PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats

Abstract

Polylysine dendrimers have potential as highly flexible, biodegradable nanoparticular carriers that may also promote lymphatic transport. The current study was undertaken to determine the impact of PEGylation on the absorption and lymphatic transport of polylysine dendrimers modified by surface derivatisation with PEG (200, 570 or 2000 Da) or 4-benzene sulphonate following SC or IV dosing. PEGylation led to the PEG 200 derived dendrimer being rapidly and completely absorbed into the blood after SC administration, however only 3% of the administered dose was recovered in pooled thoracic lymph over 30 h. Increasing the PEG chain length led to a systematic decrease in absorption into the blood and an enhancement of the proportion recovered in the lymphatics (up to 29% over 30 h). For the PEG 570 and PEG 2000 derived dendrimers, indirect access to the lymph via equilibration across the capillary beds also appeared to play a role in lymphatic targeting after both IV and SC dosing. In contrast, the anionic benzene sulphonate-capped dendrimer was not well absorbed from the SC injection site (26% bioavailability) into either the blood or the lymph. The data suggest that PEGylated poly-L-lysine dendrimers are well absorbed from SC injection sites and that the extent of lymphatic transport may be enhanced by increasing the size of the PEGylated dendrimer complex.