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. 2021 Sep 17:16:6413-6426.
doi: 10.2147/IJN.S319255. eCollection 2021.

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

Mohamed El-Nabarawi  1 , Mohamed Nafady  2 , Shahira Elmenshawe  3 , Marwa Elkarmalawy  4 , Mahmoud Teaima  1
Affiliations

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

Mohamed El-Nabarawi et al. Int J Nanomedicine. .

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.

Keywords: Box–Behnken approach; antiviral drug; bile-based nanovesicles; bioavailability; liver targeting parameters; nanodrug delivery system; pharmacokinetic.

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Conflict of interest statement

The authors state no conflicts of interest. The content and the writing of this article are the responsibility of the authors only.

Figures

Figure 1
Figure 1
Response surface plots for the effect of ratio of PL:SDC (A), CH amount (B), and sonication time (C) on (Y1) particle size, (Y2) EE%, and (Y3) % drug release.
Figure 2
Figure 2
Transmission electron micrograph of unPEG-BILS (A) and PEG-BILS (B) optimum formulation.
Figure 3
Figure 3
Mean plasma concentration–time curves of DAC in rats after oral administration of DAC suspension, DAC-unPEG-BILS, and DAC-PEG-BILS at a dose equivalent to 60 mg/kg of DAC (n=6).
See this image and copyright information in PMC

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