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Future Formulations: Developing Future Pharmaceuticals Through Advanced Analysis and Intersectoral Exchange

Deliverables

Summary report on hydrogel structure-activity relationships

This deliverable will be acheived through: Secondment activities at Hy2Care that will focus on the performance of industry standard tests (biocompatibility, toxicity etc) (Task 5.2) and safety and performance testing in orthotopic animal models (Task 5.3). Secondment activities at UoN that will focus on advanced characterization of the hydrogels to complement the studies performed at Hy2Care and to allow hydrogel optimization. Characterization will include high-resolution microscopy to determine cross-linking density (e.g. AFM/TEM imaging) (Task 5.4), combined with spectroscopy (FT-IR/FT-Raman) and AFM nanoindentation measurements (Task 5.5) to verify chemical and mechanical changes during cross-linking respectively. Later studies will employ surface chemical methods (e.g. TofSIMs, XPS) to define the chemical nature of cell-hydrogel and hydrogel- bone/cartilage interface (Task 5.6) alongside confocal fluorescence microscopy to understand the interaction with and effect on cells.

Generation of ISO 1345 Quality Management System

This deliverable will be acheived through secondments at Hy2Care which will focus on activities associated with product manufacture. Although product manufacture under cGMP conditions will be outsourced, the secondee(s) will be required to develop an ISO13485 quality management system to underpin this activity.

Standardized protocols for the formulation of tunable nanoparticles with defined properties

WP 3 aims to explore the potential of new nanoparticle manufacturing methods. This deliverable will be achieved through: Task 3.1 & Task 3.3 - The production, in-vitro characterization (size, morphology, drug loading efficiency) and optimization of nanoparticles loaded with drugs of different solubility and permeability properties (e.g. selected from the 4 classes of the Biopharmaceutical Classification System (BCS) for poorly soluble model drugs). Test formulations for model biopharmaceuticals (e.g. insulin) will also be prepared and characterized.

Standardized protocols for the formulation of nanoparticles with defined properties

This deliverable will be achieved through: Task 4.1 - the production and in vitro performance testing of a range of nanoparticle delivery systems (containing vitamin A) Task 4.2 - Characterisation of the resulting nanoparticulate formulations by AFM, ToF-SIMS, SEM and other analysis techniques.

Standardized SOPs for the optimized isolation of different cell types

This deliverable will be acheived by : Task 2.1 - optimization of primary and stem cell isolation protocols from tissues (e.g. adipose derived stem cells, cardiomyocytes, chondrocytes, osteoblasts, hepatocytes, pancreatic islets and fibroblasts) using formulations of specific collagenase class I/II ratios and of protease amount/type (thermolysin, dispase, pronase); Task 2.2 – evaluation of new biomarine enzyme formulations currently under development at Abiel; Task 2.3 – assessment of the reproducibility of results (e.g. cell yield, viability and functionality) and comparison to current standard isolation procedures (e.g. via commercial competitor products).

FutForm Showcase event

The Project Management Board will organise events to foster knowledge transfer and networking. This will include a Showcase event organized towards the end of the project (Month 40) to present and disseminate its research highlights and successes, and support further networking activities.

Academic, Industry networking meeting

The Project Management Board will organise events to foster knowledge transfer and networking. These will include an academic-industry knowledge sharing workshop (month 18).

Consortium agreement signed

This deliverable will be achieved as follows: Task 1: The coordinator will ensure all partners are aware of FutForm operational management requirements. Task 3: Compilation, collation and distribution of consortium documentation. The coordinator (assisted by the FutForm project manager) will be responsible for the compilation, collation and distribution of all consortium documentation in relation to operational management and in particular the research secondments.

Outreach event

The Project Management Board will oversee all aspects of dissemination and outreach to including showcasing the importance of these developments for pharmaceutical research to the general public via events such as the UoN MayFest Community Open Day.

Optimized nanoparticle formulations for topical delivery

This deliverable will be achieved through: Task 4.1 production and in vitro performance testing of a range of nanoparticle delivery systems (containing vitamin A) Task 4.2 (to UoN) Characterisation of the resulting nanoparticulate formulations by AFM, ToF-SIMS, SEM and other analysis techniques Task 4.3 Franz cell (ex vivo) and skin model (in vivo) testing of the developed formulations (to investigate permeation, potential safety issues etc) Task 4.4 Physicochemical analysis of samples from ex vivo and in vivo permeation studies to determine permeation properties, such as depth and localisation.

Proof of concept data to demonstrate the advantages of Abiel technology for drug/toxicity screening applications

The deliverable will be acheived by characterization of the formulations and the performance of cells within screening applications as follows: Task 2.4 – characterization of formulations through biophysical assay (e.g. AFM imaging based collagenase degradation studies; assessments of protein aggregation vs activity (e.g. AFM supported by other particle sizing approaches available at UoN); Task 2.5 – the building of 3D printed cell scaffolds yielding organotypic tissues grown from cells isolated using the Abiel technology, and standard procedures.Generated scaffolds will be used to monitor cellular behaviour at pinpoint location on the scaffold surface in response to well-known drugs and toxins (e.g. doxorubicin, troglitazone, quinidine and cobalt chloride).

Data to support the attainment of the European CE mark by Hy2Care

The data required to achieve this deliverable will be obtained through: Secondment activities at Hy2Care that will focus on the performance of industry standard tests (biocompatibility, toxicity etc) (Task 5.2) and safety and performance testing in orthotopic animal models (Task 5.3). Secondment activities at UoN that will focus on advanced characterization of the hydrogels to complement the studies performed at Hy2Care and to allow hydrogel optimization. Characterization will include high-resolution microscopy to determine cross-linking density (e.g. AFM/TEM imaging) (Task 5.4), combined with spectroscopy (FT-IR/FT-Raman) and AFM nanoindentation measurements (Task 5.5) to verify chemical and mechanical changes during cross-linking respectively. Later studies will employ surface chemical methods (e.g. TofSIMs, XPS) to define the chemical nature of cell-hydrogel and hydrogel- bone/cartilage interface (Task 5.6) alongside confocal fluorescence microscopy to understand the interaction with and effect on cells.

An optimized, tunable nanoparticle platform formulation for oral delivery applications

This deliverable will be acheived through: Task 3.1 & Task 3.3 - The production, in-vitro characterization (size, morphology, drug loading efficiency) and optimization of nanoparticles loaded with drugs of different solubility and permeability properties (e.g. selected from the 4 classes of the Biopharmaceutical Classification System (BCS) for poorly soluble model drugs). Test formulations for model biopharmaceuticals (e.g. insulin) will also be prepared and characterized. Task 3.2 & Task 3.4 - in-vitro drug release studies and in-house cell models to study intestinal adsorption.

FutForm Website up and running

The Coordinator will set up a website to support documentation for each secondment undertaken and dissemination of the resultant activities. The coordinator will also ensure the FutForm website provides up to date information regarding secondments (practicalities, outcomes, documentation etc) and training opportunities.

Publications

Isolation of Adult Rat Cardiomyocytes Using Recombinant Collagenases

Author(s): Simona Campora, Paola Sanjuan Alberte, Carmelo Bruno, Giulio Ghersi
Published in: CHEMICAL ENGINEERING TRANSACTIONS, 2018, ISSN 2283-9216
DOI: 10.3303/CET1864005

An injectable platelet lysate-hyaluronic acid hydrogel supports cellular activities and induces chondrogenesis of encapsulated mesenchymal stem cells

Author(s): Elaheh Jooybar, Mohammad J. Abdekhodaie, Mansour Alvi, Abbas Mousavi, Marcel Karperien, Pieter J. Dijkstra
Published in: Acta Biomaterialia, 2018, ISSN 1742-7061
DOI: 10.1016/j.actbio.2018.10.031

Vibrio Proteases for Biomedical Applications: Modulating the Proteolytic Secretome of V. alginolyticus and V. parahaemolyticus for Improved Enzymes Production

Author(s): Monica Salamone, Aldo Nicosia, Giulio Ghersi, Marcello Tagliavia
Published in: Microorganisms, Issue 7/10, 2019, Page(s) 387, ISSN 2076-2607
DOI: 10.3390/microorganisms7100387

Neural Crest-Derived Chondrocytes Isolation for Tissue Engineering in Regenerative Medicine

Author(s): Monica Salamone, Salvatrice Rigogliuso, Aldo Nicosia, Marcello Tagliavia, Simona Campora, Paolo Cinà, Carmelo Bruno, Giulio Ghersi
Published in: Cells, Issue 9/4, 2020, Page(s) 962, ISSN 2073-4409
DOI: 10.3390/cells9040962

Multifunctional Bioinstructive 3D Architectures to Modulate Cellular Behavior


Published in: ISSN 1616-301X
DOI: 10.1002/adfm.201902016