Periodic Reporting for period 1 - IA-NANO (Albumin particles for intra-articular delivery of celecoxib to treat osteoarthritic inflammation.)
Période du rapport: 2019-08-01 au 2021-07-31
This project is important because it will attempt to reduce the side-effects that are associated with the commonly used medicine for OA i.e. Cel. Moreover, it will increase the bioavailability of the drug which will decrease the overall treatment cost. The NP that was developed in this project could potentially be loaded with drugs used for other indications like cancer and could have similar benefits of increased bioavailability, more efficacy, low side-effects, and reduced treatment cost.
The main objective of this project was to develop a Cel-loaded biocompatible NP and demonstrate its application for IA drug delivery of Cel to treat OA.
The other objectives of the project were:
1. To enhance the knowledge of the researcher in terms of technical, transferable, and complementary skills.
2. To enhance the host supervisor capacity in delivering nanomedicine projects.
3. To disseminate, communicate and exploit the results of the project.
In summary, the biocompatible Cel-loaded human serum albumin (HSA) NPs were successfully synthesised and characterised. The NPs reduced markers associated with inflammation in an activated human monocytic cell line (THP-1) and in primary chondrocytes from the knee joints of OA patients.
WP1: Management
The project was started by listing out and placing orders for all the chemicals and equipment required. As multiple institutes and departments were involved in the project, meetings were organised to discuss the project and its requirements, researcher training and access. IP management, ethics management and a data management plan were discussed and finalised with the respective institutes/departments.
WP2: Training and Knowledge Transfer
Many trainings were provided to the researcher to enhance her technical, complementary and transferrable skills. The researcher also transferred her knowledge on development and characterisation of NPs as outlined in the project proposal.
WP3: Development and characterisation of Cel-loaded HSA particles
The Cel-loaded HSA NPs of 2 different average sizes (~66 nm and ~351 nm) were synthesised and characterised using different spectroscopic, microscopic, and scattering techniques.
WP4: Cytotoxicity and anti-inflammatory efficacy study in vitro
The cell viability and anti-inflammatory efficacy of Cel-loaded HSA NPs of ~66 nm were assessed in activated THP-1 cells and in primary chondrocytes from OA patients.
WP5: Anti-inflammatory efficacy study using an ex vivo explant culture model
The anti-inflammatory efficacy of Cel-loaded HSA NPs of ~66 nm was assessed in ex vivo cartilage from the knee of OA patient.
WP6 – Dissemination, Exploitation and Communication
The possibility of filing a patent for the NP made in this project was discussed with NovaUCD and an external patent consultant. The researcher participated in the Commercialisation Bootcamp organised by NovaUCD. An invention disclosure form was submitted to NovaUCD. As a part of dissemination and communication activities, presentations were given on the project and the project results to groups at UCD and in the SFI-CURAM Centre. An article was published in ‘News Rheum’ Newsletter (7th edition). General awareness about the projects and the scholarship funded by EU was posted and tweeted in LinkedIn and Twitter respectively.
In summary, we synthesised Cel-loaded HSA NPs in a novel process without using cross-linking agents, high temperature, polymer coatings, oils and Class II solvents. The NPs were spherical, and the surface was smooth. The NPs also had a narrow size distribution and a low polydispersity index. The NPs showed sustained release of Cel in phosphate buffer. The NPs of size ~66 nm was found to be stable at both room temperature (RT) and 4 C. Moreover, the NPs (~66 nm in diameter) did not reduce cell viability in activated THP-1 cells or in primary chondrocytes from OA patients. The Cel-loaded HSA NPs also decreased the inflammatory markers produced in activated THP-1 cells line and in OA chondrocytes. The ex vivo studies indicated through imaging that the NPs were able to penetrate the dense collagen matrix of cartilage to target chondrocytes.
The HSA NPs of size less than 100 nm developed within this project may also be utilised to load anti-cancer drugs and can be used for passive targeting of cancer through the enhanced permeation and retention (EPR) effect.
OA and cancer are two of the twenty-four priority diseases quoted in the WHO report on ‘Priority Medicines for Europe and the World Update Report, 2013’ and finding a more effective treatment for these diseases are in line with ‘EU’s Horizon 2020 Programme focus area - Health, Demographic Change and Wellbeing and UN Sustainable Development goal - Good Health and Well-Being’.
The Cel-loaded HSA NPs developed in this project have the potential to be used for IA knee delivery of Cel for targeted OA treatment, which may have the potential for commercialisation and thus can be expected to reduce the total drug cost and adverse side effects, which in turn will decrease the economic burden and increase the good health and well-being.