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Digital archive of theses discussed at the University of Pisa


Thesis etd-02192010-161854

Thesis type
Tesi di dottorato di ricerca
Thesis title
Micro-Nanostructured Polymeric Constructs for Biomedical and Pharmaceutical Applications. Preparation and Chemical & Biological Evaluation
Academic discipline
Course of study
tutor Prof. Chiellini, Emo
  • Biomaterials
  • Dead Sea Salts
  • Oxygen Carriers
  • Polymeric Nanoparticles
Graduation session start date
Release date
Controlled drug delivery technology represents one of the most rapidly advancing areas of science in which several disciplines, such as chemistry, pharmaceutical technology, and medicine are contributing to human health care. The goal of drug delivery systems, is to deploy medications intact to specifically targeted organs and compartments of the body through a medium that can control administration of the active principle by means of either a physiological or chemical trigger. During the past decade, polymeric micro-nanoparticles, polymer micelles, and hydrogel-type materials have all been shown to be effective in enhancing drug targeting specificity, lowering systemic drug toxicity, improving treatment absorption rates, and providing protection for pharmaceuticals against biochemical degradation. The research activities reported in the present thesis are the result of experimental work performed at the Laboratory of Polymeric Materials for Biomedical and Environmental Applications (Biolab) of the Department of Chemistry and Industrial Chemistry of the University of Pisa and in part at SINTEF company (Trondheim, Norway). The aim of the present PhD thesis was mainly focused on the preparation of polymeric nanoparticles based on Poly(maleic anhydride–alt–butyl vinyl ether) 5% grafted with methoxyPEG2000 and 95% grafted with 2-methoxyethanol (VAM41) loaded with human Hemoglobin to be used as artificial oxygen carriers. Nanoparticles were prepared by means of the co-precipitation technique performed under controlled conditions in order to minimize oxidative phenomena; nanoparticles characterization was carried out in terms of size, morphology and surface properties analysis, highlighting the feasibility of obtaining Hemoglobin loaded polymeric nanoparticles possessing suitable features to be used as artificial oxygen carriers. The maintenance of protein functional bioactivities, once loaded inside nanoparticles, was also investigated; results showed that although protein secondary and quaternary structure seems to be maintained, Hemoglobin oxidation takes place during the formulation process. To overcome this inactivating phenomenon different strategies were investigated including the introduction of several reducing agents inside the formulation system as well as the modification of the polymeric structure by means of the introduction of a conductive moiety. Although Hemoglobin oxidation phenomenon during the formulation process was not avoided, alterations regarding nanoparticles features were not observed, highlighting the versatility of the so developed system and opening promising perspectives in the development of VAM41 based polymeric nanoparticles loaded with functional Hemoglobin. The use of Alginate as alternative polymeric matrix was also investigated; the formulation process based on the ionic gelation was optimised carrying out successfully the reduction of Alginate particles dimensions from a millimetric to a micrometric scale, without affecting particle protein contents. Results obtained during this research activity indicated Alginate as a potential polymeric matrix usable in the development of artificial oxygen carriers.
Moreover, during a six months visiting period spent at SINTEF, the research activity was focused on the development of VAM41 based polymeric nanoparticles loaded with Dead Sea Salts, to be used as dermal drug delivery system. VAM41 polymer was applied in a water-in-oil mini-emulsion based formulation system, demonstrating the feasibility of obtaining polymeric nanoparticles loaded with Dead Sea Salts possessing suitable features in terms of size and morphology; a time controlled release profile of the loaded active principle was also detected, opening promising perspectives in the use of the so developed system in topical pharmaceutical applications.