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"parsedDate": "2009-12",
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"itemType": "journalArticle",
"title": "Electrically assisted delivery of macromolecules into the corneal epithelium",
"creators": [
{
"creatorType": "author",
"firstName": "Jinsong",
"lastName": "Hao"
},
{
"creatorType": "author",
"firstName": "S Kevin",
"lastName": "Li"
},
{
"creatorType": "author",
"firstName": "Chia-Yang",
"lastName": "Liu"
},
{
"creatorType": "author",
"firstName": "Winston W Y",
"lastName": "Kao"
}
],
"abstractNote": "Electrically assisted delivery is noninvasive and has been investigated in a number of ocular drug delivery studies. The objectives of this study were to examine the feasibility of electrically assisted delivery of macromolecules such as small interfering RNA (siRNA) into the corneal epithelium, to optimize the iontophoresis and electroporation methods, and to study the mechanisms of corneal iontophoresis for macromolecules. Anodal and cathodal iontophoresis, electroporation and their combinations were the methods examined with mice in vivo. Cyanine 3 (Cy3)-labeled glyceraldehyde-3-phosphate dehydrogenase (GAPDH) siRNA and fluorescein isothiocyanate (FITC)-labeled dextran of different molecular weights (4-70 kDa) were the macromolecules studied. Microscopy and histology after cryostat sectioning were used to analyze and compare the delivery of the macromolecules to the cornea. Iontophoresis was effective in delivering siRNA and dextran up to 70 kDa into the cornea. The electroporation method studied was less effective than that of iontophoresis. Although both iontophoresis and electroporation alone can deliver the macromolecules into the cornea, these methods alone were not as effective as the combination of iontophoresis and electroporation (iontophoresis followed by electroporation). The significant enhancement of dextran delivery in anodal iontophoresis suggests that electroosmosis can be a significant flux-enhancing mechanism during corneal iontophoresis. These results illustrate the feasibility of electrically assisted delivery of macromolecules such as siRNA into the cornea.",
"publicationTitle": "Experimental Eye Research",
"publisher": "",
"place": "",
"date": "Dec 2009",
"volume": "89",
"issue": "6",
"section": "",
"partNumber": "",
"partTitle": "",
"pages": "934-941",
"series": "",
"seriesTitle": "",
"seriesText": "",
"journalAbbreviation": "Exp. Eye Res",
"DOI": "10.1016/j.exer.2009.08.001",
"citationKey": "",
"url": "http://www.ncbi.nlm.nih.gov/pubmed/19682448",
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"extra": "PMID: 19682448",
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"type": 1
},
{
"tag": "Dextrans",
"type": 1
},
{
"tag": "Drug Delivery Systems",
"type": 1
},
{
"tag": "Electroporation",
"type": 1
},
{
"tag": "Epithelium, Corneal",
"type": 1
},
{
"tag": "Feasibility Studies",
"type": 1
},
{
"tag": "Gene Transfer Techniques",
"type": 1
},
{
"tag": "Glyceraldehyde-3-Phosphate Dehydrogenases",
"type": 1
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{
"tag": "Iontophoresis",
"type": 1
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{
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"type": 1
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{
"tag": "Male",
"type": 1
},
{
"tag": "Mice",
"type": 1
},
{
"tag": "Mice, Inbred C57BL",
"type": 1
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{
"tag": "RNA, Small Interfering",
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"parsedDate": "2009-10",
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"version": 1,
"itemType": "journalArticle",
"title": "The influence of porosity changes in human epidermal membrane during iontophoresis on the permeability enhancement of a model peptide",
"creators": [
{
"creatorType": "author",
"firstName": "Hugh D C",
"lastName": "Smyth"
},
{
"creatorType": "author",
"firstName": "Gordon",
"lastName": "Becket"
},
{
"creatorType": "author",
"firstName": "Samir",
"lastName": "Mehta"
}
],
"abstractNote": "PURPOSE We tested the hypothesis that the increases in the porosity of the skin during iontophoresis would not significantly increase the transport of peptides due to the small size of electrically induced pores. To investigate this mechanistically, we used human epidermal membrane under constant voltage conditions, applying the Nernst-Planck equation to the transport of a small ionic solute, tetraethylammonium bromide (TEAB), and a model peptide, luteinizing hormone releasing hormone. METHODS Steady-state flux of the drugs was determined under passive conditions and also during iontophoresis using constant DC voltages applied across side-by-side diffusion cells. Electrical conductance measurements were used to monitor the porosity changes that occur during electrical field application. RESULTS Porosity increases observed in the membrane substantially increased the permeability enhancement of the small ionic solute TEAB. The permeability enhancement was well described by Nernst-Planck model predictions after porosity changes in the membrane were taken into account. Enhancement of luteinizing hormone releasing hormone under identical conditions was much less than TEAB. The porosity increases induced by iontophoresis had little or no effect on the permeability enhancement of the larger molecule. CONCLUSIONS These findings closely parallel those reports that have found electrically induced pores to be significantly smaller than preexisting pores in the human epidermal membrane. The data obtained also support the view that iontophoresis-induced pores, alone, may provide limited benefit for macromolecule transport across the skin.",
"publicationTitle": "Drug Development and Industrial Pharmacy",
"publisher": "",
"place": "",
"date": "Oct 2009",
"volume": "35",
"issue": "10",
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"partNumber": "",
"partTitle": "",
"pages": "1201-1209",
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"seriesTitle": "",
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"journalAbbreviation": "Drug Dev Ind Pharm",
"DOI": "10.1080/03639040902865673",
"citationKey": "",
"url": "http://www.ncbi.nlm.nih.gov/pubmed/19555248",
"accessDate": "2011-05-11T09:15:00Z",
"PMID": "",
"PMCID": "",
"ISSN": "1520-5762",
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"language": "",
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"callNumber": "",
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"extra": "PMID: 19555248",
"tags": [
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"type": 1
},
{
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"type": 1
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{
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"type": 1
},
{
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{
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{
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{
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"type": 1
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{
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"title": "The graft content of hyaluronan is increased during xenograft rejection - Lorant - 2004 - Xenotransplantation - Wiley Online Library",
"accessDate": "2011-03-11T03:16:48Z",
"url": "http://onlinelibrary.wiley.com/doi/10.1111/j.1399-3089.2004.00132.x/pdf",
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"title": "The graft content of hyaluronan is increased during xenograft rejection",
"creators": [
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"firstName": "Tomas",
"lastName": "Lorant"
},
{
"creatorType": "author",
"firstName": "Gunnar",
"lastName": "Tufveson"
},
{
"creatorType": "author",
"firstName": "Cecilia",
"lastName": "Johnsson"
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],
"abstractNote": "Hyaluronan, a macromolecule with strong water binding capacity, is associated with interstitial oedema during rejection of allogeneic transplants. However, the involvement of hyaluronan during xenograft rejection has previously not been investigated. The aims of this study were to characterize hyaluronan content and distribution during rejection of concordant mouse-to-rat cardiac xenografts, and to explore the effects of hyaluronidase (HAse) on xenograft survival.\nGraft recipients were treated with 15-deoxyspergualin (DSG) or both HAse and DSG. Grafts were removed on day 5 from some of the animals to analyse hyaluronan and water content, while other animals were used to investigate graft survival. The hyaluronan content was measured by a radiometric assay and the distribution was analysed by histochemical staining.\nIn xenografts undergoing rejection (the DSG group) there was a strong increase of the hyaluronan [555 +/- 93 microg/g dry weight (dw)] and water (82.7 +/- 0.4%) contents compared with normal mouse heart tissue (166 +/- 10 microg/g dw; P < 0.01 and 78.6 +/- 0.5%; P < 0.001, respectively). The combined use of HAse and DSG reduced the accumulation of hyaluronan (284 +/- 43 microg/g dw; P < 0.05 vs. DSG) but did not affect the average water content. The average graft survival time did not differ between the groups; however, three grafts in the HAse + DSG-treatment group survived much longer than the longest-surviving grafts in the DSG group.\nThese data suggest that the graft content of hyaluronan considerably increases during xenograft rejection. HAse effectively reduces this accumulation, but does not affect the average water content.",
"publicationTitle": "Xenotransplantation",
"publisher": "",
"place": "",
"date": "May 2004",
"volume": "11",
"issue": "3",
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"partNumber": "",
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"pages": "269-275",
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"journalAbbreviation": "Xenotransplantation",
"DOI": "10.1111/j.1399-3089.2004.00132.x",
"citationKey": "",
"url": "http://www.ncbi.nlm.nih.gov/pubmed/15099207",
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"extra": "PMID: 15099207",
"tags": [
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"type": 1
},
{
"tag": "Graft Rejection",
"type": 1
},
{
"tag": "Heart Transplantation",
"type": 1
},
{
"tag": "Hyaluronic Acid",
"type": 1
},
{
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{
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{
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{
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"lastName": "Lumare"
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"abstractNote": "Desmoid and fibroma tumours are characterized by cell proliferation, glycosaminoglycan and collagen fibre accumulation, high levels of transforming growth factor beta(1) (TGFbeta(1)) and different patterns of tissue infiltration. TGFbeta(1) is related to extracellular matrix (ECM) composition which, in turn, regulates cell functions and cell migration. In this study we report changes in cell proliferation, glycosaminoglycan (GAG) and collagen synthesis, TGFbeta(1) mRNA expression and fibronectin levels in normal, desmoid and fibroma fibroblast cultures before and after TGFbeta(1) stimulation. Our data showed cell proliferation, GAG and collagen synthesis, transforming growth factor beta(1) mRNA expression and fibronectin levels were significantly higher in desmoid than in fibroma cultures. TGFbeta(1) treatment had no effect on cell proliferation, but increased TGFbeta(1) mRNA expression, GAG, fibronectin and collagen synthesis in desmoid and fibroma fibroblasts. Its effects were more marked in desmoid cells. Fibronectin favours cell migration, while changes in GAG composition alter cell behaviour and ECM organization. In conclusion our data suggest that the different patterns of infiltration in desmoid and fibroma tumours are due to changes in ECM components and cell-ECM interactions which can be ascribed to altered TGFbeta(1) mRNA expression and TGFbeta(1) activity.",
"publicationTitle": "Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie",
"publisher": "",
"place": "",
"date": "2007 Feb-Apr",
"volume": "61",
"issue": "2-3",
"section": "",
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"partTitle": "",
"pages": "131-136",
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"journalAbbreviation": "Biomed. Pharmacother",
"DOI": "10.1016/j.biopha.2006.09.011",
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"abstractNote": "Microcystin-LR (MCLR) is the most toxic and most frequently encountered hepatotoxin in the aquatic environment. This study investigated the protein profiles of zebrafish (Danio rerio) livers chronically exposed to MCLR concentrations (2 or 20 microg/l) using the proteomic approach as well as cell ultrastructure, protein phosphatase (PP) activity, protein phosphatase 2A (PP2A) abundance, and toxin content analysis of the hepatic tissue. The results showed that, after 30-day exposure, the presence of MCLR strikingly enhanced toxin accumulation and the PP activity in zebrafish livers. However, the PP2A amounts were independent of toxin treatments. MCLR caused a noticeable damage to liver ultrastructure, a widespread swelling in the rough endoplasmatic reticulum and mitochondria was observed in the MCLR-exposed hepatocytes, and a honeycomb-like structure was formed in the treated nucleoli. Comparison of two-dimensional electrophoresis (2-DE) protein profiles of MCLR-exposed and nonexposed zebrafish livers revealed that the abundance of 22 proteins, measured by 2-DE, was remarkably altered in response to toxin exposure. These proteins were involved in cytoskeleton assembly, macromolecule metabolism, oxidative stress, and signal transduction, indicating that MCLR toxicity in fish liver is complex and diverse. Thus, proteomics provides a new insight into MCLR toxicity, that chronic toxicity of MCLR is different from acute toxicity, and we speculate that the reactive oxygen species pathway might be the main toxic pathway instead of the PP one. Moreover, even a low concentration of MCLR in water could significantly interrupt cellular processes, and more care should be taken in determining the criterion for MCLR content in drinking water.",
"publicationTitle": "Toxicological Sciences: An Official Journal of the Society of Toxicology",
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"publicationTitle": "The Journal of Investigative Dermatology",
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"title": "Iontophoresis-Facilitated Delivery of Prednisolone through Throat Skin to the Trachea After Topical Application of its Succinate Salt",
"creators": [
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"creatorType": "author",
"firstName": "Hiroshi",
"lastName": "Ishii"
},
{
"creatorType": "author",
"firstName": "Tsukasa",
"lastName": "Suzuki"
},
{
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"firstName": "Hiroaki",
"lastName": "Todo"
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{
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"firstName": "Mitsuhiro",
"lastName": "Kamimura"
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{
"creatorType": "author",
"firstName": "Kenji",
"lastName": "Sugibayashi"
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"abstractNote": "PURPOSE: The possibility of direct delivery of steroids through the skin to the trachea and the effect of iontophoresis on delivery efficacy were evaluated after the application of an ionic steroidal prodrug, prednisolone sodium succinate (PS-Na), to the throat skin. METHODS: Fluorescein sodium salt (FL-Na) and PS-Na were applied as model compounds at a concentration of 1% in pH 7.4 phosphate-buffered saline to the throat skin of hairless rats, and constant current-cathodal iontophoresis (0.4 mA/cm(2)) was performed for 8 or 10 h. RESULTS: In vitro permeation experiment involving cathodal iontophoresis through excised hairless rat abdominal skin revealed 30- and 10-times higher levels of skin permeation of PS and its active drug, prednisolone (P), than those induced without iontophoresis. In vivo iontophoresis treatment of the rat's throat skin produced 2.6-, 1.6- and 12-times higher FL, PS and P concentrations, respectively, in the trachea than those observed without iontophoresis. CONCLUSION: The present results suggest the usefulness of topical application of the ionic steroidal prodrugs onto throat skin followed by iontophoresis treatment for directly delivering the steroid to the trachea.",
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