Date

2011-12-31

Author

Banerjee, Sreeparna

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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) enzyme in prostaglandin production pathway The anticarcinogenic effects of Celecoxib are not solely due to the inhibition of COX-2. COX-2 independent effects observed in vitro can be summarized as inhibition of cell cycle progression, induction of apoptosis, and inhibition of angiogenesis and metastasis (Grosch et al. 2006). Additionally, our studies with model membranes have indicated that celecoxib, a highly hydrophobic drug, significantly affects membrane properties such as fluidity and order (Sade, Banerjee and Severcan 2009). Although results of two clinical trials (i.e. APC: Adenoma Prevention with Celecoxib and PreSAP: Prevention of Spontaneous Adenomatomous Polyps) have controversial outcomes in terms of increased cardiovascular risks due to celecoxib use, the concern about these side effects persist. Therefore there is growing interest in developing drug delivery systems for celecoxib, for instance PLGA microparticles, chitosan microspheres, beta cylodextrin-drug complex in multilamellar liposomes (Jain et al. 2007, Thakkar et al. 2004) have been described for the delivery of celecoxib by different routes. Liposomes are artificially prepared vesicles made of lipid bilayer. While our current studies for the development of the liposome-based drug delivery system are still going on, some interesting discoveries were made during the optimizations of the procedure. They are related to the interaction of Celecoxib with Cholesterol in the lipid vesicles. The preliminary studies have shown that when relatively higher amount of cholesterol is present in liposome membranes, the properties of the vesicles are changed significantly if Celecoxib is present in the same vesicles. Vesicles are showing increased aggregation properties, which complicates the handling of the liposomes during some procedures, such as extrusion, and also increases the diameter of vesicles from the desired 100 nm to 1 µm. Additional studies done at our laboratory with some drugs commonly available in the market (Ibuprofen and Meloxicam) have shown that if those drugs are used instead of Celecoxib, or if no drug is used, there is no change in the properties of the liposomes, and the increased aggregation effect is not observed.

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https://hdl.handle.net/11511/59845

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Graduate School of Natural and Applied Sciences, Project and Design