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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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1405 |
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| author | Zhiyuan Hou Qiang Wen Wenhu Zhou Peng Yan Hailong Zhang Jinsong Ding |
| author_facet | Zhiyuan Hou Qiang Wen Wenhu Zhou Peng Yan Hailong Zhang Jinsong Ding |
| author_sort | Zhiyuan Hou |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T03:24:51Z |
| format | Article |
| id | doaj.art-e2abebf7abf64a32937322b339cdcbee |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:51Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e2abebf7abf64a32937322b339cdcbee2023-11-18T02:51:07ZengMDPI AGPharmaceutics1999-49232023-05-01155140510.3390/pharmaceutics15051405Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain TherapyZhiyuan Hou0Qiang Wen1Wenhu Zhou2Peng Yan3Hailong Zhang4Jinsong Ding5Xiangya School of Pharmaceutical Science, Central South University, Changsha 410006, ChinaXiangya School of Pharmaceutical Science, Central South University, Changsha 410006, ChinaXiangya School of Pharmaceutical Science, Central South University, Changsha 410006, ChinaXiangya School of Pharmaceutical Science, Central South University, Changsha 410006, ChinaXiangya School of Pharmaceutical Science, Central South University, Changsha 410006, ChinaXiangya School of Pharmaceutical Science, Central South University, Changsha 410006, ChinaNonsteroidal 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.https://www.mdpi.com/1999-4923/15/5/1405ketorolac tromethaminetopical drug delivery systemcataplasmanti-inflammatoryanalgesic |
| spellingShingle | Zhiyuan Hou Qiang Wen Wenhu Zhou Peng Yan Hailong Zhang Jinsong Ding Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy Pharmaceutics ketorolac tromethamine topical drug delivery system cataplasm anti-inflammatory analgesic |
| 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 | ketorolac tromethamine topical drug delivery system cataplasm anti-inflammatory analgesic |
| url | https://www.mdpi.com/1999-4923/15/5/1405 |
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