Capecitabine

Female BALB/c mice were obtained from the Animal Resource Centre (Canning Vale, WA, Australia) at 6–8 weeks of age and observed for at least 1 week prior to beginning experiments.Mice were injected with 5 ×10⁴ 4T1 cells per 10 ml PBS into the 2nd mammary fat pad on the right hand side to initiate tumour development. Daily treatment was started 6 days post-inoculation when tumours were palpable in the majority of mice. Throughout the course of the experiment, approximately 5% of animals did not form tumours. Mice were divided into seven groups of six and administered, via orogastric gavage, the following daily treatments for 21 days (calculations are based on a 20 g mouse): 0.5 mmol 5-FCOle, 0.25 mmol 5-FCOle, 0.1 mmol 5-FCOle, 0.5 mmol Capecitabine, 0.25 mmol Capecitabine, 0.1 mmol Capecitabine, or a 1.5 mg ml^-1 solution of F127 in water. The length and breadth of the tumors were measured on days 1, 4, 7, 14, and 21 of drug administration. Mice were euthanized on day 22 of drug administration. Blood was collected via cardiac puncture, followed by removal of the tumour, liver, spleen and kidney for histological analysis. Lungs were injected with indium ink prior to removal to allow for examination and quantification of lung metastases in each animal.

Because of many advanced methods for the detection of anticancer drugs, many anticancer agents now have been detected in aquatic systems; for example, 5-fluorouracil (5-FU), ifosfamide, and cyclophosphamide, and several new compounds, such as imatinib mesylate (IM), and temozolomide, and capecitabine (CAP). CAP is a new oral anticancer drug, playing its role by converting to the active compound 5-FU in vivo. 5-FU and its pro-drug CAP are pyrimidine analogues characterized as antimetabolites. This class of drugs inhibits DNA polymerase and induces cell cycle arrest and apoptosis. Because of a better clinical curative effect and higher security, CAP is popular with cancer patients and has been detected as a new compound in environmental samples, thus expanding the list of anticancer drugs measured in the environment. Based on therapeutical function and on the biological mode of action, certain groups of anticancer drugs are suspected to cause damage to key organisms in ecosystems. Thus, the environmental risk assessment for CAP in Europe has been considered and experienced.

Conventional drug delivery techniques are time consuming, painful and can cause side effects. As such, there is a need for alternative, high throughput, cost effective and user friendly laboratory drug screening methods for highly efficient drug testing. Current trends in point-of-care, automatized and precise drug assay platforms are superior to conventional techniques. Because they can achieve higher accuracy with lower drug dosages. Microfluidic based platforms have emerged as an efficient chip based assay for cell line tests. With their in-built advantages of low reagent consumption, precise control and high throughput scalability will provide robust analytical tools to investigate complex biological processes at the cellular level. Depending on cancer type and location of cancer, anticancer drugs will have specific targeting sites. For example, 5-fluorouracil and capecitabine drugs are anti- metabolites, irinotecan is a plant alkaloid and acts as a topo-isomerase inhibitor, folinic acid is a chemo-protectant, which causes folic acid deficiency in cancer cells, which leads to cell death, oxaliplatin is alkylating agent used for inhibiting cell cycles, bevacizumub is a genetically modified drug for regulating angiogenesis by inhibiting vascular endothelial factor and cetuximub is a protein based drug, which targets endothelial growth factor receptor proteins.

Capecitabine (Cap), chemically 50-deoxy-5-fluoro-N4-pentyloxycarbonyl-cytidine (Scheme 1) is the pro-drug for the anti-metabolite 5-fluorouracil (5-FU). It is a novel oral tumor- activated and tumor-elective fluoropyrimidine carbamate and an oral chemotherapeutic agent used in the treatment of breast, esophageal and larynx, gastrointestinal and genitourinary tract cancers. As a prodrug, Cap is converted into the active agent 5-fluorouracil (5-FU) through a three-step enzymatic process after oral drug administration. First, hydrolysis by carboxylesterases leads to the formation of 5’-deoxy-5-fluorocytidine (DFCR). Second, cytidine deaminase catalyzes the conversion of DFCR to 5’-deoxy-5-fluorouridine (DFUR). Finally, further catabolism by thymidine phosphorylase produces 5-FU.