Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.

Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.

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

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.