Anti-edema and antioxidant combination therapy for ischemic stroke via glyburide-loaded betulinic acid nanoparticles
| Autor: | Kevin N. Sheth, Haitian Zhao, Yiyun Huang, Jun Liu, Pan Zou, Ann T. Chen, Zeming Chen, Yang Xin, W. Taylor Kimberly, Jonathan Avery, Jiangbing Zhou, Daniel Holden, Fuyao Liu, Keunpoong Lim, Songye Li, Chao Ma, Richard E. Carson, Shenqi Zhang, Gang Deng, J. Marc Simard, Qianxue Chen, Fengyi Du |
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| Rok vydání: | 2019 |
| Předmět: |
Male
antioxidant Antioxidant Combination therapy medicine.medical_treatment Drug delivery to the brain Medicine (miscellaneous) Brain Edema Pharmacology Antioxidants combination therapy Rats Sprague-Dawley Mice 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Pharmacotherapy betulinic acid Positron Emission Tomography Computed Tomography Edema Betulinic acid Glyburide ischemic stroke Animals Humans Medicine Pharmacology Toxicology and Pharmaceutics (miscellaneous) Stroke 030304 developmental biology 0303 health sciences business.industry Eucommiaceae medicine.disease Triterpenes Rats 3. Good health Mice Inbred C57BL chemistry Ischemic stroke Nanoparticles Drug Therapy Combination medicine.symptom Pentacyclic Triterpenes business 030217 neurology & neurosurgery Drugs Chinese Herbal Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.35791 |
| Popis: | Stroke is a deadly disease without effective pharmacotherapies, which is due to two major reasons. First, most therapeutics cannot efficiently penetrate the brain. Second, single agent pharmacotherapy may be insufficient and effective treatment of stroke requires targeting multiple complementary targets. Here, we set to develop single component, multifunctional nanoparticles (NPs) for targeted delivery of glyburide to the brain for stroke treatment. Methods: To characterize the brain penetrability, we radiolabeled glyburide, intravenously administered it to stroke- bearing mice, and determined its accumulation in the brain using positron emission tomography-computed tomography (PET/CT). To identify functional nanomaterials to improve drug delivery to the brain, we developed a chemical extraction approach and tested it for isolation of nanomaterials from E. ulmoides, a medicinal herb. To assess the therapeutic benefits, we synthesized glyburide-loaded NPs and evaluated them in stroke- bearing mice. Results: We found that glyburide has a limited ability to penetrate the ischemic brain. We identified betulinic acid (BA) capable of forming NPs, which, after intravenous administration, efficiently penetrate the brain and significantly reduce ischemia-induced infarction as an antioxidant agent. We demonstrated that BA NPs enhance delivery of glyburide, leading to therapeutic benefits significantly greater than those achieved by either glyburide or BA NPs. Conclusion: This study suggests a new direction to identify functional nanomaterials and a simple approach to achieving anti-edema and antioxidant combination therapy. The resulting glyburide- loaded BA NPs may be translated into clinical applications to improve clinical management of stroke. |
| Databáze: | OpenAIRE |
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