التفاصيل البيبلوغرافية
| العنوان: |
Targeting interleukin-4 to the arthritic joint. |
| المؤلفون: |
Spieler, Valerie1,2 (AUTHOR), Ludwig, Marie-Gabrielle3 (AUTHOR), Dawson, Janet3 (AUTHOR), Tigani, Bruno3 (AUTHOR), Littlewood-Evans, Amanda3 (AUTHOR), Safina, Caterina3 (AUTHOR), Ebersbach, Hilmar3 (AUTHOR), Seuwen, Klaus3 (AUTHOR), Raschig, Martina1 (AUTHOR), ter Mors, Björn1 (AUTHOR), Müller, Thomas D.4 (AUTHOR), Meinel, Lorenz1,5 (AUTHOR), Lühmann, Tessa1 (AUTHOR) tessa.luehmann@uni-wuerzburg.de |
| المصدر: |
Journal of Controlled Release. Oct2020, Vol. 326, p172-180. 9p. |
| مصطلحات موضوعية: |
*INTERLEUKIN-4, *GENETIC code, *MOIETIES (Chemistry), *MACROPHAGES, *RHEUMATOID arthritis, *AMINO acids |
| مستخلص: |
Anti-inflammatory cytokines are a promising class of therapeutics for treatment of rheumatoid arthritis (RA), but their use is currently limited by a rapid clearance and systemic toxicity. Interleukin-4 is a small cytokine with potential for RA therapy. To increase its pharmacokinetic features, we engineered a murine IL4 conjugate by incorporating an unnatural amino acid through genetic code expansion to which PEG-folate, as a targeting moiety and PEG alone as control, were site-specifically bound. Both IL4 conjugates retained bioactivity and induced primary murine macrophage polarization into an alternatively activated (M2) related phenotype. The PEGylated conjugates had a terminal half-life of about four hours in healthy mice compared to unPEGylated IL4 (0.76 h). We showed that both conjugates successfully accumulated into arthritic joints in an antigen-induced arthritis (AIA) mouse model, as assessed by non-invasive fluorescence imaging. The modular nature of the IL4 conjugate chemistry presented herein facilitates easy adaption of PEG chain length and targeting moieties for further improvement of half-life and targeting function for future efficacy studies. Unlabelled Image [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
