AMPHIPHILIC, BIODEGRADABLE ANDBIOCOMPATIBLE POLYMERS FOR INDUSTRIALAPPLICATIONS
Creators: name: CAPUANO, GIOVANNA
Publisher: name: Universit� degli Studi di Milano
Year: 2017

description: The aim of this PhD work was to establish the synthetic procedures for new families of biocompatible and biodegradable and/or bioeliminable biomaterials that can be differently processed to obtain nanoparticles, core-shell nanofibres and hydrogel slabs or conduits, respectively. Depending on composition, size and morphology, these biomaterials may be intended for applications as drug delivery systems and/or tissue regeneration. 
Specifically, the research project has been developed along two main lines:
? Synthesis of poly(lactic-glycolic acid)-g-poly(1-vinylpyrrolidin-2-one) (PLGA-g-PVP) copolymers whose architecture consisted of a long PLGA backbone with oligomeric PVP pendants. These were obtained by the radical polymerisation of 1-vinylpyrrolidin-2-one in molten PLGA 50:50, acting as chain transfer agent. The procedure was a single pot - single step one. Copolymers were characterized by FTIR, 1H- and 13C-NMR and thermal analyses. They were saponified giving, besides PLGA degradation products, also un-degraded PVP. This was isolated and analysed by size exclusion chromatography, to evaluate the molecular weights of grafted PVP chains. MALDI-TOF analysis allowed identifying the chemical structure of PVP terminals and unambiguously establishing that PVP chains had been grafted onto PLGA backbone
PLGA-g-PVP with different PVP content were formulated as drug nanocarriers by different procedures. Doxorubicin-loaded nanoparticles were prepared by the solvent diffusion method and fully characterised. In vitro drug release kinetics were studied and in vitro biological activity evaluated on several antitumoral cell lines.
PLGA-g-PVP were also used as coatings of lipid nanocapsules for the delivery of curcumin and artemisinin as antimalarials. Drug loaded-lipid micro-dispersions were first prepared by oil in water emulsion. The lipid drops were converted into nanometric ones by high pressure homogenization and finally surface coated by adding a DMSO/acetone PLGA-g-PVP solution. Growth inhibition assay were conducted on plasmodium falciparum (3D7) cultures. Haemoltic assays were conducted on healthy red blood cells.
PLGA-g-PVP- and PLGA-based scaffolds consisting of nanofibrous mats were produced by electrospinning. Starting materials were electrospun and their morphology was evaluated by scanning electron microscopy and wettability by contact angle measurements. Coaxial electrospinning of two materials, in which PLGA formed the core and PLGA-g-PVP the shell of fibres, were also conducted and compared with those obtained by mixed solutions of staritng materials. Chemical composition was evaluated by TGA, morphology by scanning electron microscopy and wettability by contact angle measurements. Nanofabric scaffold produced will be evaluated for drug release and tissue engineering applications.

? Synthesis of a new classes of poly(saccharide)-poly(aminoamine)s 3D-network intended as scaffolds for the regeneration of liver. 
In particular, hyaluronic acid-polyamidoamine and hyaluronic acid-gelatin- polyamidoamine hydrogels were synthesised by amidation reaction between the carboxylic acid group of hyaluronic acid and amine groups of gelatin and or an NH2-functionalized PAA, promoted by 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as coupling agent. Chemical-physical characterization were carried out on hydrogels. In order to promote hepatic cell proliferation serotonin was bonded to both hydrogels, adding it to the initial recipe, exploiting the above reaction between carboxylic acid group of hyaluronic acid and amine group of serotonin. Serotonin-loaded hydrogels were tested in vitro to evaluate biological efficacy.