1 / 27

The Putnam Lab

Controlled Release. siRNA. Vaccines. Bioadhesives Biolubricants. Adjuvants. plasmid DNA. The Putnam Lab. Project Distributions. Outer Membrane Vesicle Engineering. Delivery of Nucleic Acid-Based Therapeutics. Biomaterial Design and Synthesis. Multifactorial biomaterial

olive
Download Presentation

The Putnam Lab

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Controlled Release siRNA Vaccines Bioadhesives Biolubricants Adjuvants plasmid DNA The Putnam Lab Project Distributions Outer Membrane Vesicle Engineering Delivery of Nucleic Acid-Based Therapeutics Biomaterial Design and Synthesis

  2. Multifactorial biomaterial design and synthesis Quantify efficacy of each unique structure Biophysical and subcellular characteristics Approachpolymeric libraries with serial changes in composition Goal: Quantitative, mechanistic understanding of transfection

  3. Controlled Release siRNA Vaccines Bioadhesives Biolubricants Adjuvants plasmid DNA The Putnam Lab Project Distributions Outer Membrane Vesicle Engineering Delivery of Nucleic Acid-Based Therapeutics Biomaterial Design and Synthesis

  4. Motivationthe human body is a monomer factory • New polymeric biomaterials from metabolic synthons • Investigate metabolic pathways • Identify interesting monomers • Akin to PLGA polyesters • Rational/targeted selection • Engineered polymer properties • Synthetically challenging http://www.science.gmu.edu/~gsudama/csi803s97/met2.gif

  5. Dihydroxyacetone (DHA) Glucose • Glucolytic metabolite DHA Pyruvic acid Scheme 1: Glycolysis pathway

  6. Dihydroxyacetone (DHA) Glucose • Glucolytic metabolite • FDA approved for use in oral and topical administration (the active ingredient in sunless tanning lotions). DHA Pyruvic acid Scheme 1: Glycolysis pathway http://www.premiersalonsystems.com/ http://www.procyte.com/products/brand/asp/titanfoaming.shtml

  7. a Water insoluble block Water soluble block b c d PEG-pDHASynthesis, characterization and application Postoperative adhesions Seroma closure Fistula blockade Chemo-emboli Zawaneh, P.; Doody, A.; Zelikin, A.; Putnam, D. Biomacromolecules (2006)

  8. HYPOTHESIS Release slower with increasing lipid chain length DHA-based lipidsSynthesis

  9. C10 C8 C12 C14 C16 DHA-based lipidsRelease kinetics

  10. Controlled Release siRNA Vaccines Bioadhesives Biolubricants Adjuvants plasmid DNA “Career path and research which have led you” Project Distributions Outer Membrane Vesicle Engineering Delivery of Nucleic Acid-Based Therapeutics Biomaterial Design and Synthesis

  11. http://www.molbiol.umu.se/forskning/wai/ Outer membrane vesicles (OMVs)natural vesicles for transfer of proteins and DNA GOAL Engineered vesicles to correctly fold and stabilize proteins Optimize antigen presentation to APCs APPLICATIONS Expression/stabilization/delivery of conformational antigens Novel adjuvants to enhance existing or poorly effective vaccines Periplasmic proteins are entrapped within the OMV lumen LPS OM Per PG IM Cyt Kuehn and Kesty (2005) Genes Dev 19: 2645-55

  12. Section 2 • Joint project with Neurological Surgery • ChemoCoils and Brain PhantomCreation and Validation of a Novel Drug Delivery Technique • Michael Shuler, Susan Pannullo, David Putnam, Jian Tan

  13. ChemoCoils and Brain PhantomCreation and Validation of a Novel Drug Delivery Technique Cornell Cross-Campus Neurological Surgery/Biomedical Engineering Project Michael Shuler, Susan Pannullo, David Putnam, Jian Tan July 2007

  14. Reviewing the ProblemMalignant Gliomas • Highly aggressive brain cancers • Recur locally  need good local control techniques • Only 1 validated/FDA approved device: chemotherapy wafers • Minimal survival benefit • Poor conformality to resection cavity • Minimal brain penetration • Submaximal dose • Only one drug (BCNU) delivered • Drug delivery poorly understood

  15. Chemotherapy Coils and Brain Phantom: The Project Year 1 • Development of an in vitro “Brain Phantom” based upon Magnetic Resonance Imaging of human brain and brain tumor • Development of polymer coils with appropriate mechanical, chemical, and drug release properties. • Test, using dyes and IMAGING, the distribution, depth of penetration, and duration of chemical dyes from different polymer formulations Year 2 • Refinement of delivery system/drug mixtures • Animal trials • Clinical trials Hypothesis Maintaining contact with cavity wall will improve treatment outcomes

  16. Controlled Release Polymer • Incorporate both p(CPP:SA) (poly (carboxyphenoxypropane-sebacic acid) and polyester of ε-caprolactone • Diameter and porosity are controlled by electrospinning • Wafer: 14mm in diameter and 1mm thick • Mesh: interwoven fibers (<1μm); multiple reporter “drugs” • Coil: order of 0.1mm size, mix of different coils

  17. Pressure Model • Brain experiences around 10mmHg of pressure in brain cavity. • For our first experiments we will use a simple water tank to create the pressure. 14cm

  18. Alternate Pressure Model Syringe to alter pressure Agarose Brain Pressure Probe Silicone Encapsulation

  19. Mathematical Model • Simulate the transport of drugs from various polymer constructs to the brain • Assumption: transport of drug occurs by diffusion and convection (due to edema) with elimination (e.g. internationalization) • Goal: to predict drug concentration and deduce drug penetration in the artificial tissue, then compare with our brain phantom model

  20. Section 3 • Bill Olbricht • Microcatheters for drug delivery to the brain

  21. Microcatheters for Convection-Enhanced Delivery Diffusion only gets you so far. Convection can get you further.

  22. 5 mm Remodeling ECM to enhance nanoparticle delivery Channel 1: Deliver enzymes that degrade ECM components (hyaluronan and chondroitan sulfate proteoglycans) to increase permeability OR hyperosmolar solutions that swell interstitium to increase permeability Channel 2: Deliver drug-laden nanoparticles to reduce drug elimination during transport in tissue and extend release time

  23. Flexible microfluidic catheters

  24. Section 4 • C. C. Chu • Materials for drug delivery

  25. C. C. Chu • Biodegradable hydrogels as cytokine (IL-12) carriers for immunotherapy of cancer. • Estone carrier from polysaccharides. • Biodegradable carriers of nitric oxide derivatives for nitric oxide biofunctionality. • Biodegradable hydrogels and microspheres as anticancer drug (e.g., Doxorubicin, Paclitaxel) carriers. • Biodegradable hydrogels as gene carriers

  26. 2. Biodegradable carriers for nitric oxide derivatives (NOD): a. NOD conjugated with biodegradable biomaterials. b. NOD Impregnated within biodegradable microspheres or nanofibers. 10 conjugated Phenylalanine-based poly(ester amide) microspheres w/ 10 mg NO/g PEA - 2.5 2 6 Nitroxyl radical release (%) 1.5 1 2 0.5 0 0d 2d 4d 9d PGA, PLA, PEA • Cytokine carriers for immunotherapy: • Interleukin 12 impregnated within Arginine-based biodegradable hydrogels. • Burst release followed by sustained release over 3 mo. wo/ bioactivity loss. • 4 factors control IL-12 release – charge, hydrophilicity, gel crosslinking density, biomaterial biodegradation. Dry water

  27. Doxorubicin release 3. Estrone carrier from polysaccharides: a. Starch-estrone conjugate. b. Dextran-estrone conjugate. pH 8 pH 7.4 O Polysaccharide – O – C – CH2 - Estrone 4.Biodegradable hydrogels and microspheres as anticancer drug carriers: a.from poly(ester amide) gel and microspheres b. from intelligent polysaccharide-synthetic hydrogels Poly(ester amide) gel Intelligent Dextran-synthetic hydrogels

More Related