Bio-surfactants-based lipid architectures as nanomedicine platforms

The use of nanocarriers for drug delivery and imaging purposes have highly increased in the last decades. Both hard and soft matter-based formulations can provide selective and efficient treatment in several administration routes. Indeed, the biocompatibility and the biodegradability of the formulations represent a key requirement in order to translate the in vitro studies into in vivo investigations. Therefore, lipids are a safe choice as building blocks to formulate a large variety of liquid crystalline architectures in water. Vesicles, hexosomes and cubosomes have been adopted as nanomedicine platforms providing excellent biological performances. However, several drawbacks may impact the application of these carriers: the poor stability in the physiological environment and the biodegradability of the stabilizing agent required to sterically stabilized the nanoparticles (NPs) are few examples. Given the importance these materials have acquired nowadays in the nanomedicine field, this thesis is devoted to investigating on the factors that can enhance the physico-chemical and biological performances of these nanoparticles for systemic and topical administration. Most of the formulations presented in this thesis were prepared using monoolein as building block, given its biocompatibility and lower cytotoxicity in comparison with other surfactants. However, the potential application of cell-derived nanoparticles known as nanoerythrosomes for medical imaging was also explored. Therefore, the thesis evaluated different approaches: (i) evaluation of the effect of various stabilizers (modified poloxamers, hemicellulose and polyphosphoesters) on monoolein-based cubosomes features, in order to formulate nanoparticles suitable for systemic administration. This investigation was focused on the physico-chemical (bulk and surface) characterization of the empty carriers and of those loaded with antioxidants or fluorophores suitable for in vitro imaging. Bioassays (viability and uptake experiments) were conducted in order to evaluate the biological performance of the differently stabilized cubosomes. (ii) the effect of permeation enhancers and edge activators on monoolein-based vesicles and hexosomes for topical administration. In vitro permeation tests were performed to show the efficacy of these carriers into overcoming the stratum corneum, the first layer of the skin, to deliver antioxidants. (iii) the potential role of nanoparticles derived from red blood cells, nanoerythrosomes, as personal medicine for application in optical imaging. Cross-linking and Click Chemistry were employed to decorate the surface of the nanoparticles and their emission properties in a physiological buffer were evaluate.