Final Report Summary - NANODRUG (Novel nanoparticles for drug delivery to the skin) The aim of the NANODRUG research training network was to develop and characterise a selected set of novel intelligent nanomaterials and to study their suitability as novel drug delivery systems targeting inflammatory skin diseases.The three scientific objectives of the project were: (i) development of nanomaterials as drug carrier; (ii) study of the drug – nanoparticle complexes; (iii) drug release and preclinical models.This project was made by six academic groups and two industrial teams as full partners, complemented by three associate partners, one of which is an industrial team, distributed over a total of six European Union member states and one non-ICPC country. The consortium brought together groups with a common scientific interests in the development and application of drug delivery systems targeting the skin. The scientific background was very interdisciplinary, with expertise ranging from polymer synthesis and characterisation, computational modelling and physicochemical characterisation of materials to bioavailability, nanoparticles formulation, drug distribution and nanotoxicity, genetics, drug delivery and clinical dermatology.Description of the work performed since the beginning of the project.Scientific work packagesWork Package 1 focused on the synthesis and characterization studies of the new nanoparticles. This part of the project was implemented to a large extent by three teams, QMUL, CNRS and MJR, including the other partner collaborations. All deliverables were successfully achieved for WP1.A variety of polymeric materials was developed since the last report. The optimisation of biocompatible nanoparticles loaded with antimicrobial peptide LL37 and with vascular endothelial growth factor were achieved, together with their characterisation in terms of size, encapsulation efficiency and release profile. The synthesis of stimuli-responsive nanoparticles and supramolecularly crosslinked nanogel led to the development of systems triggered by stimuli, such as pH and temperature, which were characterised displaying small size. Also novel fluorescent bio-inspired micelles were prepared, showing small size. For imaging purposes, UCP-UV nanoparticles were prepared and their behaviour was studied. Ultra-deformable and elastic liposomes and skin penetration evaluation, studied by MJR (D1.1) were judged satisfactory and not further developed. To complete the work in this WP1, computational studies for evaluating materials and drug interactions, developing a proper simulation model, were successfully carried out by SANOFI. Furthermore, the milestone 1.1 was also fully achieved.Work Package 2, fully dependent on the results in terms of NPs obtained in WP1, was a very collaborative research effort. Although MJR was the lead beneficiary, it was strongly supported by QMUL-1, CNRS, CNBC, CRAN and ULC. It focused on the development of drug-nanoparticles complexes focusing on two groups of targets: i) traditional anti-inflammatory drugs and ii) nucleic acids. In addition, there was the clear aim to evaluate the biocompatibility and toxicology not only of the nanoparticles obtained, but also of the prepared complexes, focusing on i) skin biocompatibility and toxicity; ii) systemic toxicity and iii) the mechanistic studies of the impact of nanoparticles on cell membranes. All the deliverables of WP2 were fully achieved with the exception of D2.6 which was partially achieved. The incorporation of small drugs into with a variety of different nanoparticles was successfully obtained, while the characterization of nanomaterials was conducted by assessing shape, dispersion, chemical composition and stability in water and culture medium. These techniques were used to characterize different types of nanomaterials to be supplied by partners before toxicology evaluation. The encapsulation efficiency obtained resulted good, in some cases as high as 90%. A great progress and interesting results were achieved by CNBC team on the formation of drug-nanoparticles complexes for small nucleic acid. The optimization of the protocols of drug incorporation and nanoparticle characterisations were functional to the studies on skin, both for cytotoxicity and permeability carried out in WP3. Moreover, biocompatibility and toxicity data obtained by the teams were used to enhance the systems design. In addition, the toxicity/cell uptake profile of polymer NPs produced at QMUL have been studied at CRAN and the results proved useful for improvement of NP design for cellular targeting. Important improvements were also achieved by UIBK on the computational modelling of nanoparticles mimicking the interaction with lipid membranes.The research on Work Package 3 substantially improved during the last period, partially achieving all the deliverables. Only D3.2 - D3.4 did not start because no end formulations were prepared by the teams. A very collaborative activity led to substantial progress on the scientific activities from QMUL, with the identification of new skin disease genes or inflammatory skin diseases including syndromic disease with inflammatory bowel or oeosphageal cancer and also for the more common skin disease, atopic eczema. Also MJR contributed on the preparation of superparamagnetic iron oxide nanoparticles that have diverse diagnostic and potential therapeutic applications. In the case of glioblastoma they were useful for diagnostics using MRT, for chemotherapy, hyperthermia treatment and for drug targeting. More experiments aimed to test the permeation of NPs through the skin, but partial results were achieved. Work Package 4. The trainings and transfer of knowledge program detailed in Annex I was followed and all of the Network events planned were achieved. The 5th International Scientific Meeting took place in June 2015 (month 44) to discuss the latest results and consolidate future collaborations. The inter-sectorial secondments of researchers, between academic teams and the industrial partners, were achieved although they were slightly delayed according to the scheduled plan agreed by the Supervisory board. The fellows have enjoyed living and working in a different country. They have consolidated their professional and personal friendship to each other and there have been a lot of exchanges at all levels.A number of scientific trainings were attended at local level, either during their secondment or during their contract (for the ERs employed by the teams) by all the fellows as part of the professional development scheme. Work Package 5: management. A regular and very effective communication between teams which was a key component for the successful planning of the project delivery. The exchange and dissemination of scientific results and meetings between PIs made it easy for the Coordinator to monitor the progress of the project and to plan future collaborations and secondments. The superb collaborative work regarding the organization of events has been so efficient that allowed to plan two Summer/Winter Schools and three International Meetings within one year (July 2014 – July 2015). The website was a useful tool for disseminating information and documents to all PIs and Fellows. The project deliverables have all been achieved. The change of the Network Administrator did not affect the standard of communication and organization within the Consortium.Work Package 6: Output, dissemination and outreach activities. The network website (www.nanodrug.qmul.ac.uk) has been constantly updated and the newsletters were published on the website every 4 months. The teams have been very proactive in disseminating results. The NANODRUG teams have given 14 oral communications and presented 26 posters at 40 national and international events. 12 papers have been published in peer-reviewed scientific journals together with 2 book chapters. An important part of the NANODRUG activities has been the outreach. Most teams have reported a very healthy program of activities implemented either by the PIs or the fellows. The outreach has focused on the organisation of outside events, like helping with Science Days in schools, giving career and scientific talks, and hosting these events locally, within the institution or the team laboratories. The target of audience has been very wide, going from primary school children aged 8 to 10 years old, to secondary school children aged 15 to 18 but also the more general public, including adults. The Coordinator of NANODRUG is a STEM ambassador (Science, Technology, Engineering and mathematics) and regularly takes part or organises events that are designed to promote science to the general public, but more specifically in schools.The scientific results achieved within NANODRUG demonstrated the contribution in the field of nanomedicine obtained by: i) development and characterisation of a selected set of novel intelligent nanomaterials; ii) study their suitability as novel drug delivery systems targeting inflammatory skin diseases. More information about the project can be found on the website: www.nanodrug.qmul.ac.uk
