Duvall Lab Poster 2018
Advanced Therapeutics Laboratory Craig Duvall, Ph.D.
Associate Professor, Biomedical Engineering Vanderbilt University, Nashville, Tennessee, USA
Overview
Scaffolds and Cell Delivery NSF CAREER & NIH NIBIB R01
Local Delivery of siRNA Modulates Tissue Healing
ROS-Responsive Materials Match Degradation to Tissue Infiltration
Breast Cancer Therapies DOD BCRP & NIH NCI R01
The Advanced Therapeutics Laboratory focuses on the design and applications of novel polymer-based materials for drug delivery pH Responsive Hydrophobicity
Improved siRNA Polyplex Chemistries for In Vivo Gene Knockdown In Vivo Luciferase Knockdown
Thermal Gelation
Days
Local Degradation
Environmental Activation
siRNA Lipid Conjugates for Carrier-Free Gene Silencing
“Smart” polymers can respond to changes in temperature, pH, reactive oxygen species, enzymes, and more!
ROS-Shielding Hydrogels for Therapeutic Cell Delivery
“RAFT” Polymerization Allows Rational Design of Diverse Polymers RAFT Chain Transfer Reagent
Polymer
Monomer (M) Initiator
PDN Hydrogels Solidify Upon Heating
Allows Many Polymer Backbone Architectures
Defined End Groups for Pre- or PostPolymerization Conjugates = R Group
Osteoarthritis Therapies
= Z Group
Vascular Graft Therapies
DOD PRORP
NIH NHLBI R01
1 .5
Polymer-enhanced Peptide Drug Delivery Prevents Vascular Graft Failure Polymeric Materials to Tackle Multi-Scalar Drug Delivery Challenges
**
1 .0
Nanoparticle Formulation
Intracellular Delivery Cellular Internalization
pH-responsive Polymer
Gal8-YFP Reporter Cell
Glycan
Endosome
EndosomalMembrane Disrupted; Gal8 binds and induces punctate fluorescence
0 .5
pH-triggered Endosomal Escape
Therapeutic Peptide
Nanoparticles
for intracellular biologic drug delivery
Microspheres for local, controlled drug release
Vein graft harvest
PPS-MS
60 min
Surgical Implantation
Nanoparticle
Ex vivo treatment
Improved Graft Patency
Galectin-8 recruitment shows real time endosomal escape
Graft Copolymer Library for Structure-Function Characterization
(x107) 5
Cartilage Damage (CII680)
Endosome
0 min
Clinical Application
Scaffolds
for large tissue defects
Gal8
Peptide
No Tx
B a re N P
m A b C II N P
0 .0
Gal8-YFP Reporter Cell
YFP
Intra-articular Drug Delivery Treats Osteoarthritis 8 Saline
Emulsion
YFP Gal8
Antioxidant Microspheres Provide Local Sustained Drug Delivery
PPS Poly(Propylenesulfide)
Endosomal Membrane Intact; Gal8 binding blocked
Intracellular Release
+O A
Antioxidant Microspheres
Endosome Escape Screening
Electrostatic Complexation
*
No Tx
Intracellular Delivery of siRNA N o r m a liz e d
Targeted Accumulation in Joint Space
M M P - 1 3 E x p r e s s io n
Antibody Conjugated Nanoparticles Target Damaged Cartilage
CDMRP 11 Fellowships since 2010
BCRP & PRORP
PBS
Alkyl Side Chains Modulate pH-dependent Hemolysis
pAA
70:30 Octyl
Associate Professor, Biomedical Engineering Vanderbilt University, Nashville, Tennessee, USA
Overview
Scaffolds and Cell Delivery NSF CAREER & NIH NIBIB R01
Local Delivery of siRNA Modulates Tissue Healing
ROS-Responsive Materials Match Degradation to Tissue Infiltration
Breast Cancer Therapies DOD BCRP & NIH NCI R01
The Advanced Therapeutics Laboratory focuses on the design and applications of novel polymer-based materials for drug delivery pH Responsive Hydrophobicity
Improved siRNA Polyplex Chemistries for In Vivo Gene Knockdown In Vivo Luciferase Knockdown
Thermal Gelation
Days
Local Degradation
Environmental Activation
siRNA Lipid Conjugates for Carrier-Free Gene Silencing
“Smart” polymers can respond to changes in temperature, pH, reactive oxygen species, enzymes, and more!
ROS-Shielding Hydrogels for Therapeutic Cell Delivery
“RAFT” Polymerization Allows Rational Design of Diverse Polymers RAFT Chain Transfer Reagent
Polymer
Monomer (M) Initiator
PDN Hydrogels Solidify Upon Heating
Allows Many Polymer Backbone Architectures
Defined End Groups for Pre- or PostPolymerization Conjugates = R Group
Osteoarthritis Therapies
= Z Group
Vascular Graft Therapies
DOD PRORP
NIH NHLBI R01
1 .5
Polymer-enhanced Peptide Drug Delivery Prevents Vascular Graft Failure Polymeric Materials to Tackle Multi-Scalar Drug Delivery Challenges
**
1 .0
Nanoparticle Formulation
Intracellular Delivery Cellular Internalization
pH-responsive Polymer
Gal8-YFP Reporter Cell
Glycan
Endosome
EndosomalMembrane Disrupted; Gal8 binds and induces punctate fluorescence
0 .5
pH-triggered Endosomal Escape
Therapeutic Peptide
Nanoparticles
for intracellular biologic drug delivery
Microspheres for local, controlled drug release
Vein graft harvest
PPS-MS
60 min
Surgical Implantation
Nanoparticle
Ex vivo treatment
Improved Graft Patency
Galectin-8 recruitment shows real time endosomal escape
Graft Copolymer Library for Structure-Function Characterization
(x107) 5
Cartilage Damage (CII680)
Endosome
0 min
Clinical Application
Scaffolds
for large tissue defects
Gal8
Peptide
No Tx
B a re N P
m A b C II N P
0 .0
Gal8-YFP Reporter Cell
YFP
Intra-articular Drug Delivery Treats Osteoarthritis 8 Saline
Emulsion
YFP Gal8
Antioxidant Microspheres Provide Local Sustained Drug Delivery
PPS Poly(Propylenesulfide)
Endosomal Membrane Intact; Gal8 binding blocked
Intracellular Release
+O A
Antioxidant Microspheres
Endosome Escape Screening
Electrostatic Complexation
*
No Tx
Intracellular Delivery of siRNA N o r m a liz e d
Targeted Accumulation in Joint Space
M M P - 1 3 E x p r e s s io n
Antibody Conjugated Nanoparticles Target Damaged Cartilage
CDMRP 11 Fellowships since 2010
BCRP & PRORP
PBS
Alkyl Side Chains Modulate pH-dependent Hemolysis
pAA
70:30 Octyl
