当前位置：
X-MOL 学术
›
Int. J. Nanomed.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Liver Targeting of Daclatasvir via Tailoring Sterically Stabilized Bilosomes: Fabrication, Comparative In Vitro/In Vivo Appraisal and Biodistribution Studies
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2021-09-17 , DOI: 10.2147/ijn.s319255 Mohamed El-Nabarawi 1 , Mohamed Nafady 2 , Shahira Elmenshawe 3 , Marwa Elkarmalawy 4 , Mahmoud Teaima 1
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2021-09-17 , DOI: 10.2147/ijn.s319255 Mohamed El-Nabarawi 1 , Mohamed Nafady 2 , Shahira Elmenshawe 3 , Marwa Elkarmalawy 4 , Mahmoud Teaima 1
Affiliation
Introduction: Hepatitis C virus (HCV) is a significant public health concern that threatens millions of individuals worldwide. Daclatasvir (DAC) is a promising direct-acting antiviral approved for treating HCV infection around the world. The goal of this study was to encapsulate DAC into novel polyethylene glycol (PEG) decorated bilosomes (PEG-BILS) to achieve enhanced drug delivery to the liver.
Methods: DAC-loaded BILS were primed by a thin film hydrating technique. The study of the impact of various formulation variables on the properties of BILS and selection of the optimal formulation was generated using Design-Expert® software. The optimum preparation was then pegylated via the incorporation of PEG-6-stearate (5% w/w, with respect to the lipid phase).
Results: The optimum PEG-BILS formulation, containing PL:SDC ratio (5:1), 5 mg cholesterol, and 30 min sonication, yielded spherical vesicles in the nanoscale (200± 15.2 nm), elevated percent of entrapment efficiency (95.5± 7.77%), and a sustained release profile of DAC with 35.11± 2.3% release. In vivo and drug distribution studies revealed an enhanced hepatocellular delivery of DAC-loaded PEG-BILS compared to DAC-unPEG-BILS and DAC suspension, where DAC-PEG-BILS achieved 1.19- and 1.54 times the AUC0– 24 of DAC-unPEG-BILS and DAC suspension, respectively. Compared with DAC-unPEG-BILS and DAC suspension, DAC-PEG-BILS delivered about 2 and 3 times higher DAC into the liver, respectively.
Conclusion: The innovative encapsulation of DAC-PEG-BILS has a great potential for liver targeting.
Keywords: antiviral drug, nanodrug delivery system, bile-based nanovesicles, Box–Behnken approach, liver targeting parameters, pharmacokinetic, bioavailability
中文翻译：
通过定制空间稳定双脂质体实现达卡他韦的肝脏靶向：制造、体外/体内比较评估和生物分布研究
简介：丙型肝炎病毒 (HCV) 是一个重大的公共卫生问题，威胁着全世界数百万人。达卡他韦 (DAC) 是一种有前途的直接作用抗病毒药物，已在世界各地被批准用于治疗 HCV 感染。本研究的目标是将 DAC 封装到新型聚乙二醇 (PEG) 修饰的胆脂质体 (PEG-BILS) 中，以增强药物向肝脏的输送。
方法：通过薄膜水合技术对负载 DAC 的 BILS 进行底涂。使用 Design-Expert ®软件进行了各种配方变量对 BILS 特性影响的研究以及最佳配方的选择。然后通过掺入 PEG-6-硬脂酸酯（5% w/w，相对于脂质相）对最佳制剂进行聚乙二醇化。
结果：最佳 PEG-BILS 配方，包含 PL:SDC 比例（5:1）、5 mg 胆固醇和 30 分钟超声处理，产生纳米级球形囊泡（200±15.2 nm），包封率提高（95.5± 7.77%），DAC 的缓释曲线为 35.11±2.3%。体内和药物分布研究表明，与 DAC-unPEG-BILS 和 DAC 悬浮液相比，负载 DAC 的 PEG-BILS 的肝细胞递送增强，其中 DAC-PEG-BILS 的 AUC 0-24是 DAC-unPEG 的 1.19 倍和 1.54 倍-分别是 BILS 和 DAC 悬架。与 DAC-unPEG-BILS 和 DAC 悬浮液相比，DAC-PEG-BILS 向肝脏输送的 DAC 分别高出约 2 倍和 3 倍。
结论： DAC-PEG-BILS 的创新封装在肝脏靶向方面具有巨大的潜力。
关键词：抗病毒药物，纳米药物递送系统，胆汁纳米囊泡，Box-Behnken方法，肝脏靶向参数，药代动力学，生物利用度
更新日期：2021-09-17
Methods: DAC-loaded BILS were primed by a thin film hydrating technique. The study of the impact of various formulation variables on the properties of BILS and selection of the optimal formulation was generated using Design-Expert® software. The optimum preparation was then pegylated via the incorporation of PEG-6-stearate (5% w/w, with respect to the lipid phase).
Results: The optimum PEG-BILS formulation, containing PL:SDC ratio (5:1), 5 mg cholesterol, and 30 min sonication, yielded spherical vesicles in the nanoscale (200± 15.2 nm), elevated percent of entrapment efficiency (95.5± 7.77%), and a sustained release profile of DAC with 35.11± 2.3% release. In vivo and drug distribution studies revealed an enhanced hepatocellular delivery of DAC-loaded PEG-BILS compared to DAC-unPEG-BILS and DAC suspension, where DAC-PEG-BILS achieved 1.19- and 1.54 times the AUC0– 24 of DAC-unPEG-BILS and DAC suspension, respectively. Compared with DAC-unPEG-BILS and DAC suspension, DAC-PEG-BILS delivered about 2 and 3 times higher DAC into the liver, respectively.
Conclusion: The innovative encapsulation of DAC-PEG-BILS has a great potential for liver targeting.
Keywords: antiviral drug, nanodrug delivery system, bile-based nanovesicles, Box–Behnken approach, liver targeting parameters, pharmacokinetic, bioavailability
中文翻译：
通过定制空间稳定双脂质体实现达卡他韦的肝脏靶向：制造、体外/体内比较评估和生物分布研究
简介：丙型肝炎病毒 (HCV) 是一个重大的公共卫生问题，威胁着全世界数百万人。达卡他韦 (DAC) 是一种有前途的直接作用抗病毒药物，已在世界各地被批准用于治疗 HCV 感染。本研究的目标是将 DAC 封装到新型聚乙二醇 (PEG) 修饰的胆脂质体 (PEG-BILS) 中，以增强药物向肝脏的输送。
方法：通过薄膜水合技术对负载 DAC 的 BILS 进行底涂。使用 Design-Expert ®软件进行了各种配方变量对 BILS 特性影响的研究以及最佳配方的选择。然后通过掺入 PEG-6-硬脂酸酯（5% w/w，相对于脂质相）对最佳制剂进行聚乙二醇化。
结果：最佳 PEG-BILS 配方，包含 PL:SDC 比例（5:1）、5 mg 胆固醇和 30 分钟超声处理，产生纳米级球形囊泡（200±15.2 nm），包封率提高（95.5± 7.77%），DAC 的缓释曲线为 35.11±2.3%。体内和药物分布研究表明，与 DAC-unPEG-BILS 和 DAC 悬浮液相比，负载 DAC 的 PEG-BILS 的肝细胞递送增强，其中 DAC-PEG-BILS 的 AUC 0-24是 DAC-unPEG 的 1.19 倍和 1.54 倍-分别是 BILS 和 DAC 悬架。与 DAC-unPEG-BILS 和 DAC 悬浮液相比，DAC-PEG-BILS 向肝脏输送的 DAC 分别高出约 2 倍和 3 倍。
结论： DAC-PEG-BILS 的创新封装在肝脏靶向方面具有巨大的潜力。
关键词：抗病毒药物，纳米药物递送系统，胆汁纳米囊泡，Box-Behnken方法，肝脏靶向参数，药代动力学，生物利用度
京公网安备 11010802027423号