In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates

The degradation of Tetra-PEG hydrogels containing β-eliminative crosslinks has been studied in order to provide an in vitro-in vivo correlation for the use of these hydrogels in our chemically controlled drug delivery system. We measured time-dependent gel mass loss and ultrasound volume changes of...

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Main Authors: Jeff Henise, Shaun D. Fontaine, Brian R. Hearn, Samuel J. Pfaff, Eric L. Schneider, Julia Malato, Donghui Wang, Byron Hann, Gary W. Ashley, Daniel V. Santi
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:International Journal of Polymer Science
Online Access:http://dx.doi.org/10.1155/2019/9483127
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author Jeff Henise
Shaun D. Fontaine
Brian R. Hearn
Samuel J. Pfaff
Eric L. Schneider
Julia Malato
Donghui Wang
Byron Hann
Gary W. Ashley
Daniel V. Santi
author_facet Jeff Henise
Shaun D. Fontaine
Brian R. Hearn
Samuel J. Pfaff
Eric L. Schneider
Julia Malato
Donghui Wang
Byron Hann
Gary W. Ashley
Daniel V. Santi
author_sort Jeff Henise
collection DOAJ
description The degradation of Tetra-PEG hydrogels containing β-eliminative crosslinks has been studied in order to provide an in vitro-in vivo correlation for the use of these hydrogels in our chemically controlled drug delivery system. We measured time-dependent gel mass loss and ultrasound volume changes of 13 subcutaneously implanted Tetra-PEG hydrogel microspheres having degradation times ranging from ~3 to 250 days. Applying a previously developed model of Tetra-PEG hydrogel degradation, the mass changes correlate well with the in vitro rates of crosslink cleavage and hydrogel degelation. These results allow prediction of in vivo biodegradation properties of these hydrogels based on readily obtained in vitro rates, despite having degradation times that span 2 orders of magnitude. These results support the optimization of drug-releasing hydrogels and their development into long-acting therapeutics. The use of ultrasound volume measurements further provides a noninvasive technique for monitoring hydrogel degradation in the subcutaneous space.
format Article
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institution Kabale University
issn 1687-9422
1687-9430
language English
publishDate 2019-01-01
publisher Wiley
record_format Article
series International Journal of Polymer Science
spelling doaj-art-4d40cbe04a32493b86028345287c8f5e2025-08-20T03:36:21ZengWileyInternational Journal of Polymer Science1687-94221687-94302019-01-01201910.1155/2019/94831279483127In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage RatesJeff Henise0Shaun D. Fontaine1Brian R. Hearn2Samuel J. Pfaff3Eric L. Schneider4Julia Malato5Donghui Wang6Byron Hann7Gary W. Ashley8Daniel V. Santi9ProLynx, 455 Mission Bay Blvd. South, San Francisco, CA 94158, USAProLynx, 455 Mission Bay Blvd. South, San Francisco, CA 94158, USAProLynx, 455 Mission Bay Blvd. South, San Francisco, CA 94158, USAProLynx, 455 Mission Bay Blvd. South, San Francisco, CA 94158, USAProLynx, 455 Mission Bay Blvd. South, San Francisco, CA 94158, USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco, 1450 3rd St., San Francisco, CA 94158, USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco, 1450 3rd St., San Francisco, CA 94158, USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco, 1450 3rd St., San Francisco, CA 94158, USAProLynx, 455 Mission Bay Blvd. South, San Francisco, CA 94158, USAProLynx, 455 Mission Bay Blvd. South, San Francisco, CA 94158, USAThe degradation of Tetra-PEG hydrogels containing β-eliminative crosslinks has been studied in order to provide an in vitro-in vivo correlation for the use of these hydrogels in our chemically controlled drug delivery system. We measured time-dependent gel mass loss and ultrasound volume changes of 13 subcutaneously implanted Tetra-PEG hydrogel microspheres having degradation times ranging from ~3 to 250 days. Applying a previously developed model of Tetra-PEG hydrogel degradation, the mass changes correlate well with the in vitro rates of crosslink cleavage and hydrogel degelation. These results allow prediction of in vivo biodegradation properties of these hydrogels based on readily obtained in vitro rates, despite having degradation times that span 2 orders of magnitude. These results support the optimization of drug-releasing hydrogels and their development into long-acting therapeutics. The use of ultrasound volume measurements further provides a noninvasive technique for monitoring hydrogel degradation in the subcutaneous space.http://dx.doi.org/10.1155/2019/9483127
spellingShingle Jeff Henise
Shaun D. Fontaine
Brian R. Hearn
Samuel J. Pfaff
Eric L. Schneider
Julia Malato
Donghui Wang
Byron Hann
Gary W. Ashley
Daniel V. Santi
In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates
International Journal of Polymer Science
title In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates
title_full In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates
title_fullStr In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates
title_full_unstemmed In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates
title_short In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates
title_sort in vitro in vivo correlation for the degradation of tetra peg hydrogel microspheres with tunable β eliminative crosslink cleavage rates
url http://dx.doi.org/10.1155/2019/9483127
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