Colorectal carcinoma (CRC) is one of the most common cancers and is the leading
cause of cancer deaths in much of the developed world. Owing to the high
incidence of drug resistance and potential toxic effects of chemotherapy drugs,
much research is currently underway to design better strategies for smart drug
delivery systems. Cyclooxygenase-2 (COX-2) pathway is associated with poor
prognosis in colon carcinomas. The selective COX-2 inhibitor drug Celecoxib
(CLX) has been shown to posses COX-2 independent anti-carcinogenic effects in
addition to inhibition of prostaglandins synthesis. The aim of the presented thesis
was to develop a liposomal delivery system for CLX and to evaluate functional
effects in CRC cell lines. Starting with multilamellar vesicles capable of CLX
encapsulation and retention, nano sized liposomes were prepared and characterized
in vitro. The optimum composition was determined as 10:1 DSPC: Cholesterol molar ratio and Polyethylene glycol (PEG) grafting at 2% of phospholipids. The
extent of cellular association of PEGylated liposome formulation was analyzed
quantitatively and cellular localization was analyzed qualitatively. We detected that
CLX loaded PEGylated liposomes inhibited proliferation and cellular motility of
cancer cells in a 2D model system. Our results showed that, Epidermal Growth
Factor Receptor (EGFR) targeted CLX loaded immunoliposomes were extremely
cytotoxic in cancer cells with high EGFR expression but not in cells devoid of
EGFR expression. This delivery system may pioneer studies that may potentially
circumvent the harmful systemic side effects of cancer preventive and
chemotherapy drugs as well as allow the use of targeted combinatorial therapies.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12614271/index.pdf |
| Date | 01 April 2012 |
| Creators | Erdog, Asli |
| Contributors | Banerjee, Sreeparna |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | Ph.D. Thesis |
| Format | text/pdf |
| Rights | Access forbidden for 1 year |
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