Periodic Reporting for period 2 - HYMADE (Hybrid Drug Delivery Systems upon Mesoporous Materials, Self Assembled Therapeutics and Virosomes)
Reporting period: 2017-02-01 to 2019-01-31
Our comprehensive studies on self-assembly mechanisms yielded a deep understanding of how the different components of the delivery systems impacted the properties of the hybrid materials. Transport studies through polyelectrolyte multilayers, fundamental for understanding release of encapsulated drugs, were performed and modeled.
The biological fate of the hybrid drug delivery systems was studied in vitro and in vivo. For in vitro studies, the translocation of fluorescently labelled drug delivery vehicles was followed in cells using confocal laser scanning microscopy, and detailed cell uptake studies were performed with flow cytometry. A thorough evaluation of toxicological endpoints of the drug delivery vehicles was also conducted in vitro.
The biodistribution and biokinetics of radiolabelled vehicles were studied in rats in both healthy and triple negative breast cancer models using positron emission tomography (PET). These in vivo studies allowed us to assess the ability of drug delivery vehicles to target triple negative breast cancer tumors for potential diagnosis and treatment. Importantly, we showed that vehicles functionalized with a targeting peptide accumulated in early tumor lesions more than twice as efficiently as untargeted vehicles. Overall, in vitro and in vivo fate studies provided valuable insight into how hybrid materials are processed in biological matrixes, which is fundamental to evaluate their potential application in drug delivery for the diagnosis and treatment of diseases.
Finally, drug delivery systems for siRNA were tested in cell culture. We showed that the systems could successfully deliver siRNA to cells to effectively silence expression of green fluorescent protein. These studies demonstrate the potential utility of our systems for delivering genetic material for a range of biomedical applications.
Through achievement of the project’s communication, dissemination and training goals, HYMADE produced several open access publications in top journals including Advanced Functional Materials, Soft Matter, Biointerphases, Materials Science and Engineering C, and Oncotarget. HYMADE partners participated in several outreach activities and training events, and organized thematic workshops and a final project conference, where the main results of the project were presented.
HYMADE achieved 98% of the proposed secondments, fostering the exchange of nearly 60 researchers between European countries and partner countries outside of Europe. These exchanges have had a notable positive impact on the career paths of the researchers involved, and have strengthened international collaboration between all countries that participated in the project.