Abstract
This thesis focused on the design of amphiphilic systems resulting from the self-association of new hybrid nonionic fluorinated/hydrogenated surfactants with a PEGylated or a glucose polar head. In water, these surfactants were found to form different types of stable aggregates, micelles for the PEG series and vesicles for the Glucose series, and thus could be used for the encapsulation and vectorization of hydrophobic drugs. We developed a versatile multi-step synthesis of an hybrid building block with a serine core which was then grafted to a polar head by a copper(I)-mediated azide-alkyne cycloaddition (CuAAC) reaction to lead to the F–H hybrid surfactants. A thorough study of their self-assembly properties i.e. cmc, aggregation number, size and stability of the aggregates was carried out. We demonstrated that subtle changes in the chemical structure can change the nature and the size of the aggregates with the F6 PEG series forming rather small and compact micelles, those of the F8 PEG being larger and likely well-defined while the two Glucose compounds form vesicles. Finally, preliminary encapsulation trials of Paclitaxel (PTX), an hydrophobic chemotherapeutic agent, were carried out using a hybrid PEGylated surfactant from the F8 series. Despite low drug-loading and rapid burst-release, cell viability tests on pulmonary cancer lines showed that PEGylated F8 alone is biocompatible and that PEGylated F8/PTX formulation does not inhibit the activity of PTX in the micellar formulation.