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Liver Targeting of Daclatasvir via Tailoring Sterically Stabilized Bilosomes: Fabrication, Comparative In Vitro/In Vivo Appraisal and Biodistribution Studies

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 polye...

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Detalles Bibliográficos
Autores principales: El-Nabarawi, Mohamed, Nafady, Mohamed, Elmenshawe, Shahira, Elkarmalawy, Marwa, Teaima, Mahmoud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455511/
https://www.ncbi.nlm.nih.gov/pubmed/34556987
http://dx.doi.org/10.2147/IJN.S319255
Descripción
Sumario: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 AUC(0–24) 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.