Mohamed El-Nabarawi1, Mohamed Nafady2, Shahira Elmenshawe3, Marwa Elkarmalawy4, Mahmoud Teaima1. 1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt. 2. Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt. 3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. 4. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University of Technology and Information, Cairo, Egypt.
Abstract
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.
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.
Authors: Khalid M El-Say; Fathy I Abd-Allah; Ahmed E Lila; Abd El-Saboor A Hassan; Alaa Eldin A Kassem Journal: J Liposome Res Date: 2015-04-08 Impact factor: 3.648