Personalised Pulsatile Materials (PPM)
Lead Research Organisation:
Newcastle University
Department Name: Sch of Engineering
Abstract
The project aims to develop a ground-breaking class of materials: functional porous polymers able to expand and collapse their volume fully autonomously in a predesigned rhythm for a predesigned duration. The goal of this fellowship is to produce biocompatible rhythmic (pulsatile) materials for medical applications. In particular, for controlled/targeted drug delivery in chronopharmacotherapy to treat diseases with established oscillatory rhythms in their pathogenesis, e.g. arthritis (10 million people in UK), duodenal ulcers (1 in 10 people in UK), cancer (1 in 4 of all deaths in UK) and cardiovascular diseases (1 in 4 adults in UK). Also, for mechanoresponsive tissues (e.g. bone and the vascular system) in regenerative medicine to facilitate cell activity and the assembly of mechanically robust and biologically functional tissue (organs). The proposed methodology incorporates collaboration with BDD (http://www.bddpharma.com/) and internationally recognised academic partners. This will enhance progress, knowledge dissemination, mitigate risks and ensure the materials are suitable for end-user driven development of fit-for-purpose products, and will accelerate transfer of research outcomes to healthcare applications. The proposal is built on the ground-breaking discovery of chemical oscillators employing polymeric substrates (Chem Commun 2014) and in-depth studies of biocompatible intelligent hydrogels (Adv Mater Sci Eng 2015) resulting from CAF2009. The project duration is 2 years and the methodology has 3 work packages (WP). WP1 in collaboration with Professor Vancso's group, Twente University, addresses the synthesis and experimental validation of proof-of-principle autonomous polymeric materials. In WP2, in collaboration with BDD company, characterisation and validation of the materials is pursued to meet end-user needs and regulatory requirements. WP3 in collaboration with Professor Kolar-Anic's group, Belgrade University, focuses on the development of predictive physico-chemical models to aid experimental studies and facilitate the design of patient-tailored materials. The proposal is aligned with Healthcare Technologies Grand Challenges (Developing Future Therapies; Optimising Treatment) and Advanced Materials and Future Manufacturing Technologies areas of research.
Planned Impact
The proposed research is pioneering. Developing a new class of intelligent materials, namely rhythmic (pulsatile, oscillatory) materials, whilst academically significant, has the strong potential for applications leading to societal and economic gain worldwide. Oscillatory chemical reactions employing polymeric substrates are currently unique to the Novakovic research group and taking them from discovery to applications is timely and momentous. The outcome of the proposed research will open a new chapter in the area of nonlinear dynamics in chemical systems and offer new directions in materials science, pharmacotherapy and tissue engineering.
In the area of drug delivery a successful outcome will offer truly personalised, drug delivery on demand. The economic impact of a successful research outcome is enormous. Active Pharmaceutical Ingredients (API) are the core of drug manufacturing. The price of APIs is the main cost driver for manufacturing. Only a limited number of pharmaceutical companies have their own API manufacturing capabilities, and none of them can make all required APIs in-house. Technology that leads to the reduction of the amount of API needed in medication while increasing its efficiency guarantees a large economic effect.
The technological solutions proposed here have the strong potential to improve the quality of life for a large number of people and, importantly, enable solutions previously not possible. Proposed rhythmic materials would lead to reduced side effects of the drug delivered and offer truly personalised treatment regimes. An aging population can significantly benefit from reliable hands-free drug delivery technology that would further result in far less reliance on hospital care. This is of direct relevance to Government as it directly leads to reducing costs to the NHS due to less wastage and further reduced costs by lessening patient reliance on hospitals.
User engagement is strongly exercised in the research methodology by close collaboration with Bio-Images Drug Delivery (BDD) a specialist drug formulation company with keen interest in controlled drug delivery. BDD has extensive knowledge of the relevant areas in the field of pharmacotherapy, will take an active role in the proposed research and is perfectly positioned to move from the research project outcome to full application and full release of impact. While the research proposed is pre-clinical BDD is a key link to fast and meaningful development in line with current regulatory requirements and enhanced technology transfer. To secure knowledgeable engagement in addition to a first-hand understanding of the pharmaceutical industry and related processes, Novakovic will train in the area of Health Economics and GLP.
Academic project partners are in place (the Vancso Materials Science and Technology of Polymers research group, Netherlands and the Kolar-Anic Non-linear Dynamics research group, Serbia) to aid project progress and promptly take research outcomes to new directions increasing impact further. To aid worldwide academic impact prospective project outcomes have been discussed with other academic leads keen to "take up" and further accelerate the research outcomes (Arthritis Centre UK, Newcastle section - rhythmic materials as scaffolds for mechanoresponsive tissue; Kuksenok group, Clemson University - computational design of rhythmic materials).
To create long-lasting academic capability a strong accent is placed on training skilled researchers and staff from the Novakovic, Vancso and Kolar-Anic groups in this multidisciplinary area so all three groups gain capabilities previously not available to them.
As the development of novel medical methods and technologies is relevant to the whole of society, engagement and communication with the general public will be pursued and executed (talking to patient groups via Wellcome Trust, public lectures, media).
In the area of drug delivery a successful outcome will offer truly personalised, drug delivery on demand. The economic impact of a successful research outcome is enormous. Active Pharmaceutical Ingredients (API) are the core of drug manufacturing. The price of APIs is the main cost driver for manufacturing. Only a limited number of pharmaceutical companies have their own API manufacturing capabilities, and none of them can make all required APIs in-house. Technology that leads to the reduction of the amount of API needed in medication while increasing its efficiency guarantees a large economic effect.
The technological solutions proposed here have the strong potential to improve the quality of life for a large number of people and, importantly, enable solutions previously not possible. Proposed rhythmic materials would lead to reduced side effects of the drug delivered and offer truly personalised treatment regimes. An aging population can significantly benefit from reliable hands-free drug delivery technology that would further result in far less reliance on hospital care. This is of direct relevance to Government as it directly leads to reducing costs to the NHS due to less wastage and further reduced costs by lessening patient reliance on hospitals.
User engagement is strongly exercised in the research methodology by close collaboration with Bio-Images Drug Delivery (BDD) a specialist drug formulation company with keen interest in controlled drug delivery. BDD has extensive knowledge of the relevant areas in the field of pharmacotherapy, will take an active role in the proposed research and is perfectly positioned to move from the research project outcome to full application and full release of impact. While the research proposed is pre-clinical BDD is a key link to fast and meaningful development in line with current regulatory requirements and enhanced technology transfer. To secure knowledgeable engagement in addition to a first-hand understanding of the pharmaceutical industry and related processes, Novakovic will train in the area of Health Economics and GLP.
Academic project partners are in place (the Vancso Materials Science and Technology of Polymers research group, Netherlands and the Kolar-Anic Non-linear Dynamics research group, Serbia) to aid project progress and promptly take research outcomes to new directions increasing impact further. To aid worldwide academic impact prospective project outcomes have been discussed with other academic leads keen to "take up" and further accelerate the research outcomes (Arthritis Centre UK, Newcastle section - rhythmic materials as scaffolds for mechanoresponsive tissue; Kuksenok group, Clemson University - computational design of rhythmic materials).
To create long-lasting academic capability a strong accent is placed on training skilled researchers and staff from the Novakovic, Vancso and Kolar-Anic groups in this multidisciplinary area so all three groups gain capabilities previously not available to them.
As the development of novel medical methods and technologies is relevant to the whole of society, engagement and communication with the general public will be pursued and executed (talking to patient groups via Wellcome Trust, public lectures, media).
Organisations
- Newcastle University (Fellow, Lead Research Organisation)
- BDD Pharma Ltd (Collaboration)
- University of Twente (Collaboration)
- University of Belgrade (Collaboration)
- University of Belgrade (Project Partner)
- Bio-Images Drug Delivery (United Kingdom) (Project Partner)
- University of Twente (Project Partner)
People |
ORCID iD |
Katarina Novakovic (Principal Investigator / Fellow) |
Publications
Novakovic K
(2018)
Hydrogels - Recent Advances
Parker J
(2017)
The Effect of Temperature on Selectivity in the Oscillatory Mode of the Phenylacetylene Oxidative Carbonylation Reaction.
in Chemphyschem : a European journal of chemical physics and physical chemistry
Parker J
(2016)
Autonomous reorganization of the oscillatory phase in the PdI2 catalyzed phenylacetylene carbonylation reaction
in Reaction Kinetics, Mechanisms and Catalysis
Parker J
(2017)
The effect of using a methanol-water solvent mixture on pH oscillations in the palladium-catalyzed phenylacetylene oxidative carbonylation reaction
in Reaction Kinetics, Mechanisms and Catalysis
Vo N
(2020)
Poly(ethylene glycol)-interpenetrated genipin-crosslinked chitosan hydrogels: Structure, pH responsiveness, gelation kinetics, and rheology
in Journal of Applied Polymer Science
Vo N
(2021)
Genipin-crosslinked chitosan hydrogels: Preliminary evaluation of the in vitro biocompatibility and biodegradation
in Journal of Applied Polymer Science
Vukajlovic D
(2019)
Chitosan based polymer/bioglass composites for tissue engineering applications.
in Materials science & engineering. C, Materials for biological applications
Vukajlovic D
(2021)
Fabrication and characterization of two types of bone composites made of chitosan-genipin hydrogel and Bioglass 45S5
in Open Ceramics
Description | The project aims to develop a ground-breaking class of materials: functional porous polymers able to expand and collapse their volume fully autonomously in a predesigned rhythm for a predesigned duration. The goal of this fellowship is to produce biocompatible rhythmic (pulsatile) materials for medical applications. In particular, for controlled/targeted drug delivery in chronopharmacotherapy to treat diseases with established oscillatory rhythms in their pathogenesis, e.g. arthritis, duodenal ulcers, cancer and cardiovascular diseases. To achieve this goal we have : - Developed organic oscillatory chemical reaction employing polymeric substrate - we are first, and only, research group that has achieved this. - Developer range of viable polymeric catalysts for our organic oscillatory reaction (again we are first to have done this) - Most importantly we have produced proof of concept oscillatory material and shown its potential in pulsatile drug delivery using model drug. Patent has been submitted and these findings are now published. This is truly ground-breaking achievement. |
Exploitation Route | Result we obtained is first of its kind. Patent is submitted to secure work with industrial partners in near future. Equally as achieved results opened amazing prospects in the area of nonlinear dynamics in chemical systems further research is to follow and many in the area will be influenced and motivated to pursue research in this direction. |
Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
URL | https://gtr.ukri.org/projects?ref=EP%2FN033655%2F1 |
Description | ESRF Grenoble |
Amount | € 5,000 (EUR) |
Funding ID | MA-3855 |
Organisation | National Synchrotron Radiation Research Center |
Sector | Public |
Country | Taiwan, Province of China |
Start | 01/2018 |
End | 02/2018 |
Description | Precisely-controlled drug delivery device for complex dosing regimens |
Amount | £49,957 (GBP) |
Funding ID | NU-002071 |
Organisation | Newcastle University |
Sector | Academic/University |
Country | United Kingdom |
Start | 11/2019 |
End | 04/2021 |
Description | Transdermal device for hands-free drug delivery in human and veterinary medicine |
Amount | £49,591 (GBP) |
Funding ID | OSR/0246/NACC/0001 |
Organisation | Newcastle University |
Sector | Academic/University |
Country | United Kingdom |
Start | 02/2020 |
End | 07/2021 |
Description | BDD Pharma |
Organisation | BDD Pharma Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | This is active collaboration where we are to lead in new drug delivery technology. |
Collaborator Contribution | BDD is contributing from the manufacturer angle guiding and providing advise on scale up and pathway to market. |
Impact | Main output is in knowledgeable direction we are talking in our research. |
Start Year | 2016 |
Description | Belgrade University |
Organisation | University of Belgrade |
Country | Serbia |
Sector | Academic/University |
PI Contribution | My research groups is providing oscillatory substrate date and taking part in joint mathematical modelling exercise. |
Collaborator Contribution | So far 2 researches from Belgrade group spend several month working in my group. Main contribution so far is in Stoichiometric Network Analysis of proposed reaction networks. |
Impact | Joint publications are starting to emerge. plans for further funding are ongoing. |
Start Year | 2016 |
Description | Twente University, Holland |
Organisation | University of Twente |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Ongoing collaboration with professor Julius Vancso's research group, Twente University, Holland. Key collaboration is in optical screening of hydrogel changes in situ as well as assessment of metallopolymers synthesised in Vanco group for application with oscillatory chemical reactions. |
Collaborator Contribution | Professor Vancso group is synthesising materials. |
Impact | Prof Vancso made in kind contribution with range of facilities my group can use at Twente University. Also with time. |
Start Year | 2016 |
Title | OSCILLATORY GELS |
Description | This invention relates to gels that undergo either oscillatory stepwise expansion or oscillatory expansion and contraction. An oscillatory reaction occurs within the gel, changing the conditions of the gel, and causing the gel to expand and optionally contract. The gels may be used for oscillatory release of a chemical agent. |
IP Reference | WO2020002909 |
Protection | Patent application published |
Year Protection Granted | 2020 |
Licensed | No |
Impact | The patent claims the composition of a series of hydrogels which release their content in a pulsatile manner. This current technology is the first to demonstrate pulsatile release of a cargo from hydrogels using an internal mechanism that is independent of external stimuli. Currently we are pursuing drug delivery devices employing these pulsatile materials. Recent work attracted further finding, including EPSRC IAA and Newcastle University internal funding. |
Description | CPACT research day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Personal invitation to deliver talk and meet with range of participants (industry and academia) at CPACT research day. |
Year(s) Of Engagement Activity | 2019 |
URL | https://cpact.com |
Description | Engaging with Charities |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Engaging with relevant charity representatives to learn first hand what are the main penitent needs. |
Year(s) Of Engagement Activity | 2017 |
Description | Fellowship Event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | Sharing experience of winning and holding fellowships. Delivering talk followed by Q and A session. Audience were postdocs and junior academic staff. |
Year(s) Of Engagement Activity | 2019 |
Description | Fellowship Seminar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Early career event. I was invited to share my experience of winning and holding EPSRC fellowships. |
Year(s) Of Engagement Activity | 2018 |
Description | Invited talk at Shefield University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Invited to give overview of the area and share insight into the future directions. |
Year(s) Of Engagement Activity | 2016 |
Description | Royal Academy of Engineering - North East Regional Event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Event was aimed at raising awareness of the Royal Academy of Engineering, sharing information on how to become a Fellow of the Royal Academy of Engineering, learning which funding is available from the Royal Academy and learning about some research carried out with Academy funding. I was invited to give research talk. |
Year(s) Of Engagement Activity | 2019 |
Description | Summer School Ameland |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | A summer school in the Netherlands on the Frisian Island Ameland on the topic "Smart Materials". I was invited lecturer that contributed to the program. This Summer School is offered by the Dutch Center on High Tech Materials of the Technical Universities (4TU.HTM; see: https://www.4tu.nl/htm/en/) and by the three National PhD Graduate Schools MESA+ (Twente), Zernike (Groningen) and Nijmegen Materials. |
Year(s) Of Engagement Activity | 2017 |
URL | https://www.4tu.nl/htm/en/events/ameland-summer-school-smart-materials/ |