Nanomaterial Drug Delivery

1. Nanomaterial Drug Delivery http://research.mdhs.unimelb.edu.au/event/nano-medicine-bio21-cluster-symposium https://encrypted-tbn1.gstatic.com/images?q=tbn:ANd9GcSh0iVqg8Z7WUm1a_XO7uTQQpHl67Lz1El1kl2YHlNy4qkCEz2KBQ Group 5: Daniel Ehlers Daniel Barnes Ann-Marie Scarborough Nguyen Lam Featuring: Nanomaterials For Drug Delivery

2. Interactive Presentation • To view an interactive version of this presentation, visit the link below (recommended): • http://prezi.com/qa0bx-dztksu/untitled-prezi/

3. Nanomaterials are the future of drug delivery http://mayoresearch.mayo.edu/dev_lab/images/single_drug.gif http://nextbigfuture.com/2011/01/nanorattle-drug-delivery.html Drugs are able to reach their site of action more effectively

4. Bodily system barriers are able to be broken with nanocarriers http://onlinelibrary.wiley.com/store/10.1002/mabi.201100419/asset/image_m/mcontent.jpg?v=1&s=2899b61a4ddaff99e1b18b7a79ea871a7f4eaabc Advanced materials can target various cells, such as cancer cells. http://ultraphyte.com/2012/02/26/nanorobot-detects-cancer/

5. Drugs with different molecular shapes and chemical properties can be synthesized Different properties results in greater possibilities http://www.azonano.com/images/news/NewsImage_23414.jpg http://sina.sharif.edu/~adeli/?view=Synthesis_of_Hybrid_Nano_Structures&id=15

6. Background Information • All drugs face several transport barriers • Plasma membrane • The acidic environment of endolysosomes • Nuclear membrane • Multiple drug resistance mechanism from their site of introduction to their molecular site of action.

7. Background Information https://dl-web.dropbox.com/Articles/1-s2.0-S0169409X1200021X-main.pdf?w=AACRdlAYxdLRb6iZvjRVrMMwvLN-ChawIar3xGlbaupaGw

8. Advantages High-resolution image of detonation nanodiamonds 1. Very small size 2.High surface-to-volume ratio 3. One or more therapeutic drugs can be attached to http://nanoall.blogspot.com/2012/01/synthesis-of-metallic-nanoparticles.html

9. Advantages 4.Attach to specific target cells and organs with selected binding agents 5.Helps to avoid the fluctuations of drug (by using time-release) https://dl-web.dropbox.com/Articles/1-s2.0-S0169409X1200021X-main.pdf?w=AACRdlAYxdLRb6iZvjRVrMMwvLN-ChawIar3xGlbaupaGw

10. Polymers and Cancer Cells • Other polymers allow for easy binding to tumor sites • At the correct pH and/or [Cl-] of a tumor site, the drug can be released • Certain polymers allow for delivery past protective DNA barriers in a tumor cell http://static5.businessinsider.com/image/500ff7b2eab8ea2b60000001-590/this-mix-of-polymers-and-cancer-medicines-would-then-attach-to-nanoparticles.jpg

11. Cylindrical Miccles • Initially block polymers • Hydrophillic end – causes them to form miccle shape with water • Hydrophobic end – Keeps them from being easily bound/absorbed to other things • Benefits: • Prolonged circulation • Reduction of off-target toxicity (less side effects) • Can be formed using existing drugs http://news.rice.edu/images/media/2006RiceNews/1130_gold_nano.jpg

12. PEGylation of Drugs • Adding PEG (Polyethylene glycol) polymer to existing drug molecular structure • Benefits: • Increases drug half life • Increases drug solubility at site of action • Increases drug stability • Slows down drug metabolism through kidneys, etc. http://www.peg-drug.com/images/peg-top_photo2.jpg

13. Ideal siRNA Cancer Drug • siRNA – Small Interfering RNA can be inserted into a tumor cell to cause it to malfunction • Problem: Needs to be delivered to tumor site and not to healthy cells • In figure, nanomaterial (green) is attached to siRNA drug (purple ring) http://www.sciencemag.org/content/337/6092/303/F1.large.jpg

14. Ideal siRNA Cancer Drug • Nanomaterial is PEGylated: • Increases drug half life • Increases drug solubility at site of action • Decreases interaction outside target side (and therefore side effects) • Increases drug stability • Slows down drug metabolism through kidneys, etc. http://www.sciencemag.org/content/337/6092/303/F1.large.jpg

15. Ideal siRNA Cancer Drug • Nanomaterial searches for biological signals of a cancer cell • Certain peptides have this ability • Nanomaterial is engineered to bind to the unique receptors on the cancer cell http://www.alternative-cancer.net/images/cell_attack.jpg

16. Ideal siRNA Cancer Drug • Another problem: Overcome defenses in cytoplasm of cancer cell • Nanomaterial overcomes defenses and rapidly delivers siRNA drug into cell • siRNA modifies the cancer cell DNA and causes it to die http://www.sciencemag.org/content/337/6092/303/F1.large.jpg

17. Specific Cancer Drug Design: Carbon Nanotubes • Antibodies are designed that will fight cancer cells • Carbon Nanotube carriers have molecular strands that contain the antibodies and a link system to cancer cells • Recognize cancer cells by pH, biological markers http://www.ncbi.nlm.nih.gov/pubmed/23143677

18. Specific Cancer Drug Design: Carbon Nanotubes • Carbon Nanotubes can be PEGedand attached with antibodies to bring it specifically to a cancer cell • The drugs inside the nanotube can be released in the presence RF frequencies • Metal nanotubes also heat in presence of RF waves, and “burn up” cancer cells http://www.ncbi.nlm.nih.gov/pubmed/23143677

19. Specific Cancer Drug Design: Nanodiamonds • Drug can be placed in nanodiamonds • Nanodiamonds contain receptors that allow them only to bind and react with tumor cells • Nanodiamonds release drug into tumor cell and result in highly effective treatment http://www.sciencedaily.com/releases/2013/04/130415172308.htm

20. Assessment of Work • The use of Nano-Diamonds and their effects on the PH increase solubility in the solution for several types of deliveries by making the pH closer to that of the natural body levels • Table 1 • Plotted n value of the release of RB from carbon nanomaterials at pH 7.4 and pH 4.5. • n value at pH 7.4 n value at pH 4.5 Drug release mode • CB–RB 0.39 0.32 Fickian diffusion • CNT–RB 0.42 0.64 Fickian diffusion at pH 7.4, • anomalous transport at pH 4.5 • f-CNT–RB 0.5 0.64 Anomalous transport • GO–RB 1 0.63 Case II transport at pH7.4, • anomalous transport at pH 4.5 • Zhang and Olin Pg. 1251

21. Assessment of Work • In addition, they allow for a controlled time release of the drug for consistant delivery • Zhang and Olin pgl. 1250 Time (min)

22. Assessment of Work • Allows better ability to Penetrate the Plasma wall of the cells • Can release on correct rNA code recognition for needed antigen.

23. Conclusions • The use of Nano-Diamonds allows the Pharmicutical Industry to be much more presice in drug delivery due to • pH Control • Time Release Control • rNA Release Control

24. Conclusion • It also allows a larger range of effective drugs to be administered from • Size Control • pH Control

25. Further Research Suggested • Hazards/toxicity of particles • Cancer research http://research.mdhs.unimelb.edu.au/event/nano-medicine-bio21-cluster-symposium http://www.healingrosacea.com/images/nanomaterial-in-cancer-therapy1.jpeg http://www.dddmag.com/sites/dddmag.com/files/legacyimages/Articles/2009_09/pnp.jpg

26. References • Nanomaterials for Drug Delivery. Jeffrey A. Hubbell and AshutoshChilkoti. Science 20 July 2012: 337 (6092), 303-305. [DOI:10.1126/science.1219657] • Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems. Badea, Ildiko and Kaur, Randeep. International Journal of Nanomedice. 8. Jan 2013. Web. 2 April 2013 • Computational design of a CNT carrier for a high affinity bispecificanti-HER2 antibody based on trastuzumaband pertuzumabFabs. Salazar-Salinas Karim, Kubli-Garfias, Carlos, and Seminario, Jorge M. Springer-Verlag.