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Harnessing materials for the development of
advanced respiratory therapeutics
Sally-Ann Cryan PhD, MPSI
School of Pharmacy & Tissue Engineering Research Group, RCSI
Trinity Centre for Biomedical Engineering, TCD
Drug Delivery & Pharmacoengineering Team
Device Engineering
Materials & Processing
Therapeutics
http://www.rcsi.ie/tissueengineering https://www.tcd.ie/bioengineering/
Designing & developing next generation medical technologies:
A convergence between biomedical engineering and pharmaceutical science
http://www.curamdevices.ie/ http://ambercentre.ie/
Respiratory drug delivery: potential actives
Locally acting:
Small molecules
o Rifampicin
Proteins/peptides
o Secretory leukocyte
inhibitor (rSLPI)
o Interferon-
o Muramyl dipeptide
o Anti-IgE Mab
o Cyclosporin A
Gene therapies
o pDNA
o siRNA/miRNA
o miRNA
Cell-based therapies
Systemically acting:
Insulin
Fentanyl
Oestrogen
Ergotamine
FSH
Calcitonin
hGH
Interferon-
Ribavirin
Heparin
Emerging Advanced Therapies: Challenges and
Opportunities from Delivery & Development Perspective
Pharmaceutical & Regulatory issues•Inefficient delivery•Expense & instability of biomolecules•Lack of licensed excipients•Inadequate screening tools•Multi-drug regimens
Biopharmaceutical issues
•Instability & rapid clearance in vivo
•Poor site-specific targeting
•Cell-type specific targeting
•Poor intracellular delivery
•Poor cell survival, engraftment and retention
•Toxicology and immunogenicity
•Poor IVIVIC
Device Engineering
Materials & Processing
Therapeutics
Translational Pharmaceutics for Respiratory TherapeuticsA convergence between biomedical engineering and pharmaceutical science
Device Engineering
Materials & Processing
Therapeutics
Areas of focus • Basic biomedical research
• Molecular pharmaceutics
• Advanced biomaterials & excipients development
• Cell models and tools for translation
• Applied research • Formulation of therapeutic cargoes• In vivo pre-clinical studies
• delivery, toxicology, pharmacokinetics• Implantable devices
• Industrial research/commercialisation• Product/platform development
• Optimising device performance and/or expanding applications
• Drug-device development & integration
Designing & developing next generation medical technologies:
A convergence between biomedical engineering and pharmaceutical science
Locally acting:
Small molecules
o Rifampicin
o atRA
Proteins/peptides
o Secretory leukocyte inhibitor
(rSLPI)
o Interferon-
o Muramyl dipeptide
o Anti-IgE Mab
o Cyclosporin A
Gene therapies
o pDNA
o siRNA/miRNA
o miRNA
Cell-based therapies
Systemically acting:
Insulin
Fentanyl
Oestrogen
Ergotamine
FSH
Calcitonin
hGH
Interferon-
Ribavirin
Heparin
Respiratory drug delivery: potential actives
Inhaled Therapies for Treatment of Tuberculosis
Inhaled proteins: liposome encapsulated rSPLI
rSLPI Transport in vitro: Calu-3 monolayer
rSLPI transport in vivo: guinea pig asthma model
Intracellular rSLPI
Inhaled gene therapies
Kelly et al 2012 RNAi for
Respiratory disease
polypeptide
nanoparticles
hydrogels
polymer
synthesis
star
polypeptides
Functionalised scaffolds
for Regenerative applications
Therapeutic aerosol
bioengineering
Materials for cell &
drug delivery to the lungs
Injectable Hydrogels for
minimally
invasive delivery
3D printing
Functional polymers for drug delivery & medical devices
Advanced
testing of lead
nanomedicines
In vitro
toxicology &
efficacy testing
Advanced
Materials
Development
Pharmaceutical
formulation &
characterisation
Nanoparticle-
Device
Integration
intubation stand
mixedshells
Star-miRNA
nanomedicine
Development of High
Content Screening
methods with UCD
Star polypeptide approaches for Respiratory Drug Delivery
Collagen-Hyaluronic Bilayered Scaffolds
Freeze-Dry
Advanced tools for Respiratory Drug Development: 3D Tissue Engineered Models
Co-culture of airway cells on the bilayered scaffolds
Potential Applications:
• Co-culture models
• Toxicity & immunogenicity (including nanotxicology)
• Disease models
• Regeneration
TREND Core Expertise & Application Areas
polypeptide
nanoparticles
hydrogels
polymer
synthesis
star
polypeptides
Development of GF-loaded scaffolds
for bone regeneration
Inhaled anti-inflammatory
Nanomedicines
Hydrogel scaffolds for cell &
drug delivery to the lungs
Hydrogel scaffolds for cardiac
regenerative medicine
3D printing
3D Printing: development of materials & tubular scaffolds
3D Printed tubular scaffolds
i) Tailored in structure to match a patient CT scan
ii) Materials & design chosen to provide mechanical
strength & ECM features
Materials for Health
• Drug formulation
• Drug-device combinations
• Nanomedicines
• Particle engineering
• Tissue engineering & 3D models for drug development
• Printable bioinks
MATERIALS
FOR HEALTH IMMUNOLOGY
NERVE & OCULAR REGENERATION
VASCULAR TISSUE ENGINEERING
CARDIOVASCULAR THERAPIES
TISSUE ENGINEERED IMPLANTS
BIOENGINEERED & GENE ACTIVATED SCAFFOLDS
Advanced Material and Bioengineering Research Centre
AcknowledgementsResearch Team:
Dr. Aileen Gibbons
Dr. Ciara Kelly
Dr. Joanne Ramsey
Dr. Alan Hibbitts
Dr. Cian O’Leary
Dr. David Walsh
Dr. Christina Payne
Dr. Gemma O’Connor
Dr. Alive McCloskey
Dr. Sarinj Fattah
Rachel Gaul
Luis Soriano
Respiratory Collaborators:
Prof. Andreas Heise (RCSI)
Prof. NG McElvaney & Prof. Catherine Greene (Beaumont& RCSI)
Prof. Joe Keane & Dr. Mary O’Sullivan (SJH)
Dr. Brian Robertson & Dr. Robert Endres (Imperial College London)
Prof. Clifford Taggart (QUB)
Prof. Anthony Hickey (UNC-Chapel Hil)
Dr Ronan MacLoughlin (Aerogen)
Dr. Michael Maguire (Avectas)
Prof. Fergal O’Brien (RCSI)
Acknowledgements
@trendmaterials1 @TissueEngDublin
http://rcsi.ie/tissueengineeringhttps://www.trendmaterials.com/