Hadorn Biostec 2010

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Single liposomes and vesicles are successfully utilized as delivery vehicles of pharmaceuticals. However limitations of these unilamellar, single compartments led to the development of encapsulated multicompartment systems that establishes the prospect of multicomponent or multifunctional drug delivery systems. So far compartmentalization is restricted to binary systems. To realize a personalized drug delivery, a programmable linkage of n-entities of different content will be needed. Here we present both a programmable DNA-mediated linkage of three distinct vesicle populations and a novel encapsulation protocol. We discuss how the techniques established in this study might be used in personalized healthcare based on custom tailored encapsulated multicompartment vesicular drug delivery systems.

TOWARDS PERSONALIZED DRUG DELIVERY – Preparation of an Encapsulated Multicompartment System. Third International Conference on Biomedical Electronics and Devices (BIODEVICES 2010), Valencia, Spain (20-23 January, 2010), 30 minutes oral presentation.

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Hadorn Biostec 2010

  1. 1. TOWARDS PERSONALIZED DRUG DELIVERY<br />–<br />Preparation of an Encapsulated Multicompartment System<br />
  2. 2. Prodrugs =overcoming barriers in clinical drug application<br />«<br />Many therapeutic drugs have undesirable properties that may become […] barriers in clinical drug application. […]<br />Prodrugs [are] pharmacologically inert chemical derivatives that can be converted [e.g. enzymatically] in vivo to the active drug molecules to exert a therapeutic effect. Ideally, the prodrug should be converted to the original drug as soon as the goal is achieved […].<br />Han HK, 2000. AAPS Pharmsci2(1):article 6.<br />»<br />
  3. 3. Prodrugs =demanding in application<br />
  4. 4. Single Liposomes =30 years ofevolution of drug carriers<br />immuno-<br />liposome<br />long-circulating<br />liposome<br />long-circulating<br />immunoliposome<br />new generation<br />liposome<br />liposome<br />Torchilin VP, 2005. Nature Reviews Drug Discovery 4(2):145-160.<br />
  5. 5. Scenario =<br />personalized drug delivery<br />modified: Davis ME, Chen Z, et al., 2008. Nature Reviews Drug Discovery7(9):771-782.<br />
  6. 6. Dividing the Volumes and Membranes =<br />generating new perspectives but also new challenges<br />«<br />»<br />There are many potential benefits of [multicompartment aggregates of liposomes] over typical [single liposomes] used in applications.<br />Walker SA, Kennedy MT, and Zasadzinski JA, 1997. Nature387(6628):61-64.<br />long-circulating<br />immunoliposome<br />CHALLENGES:<br /><ul><li> Defined Architecture
  7. 7. Defined Communication
  8. 8. Defined Encapsulation</li></ul>prodrug carrying<br />liposome<br />enzymosome<br />
  9. 9. Dividing the Volumes and Membranes =<br />generating new perspectives but also new challenges<br />«<br />»<br />There are many potential benefits of [multicompartment aggregates of liposomes] over typical [single liposomes] used in applications.<br />Walker SA, Kennedy MT, and Zasadzinski JA, 1997. Nature387(6628):61-64.<br />CHALLENGES:<br /><ul><li> Defined Architecture
  10. 10. Defined Communication
  11. 11. Defined Encapsulation</li></ul>long-circulating<br />immunoliposome<br />prodrug carrying<br />liposome<br />enzymosome<br />
  12. 12. 1st Challenge =<br />defined architecture of multicompartment aggregates<br /><ul><li> not self-terminating
  13. 13. no multitude of containers</li></ul>Chiruvolu S, Walker S, Israelachvili J, Schmitt FJ, Leckband D, and Zasadzinski JA, 1994. Science 264(5166):1753-1756.<br />
  14. 14. Challenge 1.1: multitude of distinct containers<br />DNA = putting the ‘multi’ in multicompartment aggregates<br />Beales PA and Vanderlick TK, 2007. J. Phys. Chem. A 111(49):12372-12380.<br />α<br />α<br />α‘<br />α‘<br />modified: Benkoski JJ, Höök F, 2005. J. Phys. Chem. B 109:9773-9779.<br /><ul><li> not self-terminating</li></li></ul><li>Challenge 1.2: self-termination<br />Adhesion Plaques = creating the ‘HALT’<br />Hadorn M, Burla B, and Eggenberger Hotz P, 2009. 4th Australian Conf. on Artificial Life.<br />
  15. 15. Challenge 1.2: self-termination<br />Adhesion Plaques = creating the ‘HALT’<br />
  16. 16. Challenge 1.2: self-termination<br />Adhesion Plaques = creating the ‘HALT’<br />
  17. 17. Challenge 1.2: self-termination<br />Adhesion Plaques = creating the ‘HALT’<br />
  18. 18. Challenge 1.2: self-termination<br />Adhesion Plaques = creating the ‘HALT’<br />
  19. 19. Challenge 1.2: self-termination<br />Adhesion Plaques = creating the ‘HALT’<br />Hadorn M, Burla B, and Eggenberger Hotz P, 2009. 4th Australian Conf. on Artificial Life.<br />
  20. 20. 1st Challenge: defined architecture<br />DNA-mediated self-assembled and self-terminated aggregates<br />Hadorn M, Eggenberger Hotz P (2010). DNA-Mediated Self-Assembly of Artificial Vesicles. Plos One 5(3):e9886.<br />
  21. 21. Dividing the Volumes and Membranes =<br />generating new perspectives but also new challenges<br />«<br />»<br />There are many potential benefits of [multicompartment aggregates of liposomes] over typical [single liposomes] used in applications.<br />Walker SA, Kennedy MT, and Zasadzinski JA, 1997. Nature387(6628):61-64.<br />CHALLENGES:<br /><ul><li> Defined Architecture
  22. 22. Defined Communication
  23. 23. Defined Encapsulation</li></ul>long-circulating<br />immunoliposome<br />prodrug carrying<br />liposome<br />enzymosome<br />
  24. 24. 2nd Challenge =<br />defined communication<br />www.orwarlab.org<br />Stengel G, Zahn R, and Hook F, 2007. Journal of the American Chemical Society129(31):9584-9585.<br />Bolinger PY, Stamou D, et al., 2008. Angewandte Chemie-International Edition47(30):5544-5549.<br />
  25. 25. Dividing the Volumes and Membranes =<br />generating new perspectives but also new challenges<br />«<br />»<br />There are many potential benefits of [multicompartment aggregates of liposomes] over typical [single liposomes] used in applications.<br />Walker SA, Kennedy MT, and Zasadzinski JA, 1997. Nature387(6628):61-64.<br />CHALLENGES:<br /><ul><li> Defined Architecture
  26. 26. Defined Communication
  27. 27. Defined Encapsulation</li></ul>long-circulating<br />immunoliposome<br />prodrug carrying<br />liposome<br />enzymosome<br />
  28. 28. 3rd Challenge =<br />defined encapsulation<br />Bolinger PY, Stamou D, et al., 2008. Angewandte Chemie-International Edition47(30):5544-5549.<br />Walker SA, Kennedy MT, and Zasadzinski JA,1997. Nature387(6628):61-64.<br />
  29. 29. 3rd Challenge =<br />defined encapsulation<br />Hadorn M and Eggenberger Hotz P, 2010. BIOSTEC, Valencia, Spain, Jan 20-23, 2010.<br />
  30. 30. Peter EggenbergerHotz<br />Associated Professor<br />Mærsk Mc-Kinney Møller Institute<br />University of Southern Denmark<br />Enrico Martinoia<br />Professor<br />Institute of Plant Biology<br />University of Zurich<br />Rolf Pfeifer<br />Professor<br />Artificial Intelligence Laboratory<br />University of Zurich<br />Acknowledgments<br />Bo Burla<br />PhD Student<br />Institute of Plant Biology<br />University of Zurich<br />Eva Bönzli<br />PhD Student<br />Faculty of Veterinary Medicine<br />University of Zurich<br />EU_ProjectPACE<br />EU-IST-FP6-FET-002035<br />SNSF-Project EES<br />200020-118127<br />

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