Lipid polymer hybrid nanocarriers as a combinatory platform for different anti-SARS-CoV-2 drugs supported by computational studies

Hend Mohamed Abdel-Bar; Inas A Abdallah; Marwa A A Fayed; Yassmin Moatasim; Ahmed Mostafa; Mohammed Farrag El-Behairy; Hanan Elimam; Yaseen A M M Elshaier; Khaled A M Abouzid

doi:10.1039/d1ra04576h

Lipid polymer hybrid nanocarriers as a combinatory platform for different anti-SARS-CoV-2 drugs supported by computational studies

RSC Adv. 2021 Aug 27;11(46):28876-28891. doi: 10.1039/d1ra04576h. eCollection 2021 Aug 23.

Authors

Hend Mohamed Abdel-Bar¹, Inas A Abdallah², Marwa A A Fayed³, Yassmin Moatasim⁴, Ahmed Mostafa⁴, Mohammed Farrag El-Behairy⁵, Hanan Elimam⁶, Yaseen A M M Elshaier⁵, Khaled A M Abouzid⁵

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, University of Sadat City Menoufia 32897 Egypt.
² Department of Analytical Chemistry, Faculty of Pharmacy, University of Sadat City Menoufia 32897 Egypt.
³ Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City Menoufia 32897 Egypt.
⁴ Center of Scientific Excellence for Influenza Viruses, National Research Centre Giza 12622 Egypt.
⁵ Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City Menoufia 32897 Egypt [email protected] [email protected].
⁶ Department of Biochemistry, Faculty of Pharmacy, University of Sadat City Menoufia 32897 Egypt.

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has demonstrated the potential of emergent pathogens to severely damage public health and global economies. As a consequence of the pandemic, millions of people have been forced into self-isolation, which has negatively affected the global economy. More efforts are needed to find new innovative approaches that could fundamentally change our understanding and management of this disaster. Herein, lipid polymer hybrid nanoparticles (LPH NPs) were utilized as a platform for the delivery of azithromycin or niclosamide in combination with piroxicam. The obtained systems were successfully loaded with both azithromycin and piroxicam (LPH_Azi-Pir) with entrapment efficiencies (EE%) of 74.23 ± 8.14% and 51.52 ± 5.45%, respectively, or niclosamide and piroxicam (LPH_Nic-Pir) with respective EE% of 85.14 ± 3.47% and 48.75 ± 4.77%. The prepared LPH NPs had a core-shell nanostructure with particle size ≈ 125 nm and zeta potential ≈ -16.5 irrespective of drug payload. A dose-dependent cellular uptake of both LPH NPs was observed in human lung fibroblast cells. An enhanced in vitro antiviral efficacy of both LPH_Azi-Pir and LPH_Nic-Pir was obtained over the mixed solution of the drugs. The LPH NPs of azithromycin or niclosamide with piroxicam displyed a promising capability to hinder the replication of SARS-CoV-2, with IC₅₀ of 3.16 and 1.86 μM, respectively. These results provide a rationale for further in vivo pharmacological as well as toxicological studies to evaluate the potential activity of these drugs to combat the COVID-19 outbreak, especially the concept of combination therapy. Additionally, the molecular docking of macrolide bioactive compounds against papain-like protease (PDB ID:6wuu) was achieved. A ligand-based study, especially rapid overlay chemical structure (ROCS), was also examined to identify the general pharmacophoric features of these compounds and their similarity to reported anti-SARS-CoV-2 drugs. Molecular dynamic simulation was also implemented.