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lymph node exposure to the protein VEGF-C

PostPosted: Fri Oct 28, 2011 11:04 am
by patoco
Influence of route of administration and liposomal encapsulation on blood and lymph node exposure to the protein VEGF-C156S.

Bhansali SG, Balu-Iyer SV, Morris ME.


Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Amherst, New York 14260-1200.


VEGF-C156S is a recombinant form of human vascular endothelial growth factor C (VEGF-C), which targets the receptor VEGFR-3 present in the lymphatics. VEGF-C156S has lymphangiogenic properties and may represent a potential therapeutic approach in treating the lymphatic disease lymphedema. In the present study, we tested the hypotheses that (1) subcutaneous (s.c.) injection will provide higher lymphatic exposure than intravenous (i.v.) administration of VEGF-C156S and (2) s.c. injection of liposomal (s.c. Lipo) VEGF-C156S will provide greater lymphatic exposure than nonliposomal proteins. The protein VEGF-C156S was radiolabeled with Iodine-125 by a modified chloramine-T method and encapsulated into liposomes. The protein was injected at a dose of 125 μg/kg to mice i.v. or s.c.; the liposomal preparation was administered s.c. (s.c. Lipo). Blood and lymph nodes were collected over 24 h. The mean residence time in lymph nodes after s.c. or s.c. (Lipo) administration was approximately double that following i.v. administration. The area under the concentration-time curve (AUC) ratio of lymph node-blood after s.c. administration of VEGF-C156S was more than double of the AUC ratio after i.v. administration. The results suggest that lymph node exposure of VEGF-C156S was significantly higher after s.c. administration of liposomal or nonliposomal protein as compared with i.v. administration. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.

Copyright © 2011 Wiley-Liss, Inc.