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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 SGF (simulated gastric fluid) and FaSSIF-V2 fluid (simulated intestinal fluid in fasted state). To improve their 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 freezedrying using very low amount of cryoprotectant, overcoming 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 structural characterization of the NE, with an in-depth focus on the NE shell nature was then 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.

This work combines natural polymers with nanoemulsions (NEs) to formulate nanocomposites as an innovative wound dressing. Spray-drying has been used to produce alginate-pectin in situ gelling powders as carriers for NEs loaded with curcumin (CCM), a model antimicrobial drug. The influence of NEs encapsulation in polymer-based microparticles was studied in terms of particle size distribution, morphology, and stability after spray-drying. NEs loading did not affect the size of microparticles which was around 3.5 µm, while the shape and surface morphology analyzed using scanning electron microscope (SEM) changed from irregular to spherical. Nanocomposites as dried powders were able to form a gel in less than 5 min when in contact with simulated wound fluid (SWF), while the value of moisture transmission of the in situ formed hydrogels allowed to promote good wound transpiration. Moreover, rheologic analyses showed that in situ formed gels loaded with NEs appeared more elastic than blank formulations. The in situ formed gel allowed the prolonged release of CCM-loaded NEs in the wound bed, reaching 100% in 24 h. Finally, powders cytocompatibility was confirmed by incubation with keratinocyte cells (HaCaT), proving that such nanocomposites can be considered a potential candidate for wound dressings. Graphical Abstract

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This work combines natural polymers with nanoemulsions (NEs) to formulate nanocomposites as innovative wound dressing. Spray drying has been used to produce alginate-pectin in situ gelling powders as carriers for NEs loaded with curcumin (CCM), a model antimicrobial drug. The influence of NEs encapsulation in polymer-based microparticles was studied in terms of particle size distribution, morphology, and stability after spray drying. NEs loading did not affect the size of microparticles which was around 3.5 µm, while the shape and surface morphology analyzed using scanning electron microscope (SEM), changed from irregular to spherical. Nanocomposites as dried powders were able to form a gel in less than 5 minutes when in contact with simulated wound fluid (SWF), while the value of moisture transmission of the in situ formed hydrogels allowed to promote good wound transpiration. Moreover, rheologic analyses showed that in situ formed gels loaded with NEs appeared more elastic than blank formulations. The in situ formed gel allowed the prolonged release of CCM-loaded NEs in the wound bed, reaching 100% in 24 hours. Finally, powders cytocompatibility was confirmed by incubation with keratinocyte cells (HaCaT), proving that such nanocomposites can be considered a potential candidate for wound dressings.