TY - JOUR
T1 - PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats
AU - Kaminskas, Lisa Michelle
AU - Kota, Jagannath
AU - McLeod, Victoria Mary
AU - Kelly, Brian Devlin
AU - Karellas, Peter
AU - Porter, Christopher John
PY - 2009
Y1 - 2009
N2 - 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 derivtisation with PEG 9200,570 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 does 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 the (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.
AB - 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 derivtisation with PEG 9200,570 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 does 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 the (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.
UR - http://wwww.elsevier.com/locate/jconrel doi:10.1016/jconrel.2009.08.005
U2 - 10.1016/jconrel.2009.08.005
DO - 10.1016/jconrel.2009.08.005
M3 - Article
VL - 140
SP - 108
EP - 116
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2
ER -