A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse
The effective treatment of central nervous system (CNS) disorders such as multiple sclerosis (MS) has been challenging due to the limited ability of therapeutic agents to cross the blood–brain barrier (BBB). In this study, we investigated the potential of nanocarrier systems to deliver miR-155-antag...
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1254 |
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| author | Trideva Sastri Koduru Vishal N. Gupta Balamuralidhara Veeranna Shanmuganathan Seetharaman |
| author_facet | Trideva Sastri Koduru Vishal N. Gupta Balamuralidhara Veeranna Shanmuganathan Seetharaman |
| author_sort | Trideva Sastri Koduru |
| collection | DOAJ |
| description | The effective treatment of central nervous system (CNS) disorders such as multiple sclerosis (MS) has been challenging due to the limited ability of therapeutic agents to cross the blood–brain barrier (BBB). In this study, we investigated the potential of nanocarrier systems to deliver miR-155-antagomir-teriflunomide (TEF) dual therapy to the brain via intranasal (IN) administration to manage MS-associated neurodegeneration and demyelination. Our results showed that the combinatorial therapy of miR-155-antagomir and TEF loaded in nanostructured lipid carriers (NLCs) significantly increased brain concentration and improved targeting potential. The novelty of this study lies in the use of a combinatorial therapy approach of miR-155-antagomir and TEF loaded in NLCs. This is a significant finding, as the effective delivery of therapeutic molecules to the CNS has been a challenge in treating neurodegenerative disorders. Additionally, this study sheds light on the potential use of RNA-targeting therapies in personalized medicine, which could revolutionize the way CNS disorders are managed. Furthermore, our findings suggest that nanocarrier-loaded therapeutic agents have great potential for safe and economical delivery in treating CNS disorders. Our study provides novel insights into the effective delivery of therapeutic molecules via the IN route for managing neurodegenerative disorders. In particular, our results demonstrate the potential of delivering miRNA and TEF via the intranasal route using the NLC system. We also demonstrate that the long-term use of RNA-targeting therapies could be a promising tool in personalized medicine. Importantly, using a cuprizone-induced animal model, our study also investigated the effects of TEF-miR155-antagomir-loaded NLCs on demyelination and axonal damage. Following six weeks of treatment, the TEF-miR155-antagomir-loaded NLCs potentially lowered the demyelination and enhanced the bioavailability of the loaded therapeutic molecules. Our study is a paradigm shift in delivering miRNAs and TEF via the intranasal route and highlights the potential of this approach for managing neurodegenerative disorders. In conclusion, our study provides critical insights into the effective delivery of therapeutic molecules via the IN route for managing CNS disorders, and especially MS. Our findings have significant implications for the future development of nanocarrier-based therapies and personalized medicine. Our results provide a strong foundation for further studies and the potential to develop safe and economic therapeutics for CNS disorders. |
| first_indexed | 2024-03-11T04:38:06Z |
| format | Article |
| id | doaj.art-3f9385cf3c8f47279743cc689f49e5f8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:38:06Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj.art-3f9385cf3c8f47279743cc689f49e5f82023-11-17T20:54:54ZengMDPI AGPharmaceutics1999-49232023-04-01154125410.3390/pharmaceutics15041254A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J MouseTrideva Sastri Koduru0Vishal N. Gupta1Balamuralidhara Veeranna2Shanmuganathan Seetharaman3Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Shivarathreeshwara Nagara, Mysuru 570015, IndiaDepartment of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Shivarathreeshwara Nagara, Mysuru 570015, IndiaDepartment of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Shivarathreeshwara Nagara, Mysuru 570015, IndiaSchool of Pharmacy, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607402, IndiaThe effective treatment of central nervous system (CNS) disorders such as multiple sclerosis (MS) has been challenging due to the limited ability of therapeutic agents to cross the blood–brain barrier (BBB). In this study, we investigated the potential of nanocarrier systems to deliver miR-155-antagomir-teriflunomide (TEF) dual therapy to the brain via intranasal (IN) administration to manage MS-associated neurodegeneration and demyelination. Our results showed that the combinatorial therapy of miR-155-antagomir and TEF loaded in nanostructured lipid carriers (NLCs) significantly increased brain concentration and improved targeting potential. The novelty of this study lies in the use of a combinatorial therapy approach of miR-155-antagomir and TEF loaded in NLCs. This is a significant finding, as the effective delivery of therapeutic molecules to the CNS has been a challenge in treating neurodegenerative disorders. Additionally, this study sheds light on the potential use of RNA-targeting therapies in personalized medicine, which could revolutionize the way CNS disorders are managed. Furthermore, our findings suggest that nanocarrier-loaded therapeutic agents have great potential for safe and economical delivery in treating CNS disorders. Our study provides novel insights into the effective delivery of therapeutic molecules via the IN route for managing neurodegenerative disorders. In particular, our results demonstrate the potential of delivering miRNA and TEF via the intranasal route using the NLC system. We also demonstrate that the long-term use of RNA-targeting therapies could be a promising tool in personalized medicine. Importantly, using a cuprizone-induced animal model, our study also investigated the effects of TEF-miR155-antagomir-loaded NLCs on demyelination and axonal damage. Following six weeks of treatment, the TEF-miR155-antagomir-loaded NLCs potentially lowered the demyelination and enhanced the bioavailability of the loaded therapeutic molecules. Our study is a paradigm shift in delivering miRNAs and TEF via the intranasal route and highlights the potential of this approach for managing neurodegenerative disorders. In conclusion, our study provides critical insights into the effective delivery of therapeutic molecules via the IN route for managing CNS disorders, and especially MS. Our findings have significant implications for the future development of nanocarrier-based therapies and personalized medicine. Our results provide a strong foundation for further studies and the potential to develop safe and economic therapeutics for CNS disorders.https://www.mdpi.com/1999-4923/15/4/1254teriflunomidemiR-155-antagomirintranasal delivery routecuprizone modelmultiple sclerosis |
| spellingShingle | Trideva Sastri Koduru Vishal N. Gupta Balamuralidhara Veeranna Shanmuganathan Seetharaman A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse Pharmaceutics teriflunomide miR-155-antagomir intranasal delivery route cuprizone model multiple sclerosis |
| title | A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse |
| title_full | A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse |
| title_fullStr | A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse |
| title_full_unstemmed | A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse |
| title_short | A Dual Therapy of Nanostructured Lipid Carrier Loaded with Teriflunomide—A Dihydro-Orotate Dehydrogenase Inhibitor and an miR-155-Antagomir in Cuprizone-Induced C57BL/6J Mouse |
| title_sort | dual therapy of nanostructured lipid carrier loaded with teriflunomide a dihydro orotate dehydrogenase inhibitor and an mir 155 antagomir in cuprizone induced c57bl 6j mouse |
| topic | teriflunomide miR-155-antagomir intranasal delivery route cuprizone model multiple sclerosis |
| url | https://www.mdpi.com/1999-4923/15/4/1254 |
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