Contrast agent based on nano-emulsion for targeted biomedical imaging

X-ray imaging agents are essential in combination with X-ray computed tomography to improve contrast enhancement aiming at providing complete visualization of blood vessels and giving structural and functional information on lesions allowing the detection of a tumor. As well as it is fundamental tool to discriminate between healthy cells and pathogens. We successfully limit the problems presented in commercial Xray contrast agents like poor contrasting in Fenestra® VC associated with short blood circulation time and to avoid rapid renal elimination from the body as found in Xenetix (Iobitriol). We developed nontoxic and blood pool iodine-containing nano-emulsion contrast agents serving in preclinical X-ray μ-CT imaging such as, α- Tocopherol (vitamin E), Cholecalciferol (vitamin D3), Castor oil, Capmul MCMC8 oil and oleic acid. Those formulated nanoemulsions were prepared by low energy spontaneous emulsification technic with slight modification for each platform. They showed new specific features rendering them promising agents in in vivo experiments as improving the balance between the efficacy and the toxicity of targeted therapeutic interventions. We investigate the effect of size and the chemical composition of the nanoparticles on their biodistribution, pharmacokinetics and toxicity. They demonstrated that the chemical structures of the droplet’s cores have significant role in targeting for example vitamin E was mainly accumulated in liver and castor oil formulation was passively accumulated in spleen explaining the proof-of-concept of EPR effect. On the other hand, two different platform sizes of Cholecalciferol molecule revealing that no real impact on the pharmacokinetics and biodistribution but presented remarkable effect on the toxicity. Of particular interest is studying the effect of the surface charge of nanoparticles on their biodistribution, this is why oleic acid nano-emulsion was selected to proceed this study by presence of amphiphilepolymer poly(maleic anhydride-alt-1-octadecene) (PMAO). The in vitro results and in vivo evaluations were completely coherent approving that the neutral charged NPs are less toxic compared to the negatively charged ones that were highly uptaked in the cells causing stress to the cells and thereby affecting the toxicity. As a result they are different in biodistribution and pharmacokinetics. In this context, for the first time, we were able to functionalize the nano-emulsion droplets with ligand molecules by covalent bonds. Likewise we designed nano-droplets and coated by silica shell ended by amino groups and then followed by formation of amide bonds with grafting to dye ligand model (coumarin blue dye). The quantification of amino groups was performed by using spectroscopic and microscopic techniques, with a grafting efficiency as high as 41%. This process improves the targeting properties of such chemotherapeutic agents to the location of interest following active targeting mechanism (ligand receptorstrategy). One of our achieved objectives was to engineer multifunctional polymer-based NPs encapsulating hydrophobic drug model as DDs and iron oxide NPs as a theranostic model. To conclude, novel contrast agents and delivering systems were synthesized with outstanding physicochemical characteristics and suitable for in vivo medium with high efficacy and low toxicity.