PEGylated liposomes via ATRP for brain drug delivery

PEGylated liposomes play a critical role in drug delivery systems because they can evade immune recognition. However, conventional methods for synthesizing PEGylated liposomes often involve the direct incorporation of PEG-functionalized lipids, resulting in insufficient and inconsistent PEG distribution on the liposome surface, which compromises their stability and performance. In this study, we present a proof-of-concept synthesis approach that utilizes lipid-based initiators to form liposomes, followed by controllable grafting of PEG chains through atom transfer radical polymerization (ATRP). This method ensures controlled and uniform PEG coverage, resulting in improved functionality. Compared to conventional liposomes, the polymer-grafted liposomes synthesized via ATRP demonstrated superior cellular uptake <i>in vitro</i>, enhanced penetration of the blood-brain barrier (BBB), and improved stability <i>in vivo</i>, particularly for protein-encapsulated formulations such as green fluorescent protein (GFP). Live/dead assays confirmed the biocompatibility of the ATRP-synthesized PEGylated liposomes. Therefore, our strategy significantly enhances the efficiency of PEGylated liposomes for targeted brain drug delivery, providing a promising platform for the treatment of neurological disorders.