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Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the treatment of inflammatory pain, such as in osteoarthritis. Ketorolac tromethamine is considered to be an NSAID with strong anti-inflammatory and analgesic potency, however, traditional applications, such as oral administratio...

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Autores principales: Hou, Zhiyuan, Wen, Qiang, Zhou, Wenhu, Yan, Peng, Zhang, Hailong, Ding, Jinsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10223623/
https://www.ncbi.nlm.nih.gov/pubmed/37242647
http://dx.doi.org/10.3390/pharmaceutics15051405
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author Hou, Zhiyuan
Wen, Qiang
Zhou, Wenhu
Yan, Peng
Zhang, Hailong
Ding, Jinsong
author_facet Hou, Zhiyuan
Wen, Qiang
Zhou, Wenhu
Yan, Peng
Zhang, Hailong
Ding, Jinsong
author_sort Hou, Zhiyuan
collection PubMed
description Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the treatment of inflammatory pain, such as in osteoarthritis. Ketorolac tromethamine is considered to be an NSAID with strong anti-inflammatory and analgesic potency, however, traditional applications, such as oral administration and injections, often induce high systemic exposure, leading to adverse events such as gastric ulceration and bleeding. To address this key limitation, herein we designed and fabricated a topical delivery system for ketorolac tromethamine via cataplasm, which is based on a three-dimensional mesh structure formed by the cross-linking of dihydroxyaluminum aminoacetate (DAAA) and sodium polyacrylate. The viscoelasticity of the cataplasm was characterized by rheological methods and exhibited a “gel-like” elastic property. The release behavior showed a Higuchi model characteristic with a dose dependence. To enhance the skin permeation, permeation enhancers were added and screened utilizing ex vivo pig skin, in which 1,2-propanediol was found to have the optimal permeation-promoting effect. The cataplasm was further applied to a rat carrageenan-induced inflammatory pain model, which showed comparable anti-inflammatory and analgesic effects with oral administration. Finally, the biosafety of the cataplasm was tested in healthy human volunteers, and reduced side effects were achieved as compared to the tablet formulation, which can be ascribed to less systemic drug exposure and lower blood drug concentrations. Therefore, the constructed cataplasm can reduce the risk of adverse events while maintaining efficacy, thus serving as a better alternative for the treatment of inflammatory pain, including osteoarthritis.
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spelling pubmed-102236232023-05-28 Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy Hou, Zhiyuan Wen, Qiang Zhou, Wenhu Yan, Peng Zhang, Hailong Ding, Jinsong Pharmaceutics Article Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the treatment of inflammatory pain, such as in osteoarthritis. Ketorolac tromethamine is considered to be an NSAID with strong anti-inflammatory and analgesic potency, however, traditional applications, such as oral administration and injections, often induce high systemic exposure, leading to adverse events such as gastric ulceration and bleeding. To address this key limitation, herein we designed and fabricated a topical delivery system for ketorolac tromethamine via cataplasm, which is based on a three-dimensional mesh structure formed by the cross-linking of dihydroxyaluminum aminoacetate (DAAA) and sodium polyacrylate. The viscoelasticity of the cataplasm was characterized by rheological methods and exhibited a “gel-like” elastic property. The release behavior showed a Higuchi model characteristic with a dose dependence. To enhance the skin permeation, permeation enhancers were added and screened utilizing ex vivo pig skin, in which 1,2-propanediol was found to have the optimal permeation-promoting effect. The cataplasm was further applied to a rat carrageenan-induced inflammatory pain model, which showed comparable anti-inflammatory and analgesic effects with oral administration. Finally, the biosafety of the cataplasm was tested in healthy human volunteers, and reduced side effects were achieved as compared to the tablet formulation, which can be ascribed to less systemic drug exposure and lower blood drug concentrations. Therefore, the constructed cataplasm can reduce the risk of adverse events while maintaining efficacy, thus serving as a better alternative for the treatment of inflammatory pain, including osteoarthritis. MDPI 2023-05-04 /pmc/articles/PMC10223623/ /pubmed/37242647 http://dx.doi.org/10.3390/pharmaceutics15051405 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hou, Zhiyuan
Wen, Qiang
Zhou, Wenhu
Yan, Peng
Zhang, Hailong
Ding, Jinsong
Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy
title Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy
title_full Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy
title_fullStr Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy
title_full_unstemmed Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy
title_short Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy
title_sort topical delivery of ketorolac tromethamine via cataplasm for inflammatory pain therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10223623/
https://www.ncbi.nlm.nih.gov/pubmed/37242647
http://dx.doi.org/10.3390/pharmaceutics15051405
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