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Enabling the next generation of drug delivery through implantable medical devices

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Kevin D. Nelson, Ph.D., Founder & Chief Scientific Officer, TissueGen® Inc

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Enabling the next generation of drug delivery through implantable medical devices

  1. 1. © 2013 TissueGen 1
  2. 2. MD&M Texas Presentation© 2014 TissueGen 2 • General Advantages – Slow, sustained release – Avoid high toxic levels of therapeutic – In some applications it can be site specific – Patient compliance • Many formats – Gels – Nanoparticles – Microspheres – Fibers General Drug Delivery
  3. 3. MD&M Texas Presentation© 2014 TissueGen 3 Fiber Format for Drug Delivery • Compared to other modalities, fiber format has the following advantages: – Mechanically strong – Slower release than spheres of same diameter – Stays in place – Readily explanted – Highly uniform diameter and drug concentration – Readily mass produced – Coatings and complex geometries
  4. 4. MD&M Texas Presentation© 2014 TissueGen 4 Fiber Fabrication Techniques • Melt extrusion – High temperature melt – High shear stress – Small set of pharmaceuticals can survive • Electrospinning – Mats/filters/sheets/tubes but not individual fiber – Wide variation in diameter – Wide range of drugs • Wet spinning
  5. 5. MD&M Texas Presentation© 2014 TissueGen 5 • Room temperature • Low Shear Stress • Virtually any pharmaceutical or biologically derived therapeutic • Solvent • Coagulating bath • Technique Paper for Wet-Spinning Poly(L-lactic acid) and Poly(DL-lactide-co-glycolide) monofilament fibers. Tissue Engineering 9(6):1323- 30 (2003) Wet Spinning (Extrusion)
  6. 6. MD&M Texas Presentation© 2014 TissueGen 6 Solvent Systems • Potentially harsh organic solvents • High potential to damage drug • Must remove from end-product • Costly to purchase and dispose appropriately
  7. 7. MD&M Texas Presentation© 2014 TissueGen 7 The Solution is the Solution • Drug must be protected – Isolated from surrounding solvent system – Excipients may encase the drug – Create a “bubble of happiness” for drug within the sea of potentially harsh solvents • Drugs we have been successful with include pharmaceuticals, proteins, even viruses
  8. 8. MD&M Texas Presentation© 2014 TissueGen 8 • Wide range of hydrophobic to hydrophilic • Small to large molecular weight – Antibiotics – Antimicrobials – Cancer remediation Wide Range of Pharmaceuticals (Note bubble size proportional to amount loaded - mean 1.36ug/mm^2) 0 200 400 600 800 1000 1200 1400 1600 -3 -2 -1 0 1 2 3 4 5 6 logP value MolecularWeight
  9. 9. MD&M Texas Presentation© 2014 TissueGen 9 • Proteins • VEGF • NGF • Fab fragment of IgG • BSA • Lysozyme • Matrigel • Collagen • DNA • -galactosidase adenovirus Drugs (Biological Therapeutic Agents)
  10. 10. MD&M Texas Presentation© 2014 TissueGen 10 Available Polymers • Polymer restrictions: – Solvents must exist – Non-solvents must exist – At least one combination of solvent and non-solvent must be miscible • Synthetic polymers that we have been able to work with • Poly(L-lactic acid) (“PLLA”) • Poly(D,L-lactic acid) (“PDLLA”) • Poly(lactic acid-co-glycolic acid) (“PLGA”) • Poly(p-dioxanone) (“PDO" also referred to as “PDS”) • Blends with poly(-caprolactone) (“PCL”) • Poly(glycolic acid) (“PGA”) under development • Biopolymers: • Chitosan  Silk • Chitosan/alginate blends  Silk blended with synthetic polymers
  11. 11. MD&M Texas Presentation© 2014 TissueGen 11 Currently Available Clinical Applications • Textiles – Sutures – Hernia mesh – Pouch or sling – Tendon/Ligament • Regenerative medicine applications – Nerve repair conduit • Drug Depot applications – Retinal delivery – Growth factor delivery – Solid tumor remediation
  12. 12. MD&M Texas Presentation© 2014 TissueGen 12 7 weeks 6 months IntracellularRetinalSorbitolLevel(nmol/g) 0 200 400 600 800 1000 1200 Control gp non treated treated • TissueGen demonstrated potential diabetic retinopathy treatment. • Aldose Reductase Inhibitor blocks conversion of glucose to sorbitol, a potential cause of blindness in diabetic patients. • Drug-loaded fibers implanted into one eye of diabetic rats compared with untreated eye in the same animal and age-matched, normal healthy animals. • Indicators of diabetic state reduced 5-fold. • Treatment sustained for at least 6 months with one dose. Aldose Reductase Inhibitor In Vivo Animal Test Results Healthy Treated Untreated
  13. 13. MD&M Texas Presentation© 2014 TissueGen 13 • Nerve regeneration – Long peripheral gaps – Spinal cord repair • Small diameter vascular grafts • Soft tissue repair • In-place differentiation of progenitor cells Potential 2nd Generation Applications
  14. 14. MD&M Texas Presentation© 2014 TissueGen 14 • Embryonic development tissue formation is guided by protein embedded into and released from the extracellular matrix • Advanced wound care in adults can happen in the same way by fibers that release those same protein • Protein loaded fibers direct tissue growth/regeneration Science Behind 2nd Generation
  15. 15. MD&M Texas Presentation© 2014 TissueGen 15 • Precursor myoblast cells were seeded onto fibers which were then differentiated into myocytes • Chemical signals for differentiating pluripotent cells can be loaded and released • Potential for location specific cell differentiation Cell Differentiation on Fibers
  16. 16. MD&M Texas Presentation© 2014 TissueGen 16 • Fibers with pharmaceuticals • Next generation of medical textiles – Pharmaceutical support at the site of surgery – Reduced healing time – Patient compliance • Fibers with biological agents – Proteins • Growth factors • Cell migration • Cell differentiation – DNA • Cell function at specific location • Tissue regeneration advanced healing Conclusions
  17. 17. MD&M Texas Presentation© 2014 TissueGen 17 Questions??

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