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Use of polyglycerol (PG), instead of polyethylene glycol (PEG), prevents induction of the accelerated blood clearance phenomenon against long-circulating liposomes upon repeated administration
Faculty
Pharmacy
Year:
2013
Type of Publication:
Article
Pages:
235-242
Authors:
Shimizu, Taro, Ishida, Tatsuhiro, Kiwada, Hiroshi, Abu Lila, Amr S, Nawata, Kosuke
DOI:
10.1016/j.ijpharm.2013.07.059
Journal:
INTERNATIONAL JOURNAL OF PHARMACEUTICS ELSEVIER SCIENCE BV
Volume:
456
Research Area:
Pharmacology \& Pharmacy
ISSN
ISI:000324523400027
Keywords :
Accelerated blood clearance (ABC) phenomenon, Anti-PEG IgM, Polyethylene glycol (PEG), Polyglycerine (PG), Repeated administration
Abstract:
The accelerated blood clearance (ABC) phenomenon accounts for the rapid systemic clearance of PEGylated nanocarriers upon repeated administrations. IgM production against the polyethylene glycol (PEG) coating in PEGylated liposomes is now known to be responsible for such unexpected pharmacokinetical alterations. The ABC phenomenon poses a remarkable clinical challenge by reducing the therapeutic efficacy of encapsulated drugs and causing harmful effects due to the altered tissue distribution pattern of the drugs. In this study, we investigated the in vivo performance of liposomes modified with polyglycerol (PG) upon repeated injection, and the in vivo therapeutic efficacy of such liposomes when they encapsulated a cytotoxic agent, doxorubicin (DXR). Repeated injection of PEG-coated liposomes in rats induced the ABC phenomenon, while repeated injection of PG-coated liposomes did not. In addition, DXR-containing PG-coated liposomes showed antitumor activity that was superior to that of free DXR and similar to that of DXR-containing PEG-coated liposomes upon repeated administration. These results indicate that polyglycerol (PG) might represent a promising alternative to PEG via enhancing the in vivo performance of liposomes by not eliciting the ABC phenomenon upon repeated administration. (C) 2013 Elsevier B.V. All rights reserved.
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