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/