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Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels

Control over of biological processes can potentially be therapeutically regulated through localized biomolecular deliveries. While implantable hydrogels can provide localized therapeutic deliveries, they do not traditionally provide the temporally complex therapeutic delivery profiles required to re...

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Autores principales: Emi, Tania, Michaud, Kendra, Orton, Emma, Santilli, Grace, Linh, Catherine, O’Connell, Meaghan, Issa, Fatima, Kennedy, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470886/
https://www.ncbi.nlm.nih.gov/pubmed/30884862
http://dx.doi.org/10.3390/molecules24061048
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author Emi, Tania
Michaud, Kendra
Orton, Emma
Santilli, Grace
Linh, Catherine
O’Connell, Meaghan
Issa, Fatima
Kennedy, Stephen
author_facet Emi, Tania
Michaud, Kendra
Orton, Emma
Santilli, Grace
Linh, Catherine
O’Connell, Meaghan
Issa, Fatima
Kennedy, Stephen
author_sort Emi, Tania
collection PubMed
description Control over of biological processes can potentially be therapeutically regulated through localized biomolecular deliveries. While implantable hydrogels can provide localized therapeutic deliveries, they do not traditionally provide the temporally complex therapeutic delivery profiles required to regulate complex biological processes. Ionically crosslinked alginate hydrogels have been shown to release encapsulated payloads in response to a remotely applied ultrasonic stimulus, thus potentially enabling more temporally complex therapeutic delivery profiles. However, thorough characterizations of how different types of therapeutic payloads are retained and ultrasonically released need to be performed. Additionally, the impact of potentially disruptive ultrasonic stimulations on hydrogel structure and temperature need to be characterized to better understand what range of ultrasonic signals can be used to trigger release. To perform these characterizations, calcium-crosslinked alginate hydrogels were loaded with various model macromolecules (dextrans), chemotherapeutics, and protein signaling factors and exposed to a variety of single-pulse and multi-pulse ultrasonic signals at various amplitudes and durations. In response to single-pulsed ultrasonic exposures, quantifications of molecular release, degree of gel erosion, and increase in hydrogel temperature revealed that the ultrasonic stimulations required for statistically significant therapeutic deliveries often eroded and heated the gels to unacceptable levels. However, multi-pulse ultrasonic exposures were shown to achieve significant amounts of therapeutic release while keeping gel erosion and temperature increase at modest levels. Finally, experiments were performed demonstrating that ultrasonic stimulation could be used to generate drug release profiles shown to have potential therapeutic benefits (e.g., pulsatile and sequential anticancer delivery profiles). This work underscores the potential of using ultrasonically responsive polymeric hydrogels for providing on-demand control over more complex therapeutic deliver profiles and enhancing drug delivery strategies in cancer therapies and beyond.
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spelling pubmed-64708862019-04-26 Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels Emi, Tania Michaud, Kendra Orton, Emma Santilli, Grace Linh, Catherine O’Connell, Meaghan Issa, Fatima Kennedy, Stephen Molecules Article Control over of biological processes can potentially be therapeutically regulated through localized biomolecular deliveries. While implantable hydrogels can provide localized therapeutic deliveries, they do not traditionally provide the temporally complex therapeutic delivery profiles required to regulate complex biological processes. Ionically crosslinked alginate hydrogels have been shown to release encapsulated payloads in response to a remotely applied ultrasonic stimulus, thus potentially enabling more temporally complex therapeutic delivery profiles. However, thorough characterizations of how different types of therapeutic payloads are retained and ultrasonically released need to be performed. Additionally, the impact of potentially disruptive ultrasonic stimulations on hydrogel structure and temperature need to be characterized to better understand what range of ultrasonic signals can be used to trigger release. To perform these characterizations, calcium-crosslinked alginate hydrogels were loaded with various model macromolecules (dextrans), chemotherapeutics, and protein signaling factors and exposed to a variety of single-pulse and multi-pulse ultrasonic signals at various amplitudes and durations. In response to single-pulsed ultrasonic exposures, quantifications of molecular release, degree of gel erosion, and increase in hydrogel temperature revealed that the ultrasonic stimulations required for statistically significant therapeutic deliveries often eroded and heated the gels to unacceptable levels. However, multi-pulse ultrasonic exposures were shown to achieve significant amounts of therapeutic release while keeping gel erosion and temperature increase at modest levels. Finally, experiments were performed demonstrating that ultrasonic stimulation could be used to generate drug release profiles shown to have potential therapeutic benefits (e.g., pulsatile and sequential anticancer delivery profiles). This work underscores the potential of using ultrasonically responsive polymeric hydrogels for providing on-demand control over more complex therapeutic deliver profiles and enhancing drug delivery strategies in cancer therapies and beyond. MDPI 2019-03-16 /pmc/articles/PMC6470886/ /pubmed/30884862 http://dx.doi.org/10.3390/molecules24061048 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Emi, Tania
Michaud, Kendra
Orton, Emma
Santilli, Grace
Linh, Catherine
O’Connell, Meaghan
Issa, Fatima
Kennedy, Stephen
Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels
title Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels
title_full Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels
title_fullStr Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels
title_full_unstemmed Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels
title_short Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels
title_sort ultrasonic generation of pulsatile and sequential therapeutic delivery profiles from calcium-crosslinked alginate hydrogels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470886/
https://www.ncbi.nlm.nih.gov/pubmed/30884862
http://dx.doi.org/10.3390/molecules24061048
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