Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.

<h4>Background</h4>Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the dispersion and absorption of subcutaneously administered therapeutic agents. This study aimed to characterize the transient, local action of rHuPH20 in the subcutaneous (SC) space using focused biodistribut...

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Autores principales:	David W Kang, Beate Bittner, Barry J Sugarman, Monica L Zepeda, Marie A Printz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c07c075fe3a34b4e935d5c8b108458aa
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spelling	oai:doaj.org-article:c07c075fe3a34b4e935d5c8b108458aa2021-12-02T20:06:37ZDispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.1932-620310.1371/journal.pone.0254765https://doaj.org/article/c07c075fe3a34b4e935d5c8b108458aa2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254765https://doaj.org/toc/1932-6203<h4>Background</h4>Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the dispersion and absorption of subcutaneously administered therapeutic agents. This study aimed to characterize the transient, local action of rHuPH20 in the subcutaneous (SC) space using focused biodistribution and dye dispersion studies conducted in mice.<h4>Materials and methods</h4>To evaluate the biodistribution of rHuPH20, mice were intradermally administered rHuPH20 (80 U). The enzymatic activity of rHuPH20 was analyzed in the skin, lymph nodes, and plasma. Animal model sensitivity was determined by intravenous administration of rHuPH20 (80 U) to the tail vein. To evaluate local dispersion, mice received an intradermal injection of rHuPH20 followed by an intradermal injection of Trypan Blue dye at a contralateral site 45 minutes later. Dye dispersion was measured using a digital caliper.<h4>Results</h4>After intradermal rHuPH20 injection, enzymatic activity was detected within the skin near the injection site with levels decreasing rapidly after 15 minutes. There was no clear evidence of systemic exposure after administration of rHuPH20, and no discernible rHuPH20 activity was observed in lymph or plasma as a function of time after dosing. In the dye dispersion study, delivery of rHuPH20 at one site did not impact dye dispersion at a distal skin site.<h4>Conclusion</h4>These observations support the classification of rHuPH20 as a transiently active and locally acting permeation enhancer.David W KangBeate BittnerBarry J SugarmanMonica L ZepedaMarie A PrintzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254765 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David W Kang Beate Bittner Barry J Sugarman Monica L Zepeda Marie A Printz Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.
description	<h4>Background</h4>Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the dispersion and absorption of subcutaneously administered therapeutic agents. This study aimed to characterize the transient, local action of rHuPH20 in the subcutaneous (SC) space using focused biodistribution and dye dispersion studies conducted in mice.<h4>Materials and methods</h4>To evaluate the biodistribution of rHuPH20, mice were intradermally administered rHuPH20 (80 U). The enzymatic activity of rHuPH20 was analyzed in the skin, lymph nodes, and plasma. Animal model sensitivity was determined by intravenous administration of rHuPH20 (80 U) to the tail vein. To evaluate local dispersion, mice received an intradermal injection of rHuPH20 followed by an intradermal injection of Trypan Blue dye at a contralateral site 45 minutes later. Dye dispersion was measured using a digital caliper.<h4>Results</h4>After intradermal rHuPH20 injection, enzymatic activity was detected within the skin near the injection site with levels decreasing rapidly after 15 minutes. There was no clear evidence of systemic exposure after administration of rHuPH20, and no discernible rHuPH20 activity was observed in lymph or plasma as a function of time after dosing. In the dye dispersion study, delivery of rHuPH20 at one site did not impact dye dispersion at a distal skin site.<h4>Conclusion</h4>These observations support the classification of rHuPH20 as a transiently active and locally acting permeation enhancer.
format	article
author	David W Kang Beate Bittner Barry J Sugarman Monica L Zepeda Marie A Printz
author_facet	David W Kang Beate Bittner Barry J Sugarman Monica L Zepeda Marie A Printz
author_sort	David W Kang
title	Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.
title_short	Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.
title_full	Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.
title_fullStr	Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.
title_full_unstemmed	Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.
title_sort	dispersive effects and focused biodistribution of recombinant human hyaluronidase ph20: a locally acting and transiently active permeation enhancer.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c07c075fe3a34b4e935d5c8b108458aa
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Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer.

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