Many biological therapeutics are rarely used for drug delivery due in part to their poor solubility and permeability across biological barriers (i.e. tight cell junctions). Given the improved understanding in this area, there is currently a significant push to design nanocarriers. In particular, much attention has been focused on nanoemulsions, whose structure protects drugs against physico-chemical and enzymatic degradation. One class of nanoemulsions called perfluorocarbon (PFC) nanoemulsions are of particular interest because of their drug carrying and tumor-targeting capabilities. The objective of this study is to develop a novel class of nanoemulsion-based contrast agents for both cancer imaging and therapy by, i) optimizing the physical characteristics of PFC nanoemulsions for long term stability, ii) characterizing the physical properties of these agents and iii) testing whether these PFC nanoemulsions can be vaporized for ultrasound imaging.
Various low and high energy methods such as phase inversion temperature, phase inversion composition and sonication were used for making emulsions. These techniques are of particular interest because of their ability to provide high energy and ultrafine emulsions as well as their low operational costs. For characterizing size and morphology of emulsions, dynamic light scattering and various microscopic (i.e. scanning and transmission electron) techniques were used.
Results indicate that three major factors affecting nanoemulsion stability are, i) total sonication time, ii) concentration of the emulsifier Zonyl fluorosurfactant (FSP) and iii) perfluorohexane (PFH) to FSP concentration ratio. At a given emulsion composition, increasing the sonication time led to a decrease in emulsion size. On the other hand increasing the FSP concentration but lowering the PFH to FSP ratio led to smaller emulsions. These findings indicate that challenges in stability caused by physical mechanisms (i.e. flocculation, coalescence, Ostwald ripening) can be overcome by the choice of formulation and composition of the dispersive and continuous phase.