Routes of administration and dose optimization of soluble antigen arrays in mice with experimental autoimmune encephalomyelitis

Sharadvi Thati, Christopher Kuehl, Brittany Hartwell, Joshua Sestak, Teruna Siahaan, M. Laird Forrest, Cory Berkland

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Soluble antigen arrays (SAgAs) were developed for treating mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. SAgAs are composed of hyaluronan with grafted EAE antigen and LABL peptide (a ligand of ICAM-1). SAgA dose was tested by varying injection volume, SAgA concentration, and administration schedule. Routes of administration were explored to determine the efficacy of SAgAs when injected intramuscularly, subcutaneously, intraperitoneally, intravenously, or instilled into lungs. Injections proximal to the central nervous system (CNS) were compared with distal injection sites. Intravenous dosing was included to determine if SAgA efficiency results from systemic exposure. Pulmonary instillation (p.i.) was included as reports suggest T cells are licensed in the lungs before moving to the CNS. Decreasing the volume of injection or SAgA dose reduced treatment efficacy. Treating mice with a single injection on day 4, 7, and 10 also reduced efficacy compared with injecting on all three days. Surprisingly, changing the injection site did not lead to a significant difference in efficacy. Intravenous administration showed efficacy similar to other routes, suggesting SAgAs act systemically When SAgAs were delivered via p.i., however, EAE mice failed to develop any symptoms, suggesting a unique lung mechanism to ameliorate EAE in mice.

Original languageEnglish (US)
Pages (from-to)714-721
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume104
Issue number2
DOIs
StatePublished - Feb 2015
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the NIH (R56 AI091996), PhRMA Foundation Pre-Doctoral Fellowship, and NIH Vaccinogenesis Training Grant (NIH0066336). Christopher Kuehl acknowledges receiving financial support provided by Dynamic Aspects of Chemical Biology Training Grant (T32 GM08545). Brittany Hartwell would like to acknowledge the Madison and Lila Self Graduate Fellowship for financial support.

Publisher Copyright:
© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Keywords

  • Biomaterials
  • Experimental autoimmune encephalomyelitis
  • Facilitated diffusion/transport
  • HPLC
  • Hyaluronan
  • Immunology
  • Peptides
  • Polymeric drug delivery system
  • SJL mice

Fingerprint

Dive into the research topics of 'Routes of administration and dose optimization of soluble antigen arrays in mice with experimental autoimmune encephalomyelitis'. Together they form a unique fingerprint.

Cite this