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. 2021 Jan 5:592:120028.
doi: 10.1016/j.ijpharm.2020.120028. Epub 2020 Nov 7.

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19

Hesham Refaat  1 , Fatma M Mady  2 , Hatem A Sarhan  2 , Heba S Rateb  3 , Eman Alaaeldin  4
Affiliations

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19

Hesham Refaat et al. Int J Pharm. .

Abstract

The present work aimed to develop an optimized liposomal formulation for enhancing the anti-viral activity of propolis against COVID-19. Docking studies were performed for certain components of Egyptian Propolis using Avigan, Hydroxychloroquine and Remdesivir as standard antivirals against both COVID-19 3CL-protease and S1 spike protein. Response surface methodology and modified injection method were implemented to maximize the entrapment efficiency and release of the liposomal formulation. The optimized formulation parameters were as follow: LMC of 60 mM, CH% of 20% and DL of 5 mg/ml. At those values the E.E% and released % were 70.112% and 81.801%, respectively with nanosized particles (117 ± 11 nm). Docking studies revealed that Rutin and Caffeic acid phenethyl ester showed the highest affinity to both targets. Results showed a significant inhibitory effect of the optimized liposomal formula of Propolis against COVID-3CL protease (IC50 = 1.183 ± 0.06) compared with the Egyptian propolis extract (IC50 = 2.452 ± 0.11), P < 0.001. Interestingly, the inhibition of viral replication of COVID-19 determined by RT_PCR has been significantly enhanced via encapsulation of propolis extract within the liposomal formulation (P < 0.0001) and was comparable to the viral inhibitory effect of the potent antiviral (remdesivir). These findings identified the potential of propolis liposomes as a promising treatment approach against COVID-19.

Keywords: 3CL-protease; COVID-19; Liposomes; Propolis; RT-PCR; Spike protein.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
3D-plots for docking of A) N3, native ligand; B) Avigan; c) Hydroxychloroquine; D) Rutin; E) Caffeic acid phenethyl ester and F) Quercetin G) Remdesivir in the active site of COVID-19 3CL-protease, (pdb ID: 6LU7). H) 3D-plot for comparison pose docking of native ligand, 2 standards and the most active 3 components of Egyptian propolis.
Fig. 2
Fig. 2
3D-plots for docking of A) Avigan; B) Hydroxychloroquine; C) Rutin; D) Caffeic acid phenethyl ester E) Pinobanksin and F) Quercetin G) Remdesivir in the active site of COVID-19 S1 spike protein, (pdb ID: 7BZ5). H) represents 3D-plot for comparison pose docking of 2 standards and the most active 4 components of Egyptian propolis.
Fig. 3
Fig. 3
predicted vs actual plot of the predicted model of the E.E %
Fig. 4
Fig. 4
Effect of LMC, CH% and DL on E.E % of PP-Lip.
Fig. 5
Fig. 5
Interactive effect of LMC and DL on E.E %
Fig. 6
Fig. 6
3D surface plot of E.E % model.
Fig. 7
Fig. 7
Predicted vs actual plot of suggested model of release %.
Fig. 8
Fig. 8
Effect of LMC, CH% and DL on release % of PP-Lip.
Fig. 9
Fig. 9
3D surface plot of the release model.
Fig. 10
Fig. 10
Cumulative % released from optimized liposomal formulation.
Fig. 11
Fig. 11
TEM of optimized propolis liposomes.
Fig. 12
Fig. 12
In vitro 3CL-protease inhibition.
Fig. 13
Fig. 13
Inhibition of viral replication by Propolis extract, alcohol, propolis liposomes and control.
See this image and copyright information in PMC

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