1. Nanomaterial Drug Delivery Group 5: Daniel Ehlers Daniel Barnes Ann-Marie Scarborough Nguyen Lam Featuring: Nanomaterials For Drug Delivery https://encrypted- tbn1.gstatic.com/images?q=tbn:ANd9Gc Sh0iVqg8Z7WUm1a_XO7uTQQpHl67Lz1El1k l2YHlNy4qkCEz2KBQ http://research.mdhs.unimelb.e du.au/event/nano-medicine- bio21-cluster-symposium

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

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

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

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

6. Background Information All drugs face several transport barriers o Plasma membrane o The acidic environment of endolysosomes o Nuclear membrane o 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 1. Very small size 2.High surface-to-volume ratio High-resolution image of detonation nanodiamonds http://nanoall.blogspot.com/2012/01/synthesis-of-metallic- nanoparticles.html 3. One or more therapeutic drugs can be attached to

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: o Prolonged circulation o Reduction of off-target toxicity (less side effects) o 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: o Increases drug half life o Increases drug solubility at site of action o Increases drug stability o 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: o Increases drug half life o Increases drug solubility at site of action o Decreases interaction outside target side (and therefore side effects) o Increases drug stability o 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 o 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 PEGed and 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 o pH Control o Time Release Control o rNA Release Control

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

25. Further Research Suggested Hazards/toxicity of particles Cancer research http://research.mdhs.unimelb.e du.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.j pg

26. References 1. Nanomaterials for Drug Delivery. Jeffrey A. Hubbell and Ashutosh Chilkoti. Science 20 July 2012: 337 (6092), 303-305. [DOI:10.1126/science.1219657] 2. 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 3. Computational design of a CNT carrier for a high affinity bispecific anti-HER2 antibody based on trastuzumab and pertuzumab Fabs. Salazar-Salinas Karim, Kubli-Garfias, Carlos, and Seminario, Jorge M. Springer-Verlag.