This presentation gives a brief introduction about the metal nanoparticle and their uptake by the cells

1. Cellular uptake of metal
nanoparticles
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For, Govt., Siddha Medical College, Chennai,
Dr. Subhathirai. S. P.
BSMS., MS (Nano)., PhD (Micro Eng.)
Assistant Professor (Sr.),
Sensor and Biomedical technology,
SENSE, VIT, Vellore, India.

2. Nanomedicine
• Nanomedicines are therapeutic particles in the size
range of 10–1000 nm.
• The drug is encapsulated into nano-capsules or
adsorbed onto nano-scaffolds.
• Nanomedicines in Siddha
• Parpam, chendooram and other incinerated metallic
preparations
• Lipid based preparations ?
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Types of nanomedicines

3. Entry routes for nanoparticles
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4. Example, oral drug reaching brain cells
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Barriers during drug deliver through oral routes
- Gastric barrier
- Low pH (1-4)
- Proteolytic enzymes
- Intestinal barrier
- Bile salts
- Thick mucus layer
- Tight epithelial junctions
- Limited permeability for
- Hydrophilic
- High molecular weight proteins
- Blood brain barrier
- Tight junction
- TEER (Transendothelial Electrical
Resistance, ~5000 W cm2)

5. Journey of drug into the body
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1. Para cellular transport-intercellular space
2. Transcellular transport-through the cell
There are two ways to enter cells

6. Paracellular transport
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Paracellular transport
- Occurs in between two cells-intercellular
space
- Small, water soluble substrates pass
through this junction
- The junction is guarded by tight junction
and gap junction proteins and ionic
gates

7. Transcellular transport
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Transcellular transport
- Occurs through the cell
- Types
- Phagocytosis
- Macropinocytosis
- Clathrin mediated endocytosis
- Caveolae-mediated endocytosis
- Clathrin and Caveolae-independent
pathway

8. Size perspective-endothelial lining
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Glycocalix
Negatively charged

9. Properties of nanoparticles
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Properties that determine the drug efficiency of
nanoparticles
- Size
- Shape
- Surface charge
- Surface functionality
- Material
Size
- Below 15 nm, removed from body
within 24 hrs, through kidney
Shape
- Rod shaped with aspect ratio of
1.5, primary accumulation in
kidney
- Rod, aspect ratio 5, retained in
spleen
Surface charge
- Neutral and zwitterion, more
circulation time

10. Fate of nanoparticle in the blood
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- Opsionation
- Corona formation
Velocity of nanoparticles in blood, 10–100 cm/s

11. Nanoparticle opsonisation
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Opsonization: is the coating of a particle with proteins that facilitate
phagocytosis of the particle by tissue macrophages and activated follicular
dendritic cells (FDCs) as well as binding by receptors on peripheral blood
cells

12. Protein corona around the nanoparticle
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13. Intercellular transport-Kinesin motor protein
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14. Uptake of gold nanoparticles by neural cells
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15. Interior of the cell
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Dispersion of nanoparticle in the macrophage

16. Nanoparticle exiting routes
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Mononuclear phagocyte system (MPS)

17. Motor protein transport
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18. Kinesin axonal transport
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19. References
• Subramaniyan Parimalam, S., Badilescu, S., Sonenberg, N., Bhat, R., & Packirisamy, M. (2019). Lab-On-A-Chip for the Development of Pro-/Anti-Angiogenic Nanomedicines to Treat
Brain Diseases. International Journal of Molecular Sciences, 20(24). https://doi.org/10.3390/ijms20246126
• Bose, T., Latawiec, D., Mondal, P. P., & Mandal, S. (2014). Overview of nano-drugs characteristics for clinical application: The journey from the entry to the exit point. In Journal of
Nanoparticle Research. https://doi.org/10.1007/s11051-014-2527-7
• Erbertseder, K., Reichold, J., Flemisch, B., Jenny, P., & Helmig, R. (2012). A coupled discrete/continuum model for describing cancer-therapeutic transport in the lung. PLoS ONE.
https://doi.org/10.1371/journal.pone.0031966
• Gatto, F., & Bardi, G. (2018). Metallic nanoparticles: General research approaches to immunological characterization. In Nanomaterials. https://doi.org/10.3390/nano8100753
• Gunawan, C., Lim, M., Marquis, C. P., & Amal, R. (2014). Nanoparticle-protein corona complexes govern the biological fates and functions of nanoparticles. Journal of Materials
Chemistry B. https://doi.org/10.1039/c3tb21526a
• Heald, R., & Walczak, C. E. (2009). Mitotic spindle assembly mechanisms. In The Kinetochore: From Molecular Discoveries to Cancer Therapy. https://doi.org/10.1007/978-0-387-69076-
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• Prasad MPharm, N., Professor, A., Neerati, P., Mohammad, R., Bangaru, R., Devde, R., & Kanwar, J. R. (2012). The effects of verapamil, curcumin, and capsaicin pretreatments on the
BBB uptake clearance of digoxin in rats. Journal of Pharmacy Research.
• Reinholz, J., Landfester, K., & Mailänder, V. (2018). The challenges of oral drug delivery via nanocarriers. In Drug Delivery. https://doi.org/10.1080/10717544.2018.1501119
• Sonia, T. A., & Sharma, C. P. (2014). Oral insulin delivery – challenges and strategies. In Oral Delivery of Insulin. https://doi.org/10.1533/9781908818683.113
• Wani, T. U., Raza, S. N., & Khan, N. A. (2019). Nanoparticle opsonization: forces involved and protection by long chain polymers. In Polymer Bulletin. https://doi.org/10.1007/s00289-
019-02924-7
• Wicki, A., Witzigmann, D., Balasubramanian, V., & Huwyler, J. (2015). Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications. In Journal of Controlled
Release. https://doi.org/10.1016/j.jconrel.2014.12.030
• Yallapu, M. M., Jaggi, M., & Chauhan, S. C. (2012). Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discovery Today. https://doi.org/10.1016/j.drudis.2011.09.009
• https://www.rch.org.au/neurology/patient_information/antiepileptic_medications/
• https://www.youtube.com/watch?v=lMliGsOqA8k
• https://www.youtube.com/watch?v=6C6547mmyfc
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