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

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


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.

MeSH terms

  • Antiviral Agents / administration & dosage
  • COVID-19 / metabolism
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • COVID-19 Nucleic Acid Testing
  • Coronavirus 3C Proteases / metabolism
  • Flavonoids / pharmacokinetics
  • Humans
  • Liposomes
  • Molecular Docking Simulation / methods
  • Outcome Assessment, Health Care
  • Propolis* / administration & dosage
  • Propolis* / pharmacokinetics
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / isolation & purification
  • SARS-CoV-2* / physiology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Flavonoids
  • Liposomes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Propolis
  • Coronavirus 3C Proteases