STRUCTURE AND DYNAMICS OF CATANIONIC NANORESERVOIRS AND FUNCTIONAL HYDROGELS FOR BIOMEDICAL APPLICATIONS

Polymer-vesicles systems are peculiar colloidal mixtures of increasing interest, due to their ability to mimic biomembranes, suitability as drug/gene delivery carriers, as well as their employment in formulation of paints, cosmetics, shampoos, etc. Basically, the final purpose concerns a rational design of hydrogels formulation at high water content, based on biocompatible polymeric networks, with tunable characteristics. Thus, six different research branches have been examined: - vesicles characterization and optimization (chapter 2); - vesicles stabilization, thanks to a complexation with b-cyclodextrin (chapter 3); - surfactant-free gel (guar gum and borax ࢠchapter 4); - monosurfactant-driven gel (pluronic F127 and alginate ࢠchapter 5); - vesicles-driven gel-like systems, using two surfactant (chapter 6); - optimization of the mentioned composite systems, with catanionic vesicles and hydrophobically modified cellulose (chapter 7). Catanionic vesicles, in general, are originated by the association of two oppositely charged ionic surfactants in the presence of an excess of one of the two partners, for charge stabilization reasons. The main difference between catanionic vesicles and liposomes, the most famous aggregates of phospholipids, concerns their spontaneous formation. Furthermore, they offer the advantage of an infinite variety of starting materials, commonly cheaper and more reproducible than phospholipids, which gives the possibility of an easy tailoring of the self- assemblies properties. Catanionic vesicles are characterized by a thermally induced transition from multilamellar, polydisperse, spontaneously formed vesicles to unilamellar ones. Mixing a polyelectrolyte (i.e. a ionic charged polymer) with oppositely charged vesicles leads to a wide variety of associations, which depend on vesicle composition, size, concentration and charge, together with polymer flexibility, charge density and effect of the chain substitution. Vesicles complexation with b-cyclodextrins evidenced quite promising results for drug delivery applications, as vesicular nanoreservoirs can be stabilized thanks to a CMC increasing effect of ?-cyclodextrin, without occurrence of multiple phases. Experiments lead to conclude that, despite their ࢠsoftࢠnature, catanionic vesicles can successfully resist to the addition of saccharide-based molecules. Thus, preliminary studies concerning both strong and weak hydrogels were performed, as reference systems. The final step involved the inclusion of catanionic vesicles in a cellulose-based polymeric network. Polymeric hydrogels based on non-covalent interactions, compared to chemical-crosslinked ones, are characterized by the absence of harmful, secondary products of the cross-linking reaction and by reversibility, thus these materials can be promptly responsive to external stimuli. These features look interesting in the perspective of biomedical use. Highly diluted polymeric hydrogels can be achieved thanks to several non-covalent cross-linking methods: both electrostatic and hydrophobic interaction cooperate within these systems and their role is due to the specific chemical substances involved. Guar gum is a natural, inexpensive polymer, which is able to produce a highly viscous solution even at low concentrations, and therefore it is used in several fields, such as food, oil recovery and personal care; borax is considered an efficient crosslinker for polymers, bearing hydroxyl groups. The high viscosity of guar gum solutions is due to its high molecular weight (up to 2 million and further), as well as the presence of extensive intermolecular associations (entanglements), thanks to hydrogen bonds. In aqueous solution guar gum assumes a flexible coil conformation. Guar gum, crosslinked with glutaraldehyde, was proposed for colon delivery, and it was also tested as a matrix for oral solid dosage forms. Moreover, a composite hydrogel formed by Pluronic F127 and alginate in water, crossliked using divalent ions, was designed to address an in situ sustained delivery for innovative antiproliferative agents, employed to prevent coronary restenosis. Unfortunately, treated arteries may narrow again due to overproliferation of smooth muscle cells of the blood vessel wall (coronary restenosis); thus a solution can be constituted by antiproliferative agents such as innovative nucleic acid based drugs (NABD). The latter should be protected against enzymatic degradation and released constantly in the coronary artery for several months. So, an appropriate gel system has been designed, in order to line the coronary internal lumen by a drug loaded polymeric film. Later on, a peculiar kind of gel-like systems, made up of natural and renewable polymers, crosslinked thanks to an interactions with ionic charged vesicles, has been tailored for many drug delivery purposes. Currently, biopolymers and their derivatives are on stage as they are biocompatible, eco-friendly and biodegradable. Different types of cationic hydroxyethylcelluloses have been employed, considering they are highly biocompatible, cheap, possess antimicrobial activity, and therefore, widely used in personal care products, such as solutions for contact lenses and hair-care formulations. These peculiar systems provide a non-denaturing environment for novel drugs based on polypeptides and polynucleotides, due to their very high water content.