Synthesis of dibranched semifluorinated polymers for fluorous nanoemulsion-​based drug delivery

The introduction of fluorine atoms in an org. mol. considerably changes the properties of that compd. Fluorocarbons are more hydrophobic than hydrocarbons, resulting in their ability to form a fluorous phase, which is phase-​sepd. from both hydrophilic and lipophilic phases. The introduction of fluorocarbons in org. mols. thus results in amphiphilic character that can lead to self-​assembly into stable, well-​organized semifluorinated colloids. These nanoaggregates can be used in a variety of applications, nanoemulsions being one of the most promising. Nanoemulsions are composed of a hydrophobic-​oil nanodroplet core in which the hydrophobic drug is loaded. An amphiphilic polymer is then used to stabilize the emulsion in aq. soln. Fluorous nanoemulsions, stabilized by semifluorinated block copolymers, are particularly promising for controlled drug delivery. In order to investigate the drug release profile of fluorous nanoemulsions, two triphilic and dibranched semifluorinated polymers were synthesized. In both polymers, the hydrophilic unit is composed of poly(ethylene glycol) (PEG) that ensures water soly. and biocompatibility. The lipophilic block is a linear alkyl chain composed of eighteen carbon atoms. In one of the two synthesized polymers, the fluorous block comprises eight CF2-​residues and is placed between the hydrophilic and lipophilic blocks in both branches. The placement of the fluorous shell in an intermediate position between the PEG and the hydrophobic moiety shields the internal drug-​contg. oil droplet and allows controlled drug delivery. The second synthesized polymer is characterized by one shorter branch, composed of only the fluorous block. This design, when compared to that of the first polymer, allows the assessment of the relative importance of both the hydrophobic and fluorous blocks in the delivery properties of the corresponding nanoemulsions. Thus, we have investigated how varying the size and structure of semifluorinated polymers affects the formation and stability of nanoemulsions as well as the rate of drug release.