期刊
JOURNAL OF CONTROLLED RELEASE
卷 129, 期 3, 页码 179-186出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2008.04.021
关键词
fusion protein; tumor necrosis factor alpha; soluble tumor necrosis factor receptor; drug depot; elastin-like polypeptide
资金
- NIH [R01EB002263, R21AR052745, R01GM061232]
- Pratt-Gardner Predoctoral Research Fellowship
Numerous antagonists of tumor necrosis factor alpha (TNF alpha) have been developed to attenuate inflammation and accompanying pain in many disease processes. Soluble TNF receptor type II (sTNFRII) is one such antagonist that sequesters TNF alpha away from target receptors and attenuates its activity. Systemic delivery of soluble TNF receptors or other antagonists may have deleterious side effects associated with immune suppression, so that strategies for locally targeted drug delivery are of interest. Elastin-like polypeptides (ELPs) are biopolymers capable of in situ drug depot formation through thermally-driven supramolecular complexes at physiological temperatures. A recombinant fusion protein between ELP and sTNFRII was designed and evaluated for retention of bivalent functionality. Thermal sensitivity was observed by formation of supramolecular submicron-sized particles at 32 degrees C, with gradual resolubilization from the depot observed at physiological temperatures. In vitro refolding of the sTNFRII domain was required and the purified product exhibited an equilibrium dissociation constant for interacting with TNF alpha that was seven-fold higher than free sTNFRII Furthermore, anti-TNF activity was observed in inhibiting TNR alpha-mediated cytotoxicity in the murine L929 fibrosarcoma assay. Potential advantages of this ELP-sTNFRII fusion protein as an anti-TNFa drug depot include facility of injection, in situ depot formation, low endotoxin content, and functionality against TNF alpha. (C) 2008 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据