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Associate Professor, Biomedical Engineering · PDF fileAssociate Professor, Biomedical Engineering. Vanderbilt University, Nashville, Tennessee, USA. Breast Cancer Therapies. ... Ex

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  • Advanced Therapeutics LaboratoryCraig Duvall, Ph.D.

    Associate Professor, Biomedical EngineeringVanderbilt University, Nashville, Tennessee, USA

    Breast Cancer TherapiesDOD BCRP & NIH NCI R01

    Vascular Graft TherapiesNIH NHLBI R01

    Improved siRNA Polyplex Chemistries for In Vivo Gene Knockdown

    Scaffolds and Cell DeliveryNSF CAREER & NIH NIBIB R01

    siRNA Lipid Conjugates for Carrier-Free Gene Silencing

    Overview

    RAFT Polymerization Allows Rational Design of Diverse Polymers

    Scaffoldsfor large tissue defects

    Microspheresfor local, controlled

    drug release

    Nanoparticlesfor intracellular

    biologic drug delivery

    Polymeric Materials to TackleMulti-Scalar Drug Delivery Challenges

    ROS-Responsive Materials Match Degradation to Tissue Infiltration

    Polymer-enhanced Peptide Drug Delivery Prevents Vascular Graft Failure

    In Vivo Luciferase Knockdown

    Days

    CellularInternalization

    pH-triggered Endosomal Escape

    Intracellular Release

    Clinical Application

    Nanoparticle Formulation Intracellular DeliverypH-responsive

    Polymer

    TherapeuticPeptide

    ElectrostaticComplexation

    Local Delivery of siRNA Modulates Tissue Healing The Advanced Therapeutics Laboratory focuses on

    the design and applications of novel polymer-based materials for drug delivery

    Improved Graft Patency

    Vein graftharvest

    Ex vivo treatment

    SurgicalImplantation

    Galectin-8 recruitment shows real time endosomal escape

    Pept

    ide

    Nan

    opar

    ticle

    0 min 60 min

    Endosome Escape Screening

    ROS-Shielding Hydrogels for Therapeutic Cell Delivery

    Local Degradation Environmental Activation

    Thermal GelationpH Responsive Hydrophobicity

    Allows Many Polymer Backbone Architectures

    Defined End Groups for Pre- or Post-Polymerization Conjugates

    RAFT Chain Transfer Reagent Polymer

    Initiator

    Monomer (M)

    = R Group = Z Group

    Smart polymers can respond to changes in temperature, pH, reactive oxygen species, enzymes, and more!

    PDN Hydrogels Solidify Upon Heating

    CDMRPBCRP & PRORP

    11 Fellowshipssince 2010

    Osteoarthritis TherapiesDOD PRORP

    Intra-articular Drug Delivery Treats Osteoarthritis

    Cartilage Damage (CII680)

    (x107)

    5

    8

    PPS-

    MS

    Salin

    e

    PPSPoly(Propylenesulfide)

    Emulsion

    Antioxidant Microspheres

    Antibody Conjugated Nanoparticles Target Damaged Cartilage

    Antioxidant Microspheres Provide Local Sustained Drug Delivery

    No

    rma

    lize

    dM

    MP

    -13

    E

    xp

    res

    sio

    n

    No

    Tx

    mA

    bC

    II N

    P

    Ba

    re N

    P

    No

    Tx0 .0

    0 .5

    1 .0

    1 .5

    + O A

    * *

    *

    Intracellular Deliveryof siRNA

    Targeted Accumulation in Joint Space

    YFP

    Gal8

    Glycan

    Gal8

    YFP

    Endosomal Membrane Intact; Gal8 binding blocked

    EndosomalMembrane Disrupted; Gal8 binds and induces punctate fluorescence

    Gal8-YFPReporter Cell

    Endosome

    Endosome

    Gal8-YFPReporter Cell

    Alkyl Side Chains Modulate pH-dependent Hemolysis

    Graft Copolymer Library for Structure-Function Characterization

    PBS pAA 70:30 Octyl

    Slide Number 1