Studies of different administration routes of engineered colloidal nanoparticles

The aim of my PhD work is to investigate the destiny of different kind of engineered colloidal nanoparticles (NPs) administered by different administration routes. The administration routes that I have investigated in my work are the topical, oral, inhalational and the intravenous administration. To investigate the topical route my purpose is to design and develop iron oxide nanoparticles coated with an amphiphilic polymer and formulated in highly stable suspensions or incorporated into semi-solids, to cross the skin in order to be used for loco-regional therapeutic treatments. Once the NPs suspension skin passage is assessed, the nanoparticles are loaded into different semi-solid formulations to test the possible NPs permeation improvement. In vitro experiments are performed on human abdominal skin and in vivo study in mice is set up to evaluate the NPs biodistribution after subcutaneous injection in comparison to topical administration. The results obtained in this study are promising for the development of nano-cream for the local skin treatment. As regard the second project several research studies have been focused on the development of novel formulations for the oral administration of insulin. I design insulin-containing nanoparticles that are loaded into pellet cores and orally administered to diabetic rats. The nanoparticles proposed are polyethylene imine-based nanoparticles and they are incorporated into pellets with two overlapping layers and a gastrointestinal film. The nanotechnology science and the knowledge of the solid pharmaceutical forms allow building a novel nanoformulation, multiple-unit colon release system, i.e. pellets, as a possible oral nanocarrier for insulin. The aim of the third project is a preliminary study of gold nanoparticles (GNPs) for the treatment of bronchiolitis obliterans syndrome (BOS). The GNPs are covered with an amphiphilic polymer and they are designed to be loaded with an immunosuppressant drug (everolimus) in the hydrophobic section and functionalized on the surface with a monoclonal antibody selective for the receptor expressed by mesenchymal cells, which are responsible of the pathology. This study confirms the capability of functionalized GNPs to be a selective and efficient drug delivery system and future perspectives interest the in vivo administration by inhalation of GNPs on animal models of obliterative bronchiolitis. As regard the last project I test iron oxide nanoparticles conjugated with a peptide by intravenous administration to improve the peptide passage to the central nervous system (CNS). It’s known that the blood brain barrier (BBB) is a poorly crossable endothelium by most drugs and for their inability to reach the CNS most are the neurodegenerative disorders, which don’t have effective therapies. For this reason iron oxide nanoparticles represent a promising vector for the peptide translocation across the BBB.