Liposomes for inhalation have high biosafety and can achieve slow and controlled delivery, which are especially suitable for the treatment of lung diseases and have a promising clinical application prospect. However, liposomes for inhalation have the key bottleneck problem of the lack of strategies to control the targeting region, which restricts its clinical transformation. The root cause is the inability to control the bio-corona (BC) generation upon liposomes, which dominates the specific targeting regions. In order to overcome the above bottleneck, a high density hybrid liposome system based on distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) (DSPE-PEG) may be a potential choice. The PEG chain in DSPE-PEG has "stealth" effect that can hinder the adsorption of biological molecules. When the density of DSPE-PEG hybridization is high, the "stealth" effect is more significant, and the total adsorption amount of liposomal BC can be effectively reduced. By optimizing the PEG chain structures of DSPE-PEG, viz PEG chain length and terminal group modification, DSPE-PEG high density hybrid liposomes can be endowed with the function of targeting site regulation based on BC domination effect. It is believed that this proposed system can promote the profound reform of the research paradigm of inhalational liposomes, and accelerate the development of related products.
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