Factors governing the in vivo tissue uptake of transferrin-coupled polyethylene glycol liposomes in vivo

Liposomes, coated with transferrin (Tf)-coupled polyethylene glycol are considered to be potent carriers for drug delivery to various organs via receptor-mediated endocytosis. Since Tf receptors were ubiquitously expressed in various organs, additional perturbation of the liposomes such as regulation of the size may be required to exhibit the tissue selectivity. In the present study, the effect of size on the uptake of transferrin-coupled polyethylene glycol liposomes (Tf-PEG-L) to various organs was investigated. In liver and brain, Tf-dependent uptake was found to be dependent on the size of the liposomes used. In small liposomes with a diameter of 60-80 nm, Tf-PEG-L was taken up to these organs more efficiently than PEG-L. This Tf-dependent uptake for small liposomes decreased by the high dose administration, suggested that Tf-PEG-L is taken up via Tf receptor-mediated endocytosis even under the physiological condition, in which plasma concentration of endogenous Tf remains high. On the other hand, Tf receptor-mediated uptake was also observed in the heart, but size-dependency was not observed in this case. Collectively, these results indicate that size dependency in the uptake of Tf-PEG-L is tissue-dependent and therefore, controlling the size of Tf-PEG-L may be useful for the success of tissue targeting.