Liposomes, clearance PEGylated

Several liposome-based drugs have been approved for clinical application [64]. One of the clinically approved liposomes is Doxil, a PEGylated liposome containing doxorubicin (DOX), which is used for the treatment of a number of diseases [65]. As shown in this case, in the field of liposome drug development, PEG is widely used to protect the liposome from recognition by opsonins, thereby reducing liposome clearance. 

Ishida T, Kiwada H (2008) Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int J Pharm 354 56-62... 

Xu H, Wang KQ, Deng YH, da Chen W (2010) Effects of cleavable PEG-cholesterol derivatives on the accelerated blood clearance of PEGylated liposomes. Biomaterials 31 4757-4763... 

Ishida, T., Ichihara, M., Wang, X., and Kiwada, H. (2006), Spleen plays an important role in the induction of accelerated blood clearance of PEGylated liposomes, /. Controlled Release, 115, 243-250. 

Self assembly using amphiphilic components to trap drug in solution within a hydrophobic or hydrophilic core has been explored for decades for the delivery of drugs. The most notable example is that of the liposome, which, however, suffered from low entrapment efficiency, leakage, and rapid clearance by the reticuloendothelial system of the liver. This rapid clearance was reduced by the use of PEGylated phospholipids to form of the so-called sterically stabilized or stealth liposomes. ... 

Ishida T et al (2005) Accelerated blood clearance of PEGylated liposomes following preceding liposome injection Effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes. J Control Release 105 305-317... 

In 10 patients the AUC of intravenous pegylated liposomal doxorubicin (Caelyx) 30 to 35 mg/m was increased by a mean of 80% when it was given with intravenous paclitaxel 70 or 175 mg/m. Peak plasma levels of doxorubicin were also increased and clearance was reduced by 71%. In 9 other patients given Caelyx with docetaxel 30 or 60 mg/m, the AUC of doxorubicin was increased by 12% and clearance reduced by only 16%. ... 

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