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Contact hypersensitivity: a simple model for the characterization of disease-site targeting by liposomes

Authors
  • Klimuk, Sandra K.
  • Semple, Sean C.
  • Scherrer, Peter
  • Hope, Michael J.
Type
Published Article
Journal
Biochimica et Biophysica Acta (BBA) - Biomembranes
Publisher
Elsevier
Publication Date
Jan 01, 1999
Accepted Date
Dec 21, 1998
Volume
1417
Issue
2
Pages
191–201
Identifiers
DOI: 10.1016/S0005-2736(98)00261-2
Source
Elsevier
Keywords
License
Unknown

Abstract

A murine model of delayed-type hypersensitivity (DTH) is characterized with respect to liposome accumulation at a site of inflammation. Mice were sensitized by painting the abdominal region with a solution of 2,4-dinitrofluorobenzene (DNFB) and inflammation was induced 5 days later by challenging the ear with a dilute solution of DNFB. The inflammatory response was readily monitored by measuring ear thickness (edema) and radiolabeled leukocyte infiltration. Maximum ear swelling and cellular infiltration occurred 24 h after the epicutaneous challenge with the ear returning to normal size after approximately 72 h. We demonstrate that large unilamellar vesicles (LUV) accumulate at the site of inflammation to a level more than 20-fold higher than that measured in the untreated ear. Vesicle delivery to the ear correlated with increased vascular leakage resulting from endothelium remodeling in response to DNFB challenge, and was not a consequence of increased local tissue blood volume. Extravasation occurred only during the first 24 h after ear challenge; after this time the permeability of the endothelium to vesicles returned to normal. We further showed that LUV with a diameter of 120 nm exhibit maximum levels of accumulation, that a polyethylene glycol surface coating does not increase delivery, and that the process can be inhibited by the application of topical corticosteroids at the time of induction. These data and the inflammation model are discussed with respect to developing lipid-based drug delivery vehicles designed to accumulate at inflammatory disease sites.

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