Chitosan based hydrogels for transmucosal drug delivery

The aim of this thesis was the formulation of new chitosan based delivery systems for transmucosal drug administration. Transmucosal routes, such as buccal, vaginal and nasal routes, allow the circumvention of the hepatic first pass metabolism and avoid the gastrointestinal chemical and enzymatic degradations. Moreover, transmucosal drug administration can allow to avoid pain or discomfort caused by injections, when drugs are administered through parenteral routes, thus increasing patient compliance. On the other side, the major disadvantage of transmucosal drug administration is represented by the presence of biological fluids and mucus that can remove drug systems from the application site, thus reducing the contact time between drug and mucosa and consequently, decreasing drug bioavailability. For this reason, in this study, the investigation of chitosan delivery systems as mucoadhesive formulations able to increase drugs residence time and to improve their bioavailability, was taken into account. In the paper 1, buccal films based on chitosan-gelatin complexes were prepared and loaded with propranolol hydrochloride. The complexes were characterized and studied in order to evaluate their physical- chemical properties and their ability to release the drug and to allow its permeation through buccal mucosa. In the paper 2, vaginal inserts based on chitosan/alginate complexes were formulated for local delivery of chlorhexidine digluconate. Tests to evaluate the interaction between the polymers and to study drug release properties were performed, as well as the determination of antimicrobial activity against the patogens responsible of vaginitis and candidosis. In the project 3, chitosan based nanoparticles containing cyclodextrin and other excipients, with the capacity to modify insulin bioavailabity were formulated for insulin nasal delivery. Nanoparticles were characterized in terms of size, stability and drug release. Moreover, in vivo tests were performed in order to study the hypoglycemic reduction in rats blood samples.

Glycerol oxidehydration to acrylic acid on complex mixed-metal oxides

The project of this Ph.D. thesis is based on a co-supervised collaboration between Università di Bologna, ALMA MATER STUDIORUM (Italy) and Instituto de Tecnología Química, Universitat Politècnica de València ITQ-UPV (Spain). This Ph.D. thesis is about the synthesis, characterization and catalytic testing of complex mixed-oxide catalysts mainly related to the family of Hexagonal Tungsten Bronzes (HTBs). These materials have been little explored as catalysts, although they have a great potential as multifunctional materials. Their peculiar acid properties can be coupled to other functionalities (e.g. redox sites) by isomorphous substitution of tungsten atoms with other transition metals such as vanadium, niobium and molybdenum. In this PhD thesis, it was demonstrated how it is possible to prepare substituted-HTBs by hydrothermal synthesis; these mixed-oxide were fully characterize by a number of physicochemical techniques such as XPS, HR-TEM, XAS etc. They were also used as catalysts for the one-pot glycerol oxidehydration to acrylic acid; this reaction might represent a viable chemical route to solve the important issue related to the co-production of glycerin along the biodiesel production chain. Acrylic acid yields as high as 51% were obtained and important structure-reactivity correlations were proved to govern the catalytic performance; only fine tuning of acid and redox properties as well as the in-framework presence of vanadium are fundamental to achieve noteworthy yields into the acid monomer. The overall results reported herein might represent an important contribution for future applications of HTBs in catalysis as well as a general guideline for a multifaceted approach for their physicochemical characterization.