The overall goal of the proposed research is to develop novel drug delivery systems that are based on the self-association properties of fluorinated amphiphilic polymers. Aqueous solutions of the proposed amphiphilic molecules yield nanostructures such as micelles and nanoemulsions that are characterized by a fluorous inner core and that can be used for the encapsulation and intravenous delivery of highly fluorinated Pharmaceuticals, such as volatile fluorinated anesthetics. These are the most common and powerful anesthetics used in the United States. They are usually administered by inhalation. Advantages of intravenous delivery of volatile anesthetics include the ability to more rapidly induce anesthesia than is possible using inhalation methods, and a more rapid awakening than even propofol produces. Furthermore, patient hyperventilation is eliminated and blood-born infections (related to IntraLipid formulations) are reduced. We have preliminary results that show that our semifluorinated polymers can form micelles and stable nanoemulsions able to either encapsulate or emulsify all known fluorinated anesthetics. Our formulations allow the water solubilization of record volumes of volatile fluorinated anesthetics: up to 30 % in volume. Anesthetic release from the fluoroemulsions is studied through a combined in vitro and in vivo approach. The effect of the released anesthetic on the GABAA receptor is used to determine the concentration of free anesthetic in our formulations as well as its time-controlled release. Animal studies have been used to prove the efficacy of the proposed approach and are used to find: 1) The most effective formulation for the intravenous delivery of volatile anesthetics. 2) Prove that the proposed amphiphiles and formulations are devoid of any toxicity. Relevance to public health. The proposed research will provide nanocarriers with the ability of complexing and delivering volatile anesthetics by intravenous injection. This will allow a significant clinical improvement of general anesthesia. Rapid incorporation into the routine practice of anesthesiology is foreseen for the research described in this proposal. ? ? ?
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