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

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Nanomaterials are the future of drug delivery Drugs are able to reach their site of action more effectively

ontent.jpg?v=1&s=2899b61a4ddaff99e1b18b7a79ea871a7f4eaabc Bodily system barriers are able to be broken with nanocarriers Advanced materials can target various cells, such as cancer cells.

Drugs with different molecular shapes and chemical properties can be synthesized Different properties results in greater possibilities

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.

Background Information

Advantages 1. Very small size 2.High surface-to-volume ratio High-resolution image of detonation nanodiamonds nanoparticles.html 3. One or more therapeutic drugs can be attached to

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) main.pdf?w=AACRdlAYxdLRb6iZvjRVrMMwvLN- ChawIar3xGlbaupaGw

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 590/this-mix-of-polymers-and-cancer-medicines-would-then-attach-to- nanoparticles.jpg

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

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.

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)

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.

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

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

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

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

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

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 Fickian diffusion CNT–RB Fickian diffusion at pH 7.4, anomalous transport at pH 4.5 f-CNT–RB Anomalous transport GO–RB Case II transport at pH7.4, anomalous transport at pH 4.5 Zhang and Olin Pg. 1251

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

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

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

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

Further Research Suggested Hazards/toxicity of particles Cancer research du.au/event/nano-medicine- bio21-cluster-symposium pg

References 1. Nanomaterials for Drug Delivery. Jeffrey A. Hubbell and Ashutosh Chilkoti. Science 20 July 2012: 337 (6092), [DOI: /science ] 2. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems. Badea, Ildiko and Kaur, Randeep. International Journal of Nanomedice. 8. Jan Web. 2 April 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.