In acute oral toxicity LD50 value obtained was 4541.1067 mg/ kg. In repeated dose 28 day subacute oral toxicity study, hematological parameters viz., TEC, Hb, Hct and TLC showed significant decreased level in treated groups. Similarly biochemical parameters viz., aspartate aminotransferase, alanine aminotransferase, BUN, creatinine showed significant increased level in treated groups. There was a significant decrease in body weight gain in treated groups. Satellite high dose group animals showed partial recovery in terms of haematological, biochemical parameters and body weight gain after cessation of norfloxacin administration. Histopathology of both male and female rats revealed toxic effect of norfloxacin on liver, kidney, heart, spleen and intestines. Satellite high dose group showed recovery to normalcy in histopathological study.
Worldwide, a number of research groups are functioning towards effective treatment of colon cancer using chemotherapeutic agents. Nonsteroidal anti-inflammatory drugs are among the most potent agents discovered for the inhibition of cancer. In spite of the approval of celecoxib for adjuvant therapy in patients with familial adenomatous polyposis and precancerous disease of colon, associations of larger intensity of side effects limit its usage in cancer therapy. Combination therapy provides advantages of reduction in dose and possible reduction in toxicity and acquired drug resistance. As a consequence, targeted drug delivery and targeted molecular therapy of single or combination of anticancer agents are necessary for efficient treatment of colon cancer with reduced toxicity. In our study, combination of celecoxib and AEE788 shows growth inhibition and apoptosis in HCT 15 cells. Further, nanocarrier mediated celecoxib delivery showed high entrapment efficiency, sustained release patterns, desirable hemocompatibility and enhanced cytotoxicity and apoptosis in vitro and in vivo.