| In our daily life, there are thousands of people all over the world who encounter accident or disease and hence need to be medically treated. Since blood keeps body's cells alive by bringing them oxygen, blood transfusion is indispensable during the process of surgery. Therefore, the development of blood substitutes, which can carry the oxygen for therapeutic purpose, is of crucial importance. Due to its high gas-dissolving capacity, perfluorocarbon (PFC) has been considered and used as a blood substitute. But PFC liquids are immiscible with blood and other body fluids; they must be emulsified before intravascular administration to human bloodstream. However, PFC emulsions are rapidly phagocytosed by reticuloendothelial system (RES) cells and thereby lose their persistence in the circulatory system. Moreover, PFC emulsions once ingested could induce RES cells to release of pre-inflammatory cytokines that trigger a series of side effects (e.g. flu-like syndrome). In order to antagonize phagocytosis and concomitantly mitigate the side effects, innovative PFC emulsions endowed with phagocytosis-resistant features were developed in this thesis work. In view of polyethylene glycol (PEG) on prolonging circulation of stealth liposome for drug delivery, a plethora of polymeric fluorosurfactants composed of various structures were designed and synthesized. PFC emulsion microparticles prepared by these synthesized fluorosurfactants were incubated individually with J774A.1 macrophages. The experimental results showed that the extent of phagocytosis appears to be inversely proportional to the molecular weight of PEG moiety of synthetic fluorosurfactant. Moreover, the fluorosurfactant, using hydrophilic biopolymers (i.e., alginate and chitosan) as the backbone to connect perfluoroalkyl groups via PEG spacers, provided the PFC emulsions with anti-phagocytic function. Lastly, biomimetic PFC emulsions prepared by CD47 conjugated fluorosurfactants were proved to be a feasible and challenging approach to achieve long-circulating delivery of emulsified PFC microdroplets. In summery, it is surmised that a combination of molecular weight, structure/topology, biochemical, and physicochemical properties of fluorosurfactants need to be employed in the design and synthesis for attaining anti-phagocytic PFC-based colloidal oxygen carriers. |
