Yes / Ibuprofen (IBF) is an outstanding non-steroidal drug for analgesic and anti-inflammatory therapies but it exhibits poor solubility in water [1, 2]. Increased dosage administration has been linked to gastrointestinal and cardiovascular complications [3]. Many techniques have been employed to improve the solubility of NSAIDs [4]. In this study, the anti-solvent precipitation method was used to make Ibuprofen nanoparticles (IBF NPs). Optimised preparation parameters such as solvent (ethanol), raw drug concentration (400 mg), solvent/anti-solvent ratio (1:50) and surfactant concentration (0.25 mg/ml) have been studied to yield nanoparticles with a mean size of 58.8 nm, which is confirmed by dynamic light scattering and transmission electron microscopy. These IBF NPs posess increased aqueous solubility compared to the micro counterpart and maintain with chemical integrity indicated by high performance liquid chromatography and Fourier transform infrared spectroscopy. In addition, in vitro cytotoxicity of IBF NPs has been studied on A549 and HaCat cell lines using MTT and LDH assays. Both cells were obtained from ATCC. The A549 cells were grown in a modification of Ham’s F-12, containing L-glutamine, called F-12K. The HaCaT cells were grown in DMEM containing sodium pyruvate (110 mg/l). Normal cell culture and sub-culture were applied and the cells were used after around 45 passages [5]. The cell culture media containing 105cells/ml were placed in a 96-well plate with addition of IBF NPs and Micro form at concentrations in the range of between 6 and 500 ug/ml by diluting them with DMEM and F-12K for use with the HaCaT and A549 cells respectively. After 24, 48 and 72h exposure, the MTT and LDH cytotoxicity assay were performed in triplicates and on three separate experiment cultures and the absorbance was recorded at 570 nm and 492nm respectively with Elisa micro plate reader. The cell viability (%) related to control (cells in culture medium without NPs) was calculated. A very good cytotoxicity profile was observed, indicating an in vitro cytocompatibility of the IBF NPs in these cell culture systems and no significant changes in cytotoxicity compared with Micro IBF. We conclude that our IBF NPs have increased solubility, same chemical integrity and unchanged cytotoxicity compared to IBF Micro drug. Further work will concentrate on optimising more rigorous parameter to produce excellent quality NPs. More detailed characterisation of IBF NPs is to be tested, such as using PXRD and SEM to further corroborate particle shape and size. The range of no toxic in vitro concentrations is also to be further confirmed. Eventually scaled up preparation of IBF NPs will be developed without relinquishing NPs quality. This would improve the potential for in vitro/ in vivo applications and clinical use of IBF NPs and NSAIDs in general.

This project focuses on two important topics which may pose hazards to human health. Firstly, drinking water disinfection by-products (DBPs), which are generated by the chemical disinfection of water have been investigated. What has not been shown is the effect of DBPs in human germ cells as well as somatic cells and whether oxidative stress is involved in the mechanism of genotoxic action. Three different DBPs (halo acetic acids: HAAs), together with the antioxidants – catalase and butylated hydroxyanisole (BHA), were investigated in peripheral blood cells and sperm from healthy individuals using the Comet assay and lymphocytes only using the micronucleus assay. Secondly, nanoparticles of the non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and ibuprofen, have been investigated in patients with respiratory diseases, in the micronucleus assay and the Comet repair assay. NSAIDs inhibit cyclooxygenase enzyme activity, which plays part in tumour progression. In the Comet assay, BHA and catalase were able to reduce DNA damage in both cell types compared to HAAs alone. Similarly, in the micronucleus assay, micronuclei were reduced with the antioxidants, suggesting oxygen radical involvement in both assays. With the NSAIDs, reductions were seen for DNA damage in the micronucleus assay with aspirin and ibuprofen nanoparticles compared to their bulk forms. Using the Comet repair assay, aspirin and ibuprofen nanoparticles aided repair of DNA to a greater extent than their bulk counterparts, which in turn showed better repair compared to samples repaired without NSAIDs. These observations show the importance of DBPs and NSAIDs in genotoxic public health issues.

This project focuses on two important topics which may pose hazards to human health. Firstly, drinking water disinfection by-products (DBPs), which are generated by the chemical disinfection of water have been investigated. What has not been shown is the effect of DBPs in human germ cells as well as somatic cells and whether oxidative stress is involved in the mechanism of genotoxic action. Three different DBPs (halo acetic acids: HAAs), together with the antioxidants – catalase and butylated hydroxyanisole (BHA), were investigated in peripheral blood cells and sperm from healthy individuals using the Comet assay and lymphocytes only using the micronucleus assay. Secondly, nanoparticles of the non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and ibuprofen, have been investigated in patients with respiratory diseases, in the micronucleus assay and the Comet repair assay. NSAIDs inhibit cyclooxygenase enzyme activity, which plays part in tumour progression. In the Comet assay, BHA and catalase were able to reduce DNA damage in both cell types compared to HAAs alone. Similarly, in the micronucleus assay, micronuclei were reduced with the antioxidants, suggesting oxygen radical involvement in both assays. With the NSAIDs, reductions were seen for DNA damage in the micronucleus assay with aspirin and ibuprofen nanoparticles compared to their bulk forms. Using the Comet repair assay, aspirin and ibuprofen nanoparticles aided repair of DNA to a greater extent than their bulk counterparts, which in turn showed better repair compared to samples repaired without NSAIDs. These observations show the importance of DBPs and NSAIDs in genotoxic public health issues. / United Kingdom India Education and Research Initiative (UKIERI).