Development and structural characterization of a novel nanoemulsion for oral drug delivery

The objective of this work has been to develop a template for the design and characterization of dried nanoemulsion (NE) for oral administration of hydrophobic compounds. A rational optimization of the nanosystem using an experimental design was performed to achieve stable NE of 100 nm with a neutral surface potential. NE were able to efficiently encapsulate the model drug tacrolimus, providing a sustained drug release in both simulated gastric fluid (SGF) and simulated intestinal fluid in fasted state (FaSSIF-V2). To improve long-term physical stability NE were dried using spray-drying and freeze-drying. Following reconstitution in water, they maintain their physicochemical properties without alteration. The highest process yield was obtained by freeze-drying using very low amount of cryoprotectant overcoming the major challenges related with the production of dry powders from oil based systems. Then, in order to improve the current structural analysis of nanocarriers an original characterization of the NE, with an in-depth focus on the NE shell nature was performed. Through X-ray diffraction and differential scanning calorimetry (DSC) measurements we demonstrated that the NE shell was amorphous when in colloidal suspension and crystalline upon drying. We also developed a novel polarity-sensitive fluorophore to assess the NE shell fluidity when in colloidal suspension. Globally, in the work here presented a relationship between the fluidity of the NE shell and the structure of used excipients was established. The gained evidences on the NE structure will contribute to a more rational design of nanosystems, opening the way to novel applications in oral drug delivery.