Compartmentalized algal-based nanocarriers as vectors for antioxidants: structural and functional characterization

The delivery of poorly water-soluble natural drugs is a longtime challenge that has led to the development of several solubilizing and encapsulating carrier systems, to administrate hydrophobic molecules for biomedical, pharmaceutical, food and cosmetics applications. Among the most popular soft matter nanocarriers, lipid-based vectors are particularly favored thanks to the advantageous properties of lipids used as versatile and biocompatible building blocks. Indeed, lipids are the class of bio-macromolecules with the richest polymorphism and spontaneous self-assembly character, that result in a broad variety of hierarchical structures. Several aggregates with various interfacial curvatures and symmetries can be obtained, mainly depending on the lipid class and packing parameter, and they can be differentiated in lamellar and nonlamellar mesophases. Lamellar aggregates are characterized by the presence of one or multiple bilayers which possess vesicular morphology at larger scale (um). Nonlamellar mesophases with exotic symmetries, such as cubic and hexagonal, are lyotropic liquid crystalline systems with specific inner ordering, and among the most interesting nonlamellar structures are the bicontinuous cubic phases. When these systems are in excess water conditions, dispersed nanosystems are obtained and termed liposomes and cubosomes, respectively. The versatility and biodegradability of these nanosystems makes them particularly suitable as carriers for orally administered drugs. Moreover, lipids to be used for formulation development can be obtained from a variety of natural sources and biomasses, to obtain nanovectors for bioactive molecules with high carrier-cargo and carrier-target compatibility. In this thesis work, lipid nanovectors were designed and prepared as biocompatible and biodegradable drug carriers for a commercially valuable antioxidant drug i. e. curcumin, whose therapeutic application is typically hindered by its poor water solubility, that was chosen as the designated natural antioxidant of interest for this investigation. Two other antioxidants i. e. α-tocopherol and piperine were used as adjuvants for curcumin since they are known to facilitate incorporation and co-administration by acting synergistically as bio-enhancers. These three antioxidants were then encapsulated in newly formulated lipid nanocarriers to improve their biodistribution and bioavailability. The design strategy adopted for these formulations involved the use of natural-derived building blocks by lipid extraction from two biomasses of the marine microalga Nannochloropsis sp., containing mostly either phospholipids or triglycerides. Two dispersed nanovector series with different supramolecular structure were thus obtained i. e. liposomes and cubosomes, respectively. The high surface-to-volume ratio and loading efficiency granted successful encapsulation of the guest molecules. These nanoformulations were extensively characterized both from the physico-chemical and functional viewpoint. The structure and morphology was studied by combination of Dynamic Light Scattering, Small Angle X-Ray Scattering and Cryogenic Transmission Electron Microscopy. The guest-carrier and guest-guest interactions, stability and cargo entrapment were investigated by spectroscopic (UV–Vis, Nuclear Magnetic Resonance) and calorimetric (Isothermal Titration Calorimetry) techniques. Finally, the functionality was studied with both chemical and biological approaches, in an integrated structure-function perspective.