, surface charge, encapsulation efficiency and in vitro biocompatibility was obtained by varying crosslinking density. The ability to image nanomatrices in their dry state using conventional scanning electron microscopy was made possible by increasing crosslinking density. Theoretical calculations of matrix mesh sizes were supported by the encapsulation of both insulin and colloidal gold 2-5 nm in diameter. The ability to sequester and control the aggregation of an inorganic phase confirmed their use as a nanocomposite matrix material. These networks could be used as imaging agents, drug delivery devices or as components of sensing devices.
Language	English
Publishing date	2010-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3436-8
ISSN	0024-9297
ISSN	0024-9297
DOI	10.1021/ma801966r
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Article ; Online: Bioinspired materials for controlling stem cell fate.

Fisher, Omar Z / Khademhosseini, Ali / Langer, Robert / Peppas, Nicholas A

Accounts of chemical research

2011 Volume 43, Issue 3, Page(s) 419–428

Abstract: Although researchers currently have limited ability to mimic the natural stem cell microenvironment, recent work at the interface of stem biology and biomaterials science has demonstrated that control over stem cell behavior with artificial ... ...

Abstract	Although researchers currently have limited ability to mimic the natural stem cell microenvironment, recent work at the interface of stem biology and biomaterials science has demonstrated that control over stem cell behavior with artificial microenvironments is quite advanced. Embryonic and adult stem cells are potentially useful platforms for tissue regeneration, cell-based therapeutics, and disease-in-a-dish models for drug screening. The major challenge in this field is to reliably control stem cell behavior outside the body. Common biological control schemes often ignore physicochemical parameters that materials scientists and engineers commonly manipulate, such as substrate topography and mechanical and rheological properties. However, with appropriate attention to these parameters, researchers have designed novel synthetic microenvironments to control stem cell behavior in rather unnatural ways. In this Account, we review synthetic microenvironments that aim to overcome the limitations of natural niches rather than to mimic them. A biomimetic stem cell control strategy is often limited by an incomplete understanding of the complex signaling pathways that drive stem cell behavior from early embryogenesis to late adulthood. The stem cell extracellular environment presents a miscellany of competing biological signals that keep the cell in a state of unstable equilibrium. Using synthetic polymers, researchers have designed synthetic microenvironments with an uncluttered array of cell signals, both specific and nonspecific, that are motivated by rather than modeled after biology. These have proven useful in maintaining cell potency, studying asymmetric cell division, and controlling cellular differentiation. We discuss recent research that highlights important biomaterials properties for controlling stem cell behavior, as well as advanced processes for selecting those materials, such as combinatorial and high-throughput screening. Much of this work has utilized micro- and nanoscale fabrication tools for controlling material properties and generating diversity in both two and three dimensions. Because of their ease of synthesis and similarity to biological soft matter, hydrogels have become a biomaterial of choice for generating 3D microenvironments. In presenting these efforts within the framework of synthetic biology, we anticipate that future researchers may exploit synthetic polymers to create microenvironments that control stem cell behavior in clinically relevant ways.
MeSH term(s)	Biocompatible Materials/chemistry ; Drug Evaluation, Preclinical ; Genome ; Hydrogels/chemistry ; Polymers/chemistry ; Stem Cells/cytology ; Tissue Engineering
Chemical Substances	Biocompatible Materials ; Hydrogels ; Polymers
Language	English
Publishing date	2011-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483291-4
ISSN	1520-4898 ; 0001-4842
ISSN (online)	1520-4898
ISSN	0001-4842
DOI	10.1021/ar900226q
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Activatable interpolymer complex-superparamagnetic iron oxide nanoparticles as magnetic resonance contrast agents sensitive to oxidative stress.

Yoo, Eunsoo / Cheng, Huaitzung A / Nardacci, Lauren E / Beaman, David J / Drinnan, Charles T / Lee, Carmen / Fishbein, Kenneth W / Spencer, Richard G / Fisher, Omar Z / Doiron, Amber L

Colloids and surfaces. B, Biointerfaces

2017 Volume 158, Page(s) 578–588

Abstract: Magnetic resonance contrast agents that can be activated in response to specific triggers hold potential as molecular biosensors that may be of great utility in non-invasive disease diagnosis. We developed an activatable agent based on superparamagnetic ... ...

Abstract	Magnetic resonance contrast agents that can be activated in response to specific triggers hold potential as molecular biosensors that may be of great utility in non-invasive disease diagnosis. We developed an activatable agent based on superparamagnetic iron oxide nanoparticles (SPIOs) that is sensitive to oxidative stress, a factor in the pathophysiology of numerous diseases. SPIOs were coated with poly(ethylene glycol) (PEG) and complexed with poly(gallol), a synthetic tannin. Hydrogen bonding between PEG and poly(gallol) creates a complexed layer around the SPIO that decreases the interaction of solute water with the SPIO, attenuating its magnetic resonance relaxivity. The complexed interpolymer nanoparticle is in an OFF state (decreased T
MeSH term(s)	Contrast Media/chemistry ; Ferric Compounds/chemistry ; Magnetic Resonance Imaging ; Magnetite Nanoparticles/chemistry ; Nanoparticles/chemistry ; Oxidative Stress ; Polyethylene Glycols/chemistry
Chemical Substances	Contrast Media ; Ferric Compounds ; Magnetite Nanoparticles ; ferric oxide (1K09F3G675) ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2017-07-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2017.07.025
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Article ; Online: Microfabrication technologies for oral drug delivery.

Sant, Shilpa / Tao, Sarah L / Fisher, Omar Z / Xu, Qiaobing / Peppas, Nicholas A / Khademhosseini, Ali

Advanced drug delivery reviews

2011 Volume 64, Issue 6, Page(s) 496–507

Abstract: Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being ... ...

Abstract	Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being explored for drug delivery applications due to their ability to combine several features such as precise shape and size into a single drug delivery vehicle. They also offer to create unique asymmetrical features incorporated into single or multiple reservoir systems maximizing contact area with the intestinal lining. Combined with intelligent materials, such microfabricated platforms can be designed to be bioadhesive and stimuli-responsive. Apart from drug delivery devices, microfabrication technologies offer exciting opportunities to create biomimetic gastrointestinal tract models incorporating physiological cell types, flow patterns and brush-border like structures. Here we review the recent developments in this field with a focus on the applications of microfabrication in the development of oral drug delivery devices and biomimetic gastrointestinal tract models that can be used to evaluate the drug delivery efficacy.
MeSH term(s)	Administration, Oral ; Animals ; Biomimetics ; Drug Delivery Systems ; Drug Design ; Gastrointestinal Tract/metabolism ; Humans ; Microfluidics ; Microtechnology/methods ; Models, Biological ; Pharmaceutical Preparations/administration & dosage
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2011-12-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2011.11.013
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Hydrogels in regenerative medicine.

Slaughter, Brandon V / Khurshid, Shahana S / Fisher, Omar Z / Khademhosseini, Ali / Peppas, Nicholas A

Advanced materials (Deerfield Beach, Fla.)

2010 Volume 21, Issue 32-33, Page(s) 3307–3329

Abstract: Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds ... ...

Abstract	Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.
Language	English
Publishing date	2010-09-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1474949-X
ISSN	1521-4095 ; 0935-9648
ISSN (online)	1521-4095
ISSN	0935-9648
DOI	10.1002/adma.200802106
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Article: Enhanced core hydrophobicity, functionalization and cell penetration of polybasic nanomatrices.

Fisher, Omar Z / Kim, Timothy / Dietz, Stephen R / Peppas, Nicholas A

Pharmaceutical research

2008 Volume 26, Issue 1, Page(s) 51–60

Abstract: Purpose: In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling ... ...

Abstract	Purpose: In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling properties via changes in core hydrophobicity and crosslinking feed density was assessed. The nanomatrices were also evaluated in vitro as nanocarriers for targeted intracellular delivery of macromolecules. Materials and methods: Photo-emulsion polymerization was used to synthesize poly[2-(diethylamino)ethyl methacrylate-co-t-butyl methacrylate-g-poly(ethylene glycol)] (PDBP) nanomatrices. These were characterized using NMR, dynamic and electrophoretic light scattering, electron microscopy. The cytocompatibility and cellular uptake of nanomatrices was measured using the NIH/3T3 and A549 cell lines. Results: PDBP nanomatrices had a dry diameter of 40-60 nm and a hydrodynamic diameter of 70-90 nm in the collapsed state. Maximum volume swelling ratios from 6-22 were obtained depending on crosslinking feed density. Controlling the hydrophobicity of the networks allowed for control over the critical swelling pH without a significant loss in maximal volume swelling. The effect of PDBP nanomatrices on cell viability and cell membrane integrity depended on crosslinking feed density. Cell uptake and cytosolic delivery of FITC-albumin was enhanced from clathrin-targeting nanocarriers. The uptake resulted in nuclear localization of the dye in a cell type dependent fashion. Conclusions: The results of this work indicate that PDBP nanomatrices have tunable swelling properties. The networks were cytocompatible and proved to be suitable agents for intracellular delivery.
MeSH term(s)	3T3 Cells ; Amines/chemistry ; Animals ; Biocompatible Materials ; Cell Membrane/metabolism ; Cell Survival/drug effects ; Fluorescein-5-isothiocyanate ; Fluorescent Dyes ; Hydrogen-Ion Concentration ; Indicators and Reagents ; Light ; Magnetic Resonance Spectroscopy ; Methacrylates/chemistry ; Mice ; Microscopy, Electron, Scanning ; Nanoparticles/chemistry ; Nylons/chemistry ; Particle Size ; Polyethylene Glycols/chemistry ; Scattering, Radiation ; Solubility ; Surface Properties ; Water
Chemical Substances	Amines ; Biocompatible Materials ; Fluorescent Dyes ; Indicators and Reagents ; Methacrylates ; Nylons ; poly(2-(diethylamino)ethyl methacrylate) ; Water (059QF0KO0R) ; Polyethylene Glycols (3WJQ0SDW1A) ; Fluorescein-5-isothiocyanate (I223NX31W9)
Language	English
Publishing date	2008-08-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-008-9704-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Activatable interpolymer complex-superparamagnetic iron oxide nanoparticles as magnetic resonance contrast agents sensitive to oxidative stress

Yoo, Eunsoo / Amber L. Doiron / Carmen Lee / Charles T. Drinnan / David J. Beaman / Huaitzung A. Cheng / Kenneth W. Fishbein / Lauren E. Nardacci / Omar Z. Fisher / Richard G. Spencer

Elsevier B.V. Colloids and surfaces. 2017 Oct. 01, v. 158

2017

Abstract	Magnetic resonance contrast agents that can be activated in response to specific triggers hold potential as molecular biosensors that may be of great utility in non-invasive disease diagnosis. We developed an activatable agent based on superparamagnetic iron oxide nanoparticles (SPIOs) that is sensitive to oxidative stress, a factor in the pathophysiology of numerous diseases. SPIOs were coated with poly(ethylene glycol) (PEG) and complexed with poly(gallol), a synthetic tannin. Hydrogen bonding between PEG and poly(gallol) creates a complexed layer around the SPIO that decreases the interaction of solute water with the SPIO, attenuating its magnetic resonance relaxivity. The complexed interpolymer nanoparticle is in an OFF state (decreased T2 contrast), where the contrast agent has a low T2 relaxivity of 7±2mM−1s−1. In the presence of superoxides, the poly(gallol) is oxidized and the polymers decomplex, allowing solute water to again interact with the SPIO, representing an ON state (increased T2 contrast) with a T2 relaxivity of 70±10mM−1s−1. These contrast agents show promise as effective sensors for diseases characterized in part by oxidative stress such as atherosclerosis, diabetes, and cancer.
Keywords	atherosclerosis ; biosensors ; colloids ; diabetes ; disease diagnosis ; hydrogen bonding ; iron oxides ; nanoparticles ; neoplasms ; oxidative stress ; pathophysiology ; polyethylene glycol ; solutes ; superoxide anion
Language	English
Dates of publication	2017-1001
Size	p. 578-588.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2017.07.025
Database	NAL-Catalogue (AGRICOLA)

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Article: Enhanced Core Hydrophobicity, Functionalization and Cell Penetration of Polybasic Nanomatrices

Fisher, Omar Z / Kim, Timothy / Dietz, Stephen R / Peppas, Nicholas A

Pharmaceutical research. 2009 Jan., v. 26, no. 1

2009

Abstract: Purpose In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling ... ...

Abstract	Purpose In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling properties via changes in core hydrophobicity and crosslinking feed density was assessed. The nanomatrices were also evaluated in vitro as nanocarriers for targeted intracellular delivery of macromolecules. Materials and Methods Photo-emulsion polymerization was used to synthesize poly[2-(diethylamino)ethyl methacrylate-co-t-butyl methacrylate-g-poly(ethylene glycol)] (PDBP) nanomatrices. These were characterized using NMR, dynamic and electrophoretic light scattering, electron microscopy. The cytocompatibility and cellular uptake of nanomatrices was measured using the NIH/3T3 and A549 cell lines. Results PDBP nanomatrices had a dry diameter of 40-60 nm and a hydrodynamic diameter of 70-90 nm in the collapsed state. Maximum volume swelling ratios from 6-22 were obtained depending on crosslinking feed density. Controlling the hydrophobicity of the networks allowed for control over the critical swelling pH without a significant loss in maximal volume swelling. The effect of PDBP nanomatrices on cell viability and cell membrane integrity depended on crosslinking feed density. Cell uptake and cytosolic delivery of FITC-albumin was enhanced from clathrin-targeting nanocarriers. The uptake resulted in nuclear localization of the dye in a cell type dependent fashion. Conclusions The results of this work indicate that PDBP nanomatrices have tunable swelling properties. The networks were cytocompatible and proved to be suitable agents for intracellular delivery.
Language	English
Dates of publication	2009-01
Size	p. 51-60.
Publisher	Springer US
Publishing place	Boston
Document type	Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-008-9704-2
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Melanin-like hydrogels derived from gallic macromers.

Fisher, Omar Z / Larson, Benjamin L / Hill, Paulina S / Graupner, David / Nguyen-Kim, Mai-Thi / Kehr, Nermin Seda / De Cola, Luisa / Langer, Robert / Anderson, Daniel G

Advanced materials (Deerfield Beach, Fla.)

2012 Volume 24, Issue 22, Page(s) 3032–3036

MeSH term(s)	Biocompatible Materials/chemical synthesis ; Biocompatible Materials/chemistry ; Biocompatible Materials/pharmacology ; Cell Adhesion/drug effects ; Chemistry Techniques, Synthetic ; Gallic Acid/chemistry ; HeLa Cells ; Humans ; Hydrogels/chemical synthesis ; Hydrogels/chemistry ; Hydrogels/pharmacology ; Melanins/chemistry
Chemical Substances	Biocompatible Materials ; Hydrogels ; Melanins ; Gallic Acid (632XD903SP)
Language	English
Publishing date	2012-05-07
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1474949-X
ISSN	1521-4095 ; 0935-9648
ISSN (online)	1521-4095
ISSN	0935-9648
DOI	10.1002/adma.201104437
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