Effect of liposomal celecoxib on proliferation of colon cancer cell and inhibition of DMBA-induced tumor in rat model

Abstract

Celecoxib, a selective cyclooxygenase-2 inhibitor, has shown potential anticancerous activity against majority of solid tumors especially on patients with colon cancer. However, associations of serious side effects limit the usage of celecoxib in colon cancer treatment. To address this issue and provide an alternative strategy to increase the efficacy of celecoxib, liposomal formulation of celecoxib was prepared and characterized. Anticancer activity of liposomal celecoxib on colon cancer cell HCT 15 was evaluated in vitro. Furthermore, tumor inhibition efficiency by liposomal celecoxib was studied on 7,12-dimethyl benz(a)anthracene (DMBA)-induced tumor in rat model. In order to elucidate the antioxidant activity of celecoxib-loaded liposomes, antioxidant superoxide dismutase (SOD) generation and lipid peroxide (LPx) formation in both liver and kidney tissues were examined. Characterization of the formed unilamellar liposomes revealed the formation of homogeneous suspension of neutral (empty) or anionic (celecoxib-loaded) liposomes with a well-defined spherical shape which have a mean size of 103.5 nm (empty liposome) and 169 nm (liposomal celecoxib). High-performance liquid chromatography (HPLC) analysis and hemolytic assay demonstrated 46% of celecoxib entrapment efficiency and significantly low hemolysis, respectively. Liposomal celecoxib exhibited dose-dependent cytotoxicity and apoptotic activity against HCT 15 cells which are comparable to free celecoxib. In vivo study demonstrated inhibition of tumor growth. Biochemical analysis of the liposomal celecoxib-treated group significantly inhibited the LPx formation (oxygen-free radicals) and increased the activity of SOD. Our results present the potential of inhibiting colon cancer in vitro and DMBA-induced tumor in rat model in vivo by liposomal celecoxib.

In Vitro Characterization of a Liposomal Formulation of Celecoxib Containing 1,2-Distearoyl-sn-Glycero-3-Phosphocholine, Cholesterol, and Polyethylene Glycol and its Functional Effects Against Colorectal Cancer Cell Lines

“…In the current study, the percentage of CLX incorporation to the cholesterol‐containing LUVs was greater than 70%. A recent study reported a 46% of entrapment efficiency for cholesterol‐free CLX‐loaded liposomes (DSPC only) prepared by sonication instead of extrusion . An immunoliposomal formulation containing CLX targeted to vascular cell adhesion molecule‐1 was prepared with 1,2‐dimyristoyl‐ sn ‐glycero‐3‐phosphocholine, cholesterol, and 1,2‐dipalmitoyl‐ sn ‐glycero‐3‐phosphoethanolamine‐ n ‐(glutaryl) in 65:25:10 or 70:25:5 mol % by sonication.…”

“…A recent study reported a 46% of entrapment efficiency for cholesterol-free CLX-loaded liposomes (DSPC only) prepared by sonication instead of extrusion. 29 An immunoliposomal formulation containing CLX targeted to vascular cell adhesion molecule-1 was prepared with 1,2-dimyristoyl-sn-glycero-3phosphocholine, cholesterol, and 1,2-dipalmitoyl-sn-glycero-3phosphoethanolamine-N-(glutaryl) in 65:25:10 or 70:25:5 mol % by sonication. This preparation was reported to result in 208 -308 :g/mL CLX that corresponds to 2.7%-3% loading.…”

Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

“…MTT-assay for MCF-7 and MBA-MB-231 cytotoxicity was used, as before 29 30 . Briefly, 100 μl of 2 × 10 3 cells were seeded into each well of a 96-well plate.…”

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

“…Small molecule inhibitors have advantages over larger molecules, such as monoclonal antibodies. These advantages include easy diffusion across the cell membrane, which facilitates large-scale experiments in which there might be difficulties in transfection or knockdown using RNAi (Gowda, Jones, Banerjee, & Robertson, 2013; Madani, Naderi, Dissanayake, Tan, & Seifalian, 2011; Parhi, Mohanty, & Sahoo, 2012; Perumal, Banerjee, Das, Sen, & Mandal, 2011). Small molecule inhibitors can be administered orally, whereas biologics generally require injection or another parenteral administration.…”