Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - FutForm (Future Formulations: Developing Future Pharmaceuticals Through Advanced Analysis and Intersectoral Exchange)

Teaser

The estimated cost of getting a new medicine to market is now in excess of $2.6 billion. The pressure to provide cheaper, more effective medicines has led to a demand for approaches that reduce development times and enable key decisions to be made earlier in the development...

Summary

The estimated cost of getting a new medicine to market is now in excess of $2.6 billion. The pressure to provide cheaper, more effective medicines has led to a demand for approaches that reduce development times and enable key decisions to be made earlier in the development process (i.e. in order to avoid failures in the later, more expensive clinical stages of development). Recent research within the School of Pharmacy (University of Nottingham (UoN)) has focussed on the application of advanced surface analytical and biophysical tools to address this need. This project will build on this activity via an intersectoral researcher exchange program focussed on supporting future pharmaceutical formulations development.

The principal objective of FutForm is to translate the advanced analytical approaches developed within UoN, so that they become embedded into industrial practice for the development of future pharmaceutical processes and therapies. This will be achieved through a collaborative programme of 92 months of intersectoral researcher secondments with three small-medium enterprise (SME) companies, each with early stage innovative technologies in areas of importance, namely; enzyme formulations for improved cell isolation (Abiel s.r.l; Italy), nanoparticle platform formulations for oral and topical drug delivery (Inovapotek, Pharmaceutical Research and Development Lda; Portugal) and hydrogel formulations for cell-delivery (Hy2Care b.v.; Netherlands). The application of UoN approaches will provide new insight into physical properties and structure-activity relationships, to address key developmental requirements for each of the formulations underpinning these technologies. This, in turn, will enable acquisition of proof-of-concept data and optimization for future applications, including improved cell-based drug-screening and toxicity tests, new formulations for the oral and topical delivery of biopharmaceuticals and injectable therapies for cartilage repair.

Work performed

We have provided 11 researchers (to date) with an opportunity to acquire and blend a number of disciplines through a secondment to a different country and a different sector. Secondees also have, and will continue to gain the opportunity to develop important transferrable skills through a series of formal training activities and consortium workshops. The training and experience of the researchers seconded to the SME’s is equipping them with the knowledge and skills and insights into commercialization of academic research. Similarly the researchers that are seconded from the SMEs to UoN are gaining exposure to and utilizing state of the art approaches that would not be available within their company. Wider dissemination to the home beneficiary of knowledge gained by the secondees during secondment is supported through local presentations on their return.

Progress on our scientific objectives is summarized below:
(a) The generation of routine cell isolation protocols for improved drug screening and toxicity testing applications
The activities of ABIEL in FutForm are focused on the optimization of the isolation protocols of hepatocytes and cardiomyocytes from liver and heart, respectively. The production of recombinant collagenases, class I and class II separately, gave the possibility to generate a specific formulation of collagenases in association with a proteolytic enzyme, for each specific extraction process. Optimized protocols for cell extraction have already resulted from this activity and the benefits of the cell extraction process are currently being evaluated in research projects based at UoN that are focused on sensor development and drug-delivery.

(b) The development of new nanoparticle formulation/manufacturing methods for oral drug – delivery.
This activity has only recently commenced through a 2 month secondment from Inovapotek to UoN and is focussed on generating robust strategies for the manufacture of nano (and micro) particles with tunable properties.

(c) The evaluation and safety testing of new biomaterial nanoparticles for topical drug-delivery.
The activities of Inovapotek and UoN within FutForm have resulted in new protocols to produce and evaluate nanoparticles for transdermal drug-delivery, and new approaches to evaluate the delivery of actives to the skin (including vitamin C). The collaboration has increased awareness of the approaches employed for the evaluation of the clinical efficacy of such formulations in both partners, and importantly has revealed new opportunities for the application of UoN approaches for the analysis of skin and hair.

(d) The generation of optimized injectable hydrogel formulations for cartilage repair.
The activities of Hy2Care and UoN in this area have focussed on gaining an improved understanding of the key components of the hydrogel technology which Hy2Care are developing for cartilage repair. Improved characterization of the polymeric components and also the enzyme required for crosslinking, has already enabled optimization of the formulation. Recentsecondments have focussed on exploring how the presence of cells modifies the properties of the hydrogel.

Final results

The participation of UoN and the industrial SME partners in this consortium provides the project with a wealth of innovative research, world-class infrastructure and expertise in pharmaceutical development and analysis. There is coherence to the selection of partners and to the structure of project; commonality lies in the application of advanced analytical approaches from UoN to a pressing pharmaceutical need commensurate with their specialized commercial experience and market knowledge. For example, Abiel provides expertise on the development of formulations for cell isolation and tissue dissociation procedures, standardization of which is key to the successful use of cells for reliable early stage drug and formulation screening. The need for reliable standardized and safe cell-based models represents a major issue for the biopharmaceutical and advanced therapies and medical products (ATMP) industry. Inovapotek provides expertise in nanoparticle formulation and evaluation; nanoparticle formulation approaches are attracting considerable interest for the oral and topical delivery of drugs that are traditionally hard to deliver (e.g. poorly soluble and large biological macromolecules), but require significant optimization and safety testing before this goal can be realized. Hy2Care provide expertise in the development of hydrogel formulations for cell delivery. With the first stem-cell therapy now released on the European market (Holoclar), cell therapies are emerging as the next generation of biologic. Most approaches however remain in the early research/proof-of-concept phase of development and thus require rapid optimization prior to clinical evaluation.

FutForm will significantly push the frontiers with regards seeking state of the art analytical solutions to address pharmaceutical development requirements. The research and innovation outputs of FutForm will present significant scope for commercial exploitation within future therapeutic approaches, which will ultimately lead to new job creation in Europe. This will also inform and shape the continued development of the research undertaken and training given to researchers. In turn, this will improve the quality of the graduates and boost their employability in both the academic and non-academic sectors.

Website & more info

More info: http://www.nottingham.ac.uk/futformrise/.