What are the disadvantages of PEGylated liposomes?

PEGylated liposomes are liposomes that are modified with polyethylene glycol (PEG). These modified liposomes offer several advantages, but they also have a few drawbacks including:  

• The PEG coating can interfere with the uptake of liposomes by target cells, reducing their effectiveness.
• PEG can hinder the escape of pH-sensitive liposomes (PSL) that are carried by the genes and protein drugs, leading to the degradation and failure of these drugs in the lysosome.  
• Repeated administration of PEGylated liposomes can trigger accelerated blood clearance, a phenomenon where they are cleared from the blood more quickly, reducing their effectiveness over time. Known as the ‘PEG dilemma’, this phenomenon poses a challenge in the development of PEGylated liposome-based therapies.