Long-Circulation and Brain Targeted Isoliquiritigenin Micelle Nanoparticles: Formation, Characterization, Tissue Distribution, Pharmacokinetics and Effects for Ischemic Stroke
| Autor: | Weitong Song, Lu Bai, Yuya Yang, Yongchao Wang, Pingxiang Xu, Yuming Zhao, Xuelin Zhou, Xiaorong Li, Ming Xue |
|---|---|
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | International journal of nanomedicine. 17 |
| ISSN: | 1178-2013 8610-8395 |
| Popis: | Weitong Song,1 Lu Bai,1 Yuya Yang,1 Yongchao Wang,2 Pingxiang Xu,1,3 Yuming Zhao,1 Xuelin Zhou,1,3 Xiaorong Li,1,3 Ming Xue1,3 1Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, Peopleâs Republic of China; 2CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, Peopleâs Republic of China; 3Beijing Laboratory for Biomedical Detection Technology and Instrument, Beijing, Peopleâs Republic of ChinaCorrespondence: Ming Xue, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Youanmen, Beijing, 100069, Peopleâs Republic of China, Tel +8610-83950416, Fax +8610-83911520, Email xuem@ccmu.edu.cnPurpose: We designed a novel isoliquiritigenin (ISL) loaded micelle prepared with DSPE-PEG2000 as the drug carrier modified with the brain-targeting polypeptide angiopep-2 to improve the poor water solubility and low bioavailability of ISL for the treatment of acute ischemic stroke.Methods: Thin film evaporation was used to synthesize the ISL micelles (ISL-M) modified with angiopep-2 as the brain targeted ligands. The morphology of the micelles was observed by the TEM. The particle size and zeta potential were measured via the nanometer particle size analyzer. The drug loading, encapsulation and in vitro release rates of micelles were detected by the HPLC. The UPLC-ESI-MS/MS methods were used to measure the ISL concentrations of ISL in plasma and main tissues after intravenous administration, and compared the pharmacokinetics and tissue distributions between ISL and ISL-M. In the MCAO mice model, the protective effects of ISL and ISL-M were confirmed via the behavioral and molecular biology experiments.Results: The results showed that the drug loading of ISL-M was 7.63 ± 2.62%, the encapsulation efficiency was 68.17 ± 6.23%, the particle size was 40.87 ± 4.82 nm, and the zeta potential was â 34.23 ± 3.35 mV. The in vitro release experiments showed that ISL-M had good sustained-release effect and pH sensitivity. Compared with ISL monomers, the ISL-M could significantly prolong the in vivo circulation time of ISL and enhance the accumulation in the brain tissues. The ISL-M could ameliorate the brain injury induced by the MCAO mice via inhibition of cellular autophagy and neuronal apoptosis. There were no the cellular structural damages and other adverse effects for ISL-M on the main tissues and organs.Conclusion: The ISL-M could serve as a promising and ideal drug candidate for the clinical application of ISL in the treatment of acute ischemic stroke.Keywords: isoliquiritigenin, micelle, brain distribution, pharmacokinetics, ischemic stroke, MCAO |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|