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Functional Application Of İmmununoliposomes Encapsulating Celecoxib On Colon Cancer Cell Lines.

Long term regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been correlated with reduced risk of variety of cancers. Celecoxib is a new generation NSAID that can selectively inhibit activity of cyclooxygenase-2 (COX-2) Celecoxib serves as a chemopreventive agent in colorectal cancer. Therefore there is growing interest in developing drug delivery systems for celecoxib, Targeting will be carried out by conjugation of a chimeric monoclonal antibody (Cetuximab) against the Epidermal Growth Factor Receptor (EGFR). EGFR, which binds to epidermal growth factor, is essential in the normal maintenance of cellular growth and function. However, the receptor is known to be dysregulated in 25-77% of colorectal cancers and 85% of metastatic colorectal cancers. In this project we propose to prepare PEGylated liposomes encapsulating celecoxib, which will be converted immunoliposomes by conjugating to an anti-EGFR antibody. The combined inhibition of COX-2 by celecoxib and EGFR by cetuximab has been previously shown to synergistically reduce the metastatic potential of breast cancer in in vivo models (Gupta et al., 2007). Preliminary studies carried out in our laboratory indicate successful liposomal encapsulation and release of celecoxib (Deniz, Sade, Severcan, Keskin, Tezcaner & Banerjee, 2009). We therefore propose that the immunoliposomal preparation for the targeted delivery of celecoxib may hold promise for future therapeutic opportunities in colon cancer.