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44 IMMUNONIOSOMES TARGETED TO VASCULAR INFLAMMATION.
  1. E. Hood1,
  2. M. Gonzalez1,
  3. A. Plaas2,
  4. J. Strom1,
  5. M. VanAuker1
  1. 1Biomedical Engineering Program, Department of Chemical Engineering, University of South Florida, Tampa, FL
  2. 2Division of Rheumatology, College of Medicine, University of South Florida, Tampa, FL

Abstract

Vascular inflammation has been shown to initiate and propagate multiple cardiovascular pathologies; atherosclerosis is promoted and accelerated by inflammatory mechanisms. Site-specific therapies that target chronic pathological inflammation could greatly impact the completion of the AHA's stated impact goal "to reduce coronary heart disease, stroke and risk by 25 percent. " Interruption of the inflammatory process has been studied using the cell surface glycoprotein CD44 blocked by antibody IM7. CD44 is a principal receptor for hyaluronan, a major component of extracellular matrices, and is expressed in parenchymal cells and leukocytes. Dramatic suppression of inflammation was achieved through the highly selective binding of the antibody-antigen couple as shown by Krettek et al, 2004. We have synthesized nonionic surfactant vesicles, niosomes, by thin-film hydration methods using a mixture of biocompatible sorbitan ester surfactants and cholesterol. We conjugated them to IM7 antibodies through a novel polyoxyethylene sorbitan monostearate-cyanuric chloride linker incorporated in the vesicle membrane. The figure shows that the resulting "immunoniosomes " bind selectively and specifically to CD44 antigen targets on synoviocytes, our initial cell model, at IgG concentrations far lower than advocated by traditional immunoliposome literature. Bovine aortic endothelial cell models express CD44 and show enhanced binding of immunoniosomes when activated with proinflammatory cytokines such as interleukin-1-beta.

Figure.

Contrast and fluorescence overlay of IM7 conjugated immunoniosomes adhering to the surfaces of CD44-expressed synovial lining cells. The niosomes contain carboxyrhodamine 110 (CR), a fluorophore.

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