Using Coated Nanoparticles for Effective Drug Delivery
Why drug delivery research?
Professor Luke Theogarajan conducts research in site-specific drug delivery, which was a spin-off of his research on neural prosthetics. His PhD work dealt with retinal implants, which involved creating membranes that behaved like cells and building robust membranes. These membranes can also form into vesicles, or pouches, which can be used to encapsulate drugs for treatment; Professor Theogarajan's work on polymer membranes was easily translated to drug delivery research.
Professor Theogarajan's motivation to conduct research with biomedical applications is to improve the quality of life for people with conditions or diseases. His motivation for drug delivery research is highlighted in the video below.
Professor Theogarajan's motivation to conduct research with biomedical applications is to improve the quality of life for people with conditions or diseases. His motivation for drug delivery research is highlighted in the video below.
What is the problem that is addressed by site-specific drug delivery?
Chemotherapy is a common treatment for cancer patients; it targets and kills cell that reproduce quickly. However, the treatment cannot differentiate between cancer cells and healthy cells; this is the cause of the many effects associated with cancer treatment such as hair loss, nausea, and fatigue. These side effects significantly reduce the life expectancy of the patient due to the physical and psychological changes. Site-specific drug delivery aims to improve the effectiveness of cancer treatment by targeting cancer cells only and preventing the deaths of healthy cells during treatment.
How does site-specific drug delivery work and what are the current problems of this technology?
Drugs are delivered to specific locations and specific organs in the body where cancer cells or tumors are present. Drugs are encapsulated in polymer vesicles, also called nanoparticles, which are injected directly into the bloodstream of the patient. Once the drugs reach the targeted area inside the body, the drugs are released and kill the cancer cells present.
Current nanoparticles are coated with a material called PEG; these nanoparticles are very effective for the first injection or the first treatment. However, the nanoparticles are foreign objects. The body's immune systems build up a defense to these nanoparticles; therefore, subsequent treatments with the PEG coated nanoparticles are made useless.
Professor Theogarajan's research in drug delivery is to find a new class of membrane materials that will serve as alternative to PEG, which would provide consistent effective treatments that would not be resisted by the immune system.
Current nanoparticles are coated with a material called PEG; these nanoparticles are very effective for the first injection or the first treatment. However, the nanoparticles are foreign objects. The body's immune systems build up a defense to these nanoparticles; therefore, subsequent treatments with the PEG coated nanoparticles are made useless.
Professor Theogarajan's research in drug delivery is to find a new class of membrane materials that will serve as alternative to PEG, which would provide consistent effective treatments that would not be resisted by the immune system.
How are the nanoparticles made and what are they made of?
The nanoparticles are made in a microfluidic channel with three inlets. The top and bottom inlets are for oil with dissolved lipids, which are used to form the lipid bilayer membrane. The middle inlet will contain water with the drug, which will be encapsulated in the bilayer membrane. The material properties of the lipids allow for the assembly of a spherical shape, which is known as the nanoparticle. A schematic of the process is shown below.
The nanoparticle is made of several components, which is detailed out in the image below. The lipid bilayer, like the name suggests, is made up of two layers. Each layer has a hydrophilic (loves water) head and a hydrophobic (hates water) tail. The center of the nanoparticle contains the drug in water; this is why the hydrophillic heads are in contact with the center; the environment outside of the nanoparticle is also water based. the hydrophobic tails of each lipid layer are in contact in the center of the lipid bilayer membrane.
The nanoparticles are also coated with proteins or fatty acids to target specific locations or organs in the body. The sugars are coated on the surface to prevent the immune system from destroying the nanoparticle; however, a better membrane coating will be more effective for this situation.
The nanoparticles are also coated with proteins or fatty acids to target specific locations or organs in the body. The sugars are coated on the surface to prevent the immune system from destroying the nanoparticle; however, a better membrane coating will be more effective for this situation.
https://sitn.hms.harvard.edu/sitnflash_wp/category/cancer/
Difficulties in this area of Research
Professor Theogarajan's background is in Electrical Engineering and he is a professor in the Department of Electrical and Computer Engineering; in many people's eyes, drug delivery research does not fall under this discipline. Professor Theogarajan has encountered difficulties in finding funding for his drug delivery research when he is competing with other researchers who are in more closely related fields.
Some technical difficulties in this area are making the devices for the nanoparticles and coating the surface of the particles to attract to cells. Also, this research must be animal tested before it can be used in human clinical trials; however, animal testing is often extremely expensive.
Some technical difficulties in this area are making the devices for the nanoparticles and coating the surface of the particles to attract to cells. Also, this research must be animal tested before it can be used in human clinical trials; however, animal testing is often extremely expensive.
Future Directions
Professor Theogarajan will continue to develop new membrane materials to replace the PEG coating for the nanoparticles to have more effective cancer treatments. This is technology to treat cancer; however, further down the road, he would like to work in gene delivery, which can help prevent cancer and other diseases.
Other future directions associated with this research are developing methods and materials that will allow for this treatment to be more affordable for patients; this deals with using polymer membranes instead of lipid membranes. Professor Theogarajan anticipates site-specific drug delivery to reach the bed-side in 5-10 years and that it will probably be much cheaper than the current method of cancer treatment; however, a substantial percentage of the costs associated with the treatment will be in testing and regulatory requirements.
Other future directions associated with this research are developing methods and materials that will allow for this treatment to be more affordable for patients; this deals with using polymer membranes instead of lipid membranes. Professor Theogarajan anticipates site-specific drug delivery to reach the bed-side in 5-10 years and that it will probably be much cheaper than the current method of cancer treatment; however, a substantial percentage of the costs associated with the treatment will be in testing and regulatory requirements.
For more information about Professor Theogarajan's research, please visit the Biomimetic Circuits and Nanosystems Group Webpage.
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Selected Publications
Isaacman, M. J., Barron, K. A. and Theogarajan, L. S. (2012), Clickable amphiphilic triblock copolymers. J. Polym. Sci. A Polym. Chem., 50: 2319–2329. doi: 10.1002/pola.25989
Borjigin, N; Theogarajan, L, Novel ABA triblock copolymers with pendent carboxylic acid side chain for drug delivery systems, Abstracts of Papers of the American Chemical Society, 2010, N502.
L. Theogarajan, S. Desai, M. A. Baldo and C. Scholz, Versatile Synthesis of Self-assembling ABA Triblock copolymers with Polymethyloxazoline A-blocks and a Polysiloxane B-block Decorated with Supramolecular Receptors, Polymer International, 57, pp. 660-667, 2008.
Borjigin, N; Theogarajan, L, Novel ABA triblock copolymers with pendent carboxylic acid side chain for drug delivery systems, Abstracts of Papers of the American Chemical Society, 2010, N502.
L. Theogarajan, S. Desai, M. A. Baldo and C. Scholz, Versatile Synthesis of Self-assembling ABA Triblock copolymers with Polymethyloxazoline A-blocks and a Polysiloxane B-block Decorated with Supramolecular Receptors, Polymer International, 57, pp. 660-667, 2008.