Nanotechnology in Drug Delivery

If your drug use consists of an occasional aspirin, you may not see the need for serious work on drug delivery. But if you were diabetic, having to inject insulin several times a day, or a cancer patient experiencing debilitating side effects from your treatment, the benefits of improved drug delivery could change your life.

Perhaps the most publicized use of nanotechnology in drug delivery under development is the use of nanoparticles to deliver drugs to cancer cells. Particles are engineered so that they are attracted to diseased cells, which allows direct treatment of those cells. This technique reduces damage to healthy cells in the body.

However, that’s just the tip of the drug delivery iceberg: there are a number of other ways that nanotechnology can make the delivery of drugs more efficient and potentially less unpleasant for the patient. Some techniques are only imagined, while others are at various stages of testing, or actually being used today. The following survey of nanomedicine applications in drug delivery introduces many of these techniques.

Nanotechnology in Drug Delivery - Cancer:

Many researchers attach ethylene glycol molecules to nanoparticles that deliver therapeutic drugs to cancer tumors. The ethylene glycol molecules stop white blood cells from recognizing the nanoparticles as foreign materials, allowing them to circulate in the blood stream long enough to attach to cancer tumors. However researchers at the University of California, San Diego believe that they can increase the time nanoparticles can circulate in the blood stream. They are coating nanoparticles containing therapeutic drugs with membranes from red blood cells and have shown that these nanoparticles will circulate in a mouse's blood stream for almost two days, instead of the few hours observed for nanoparticles using ethylene glycol molecules.

Researchers are also continuing to look for more effective methods to target nanoparticles carrying therapeutic drugs directly to diseased cells. For example scientists are MIT have demonstrated increased  levels of drugs delivery to tumors by using two types of nanoparticles. The first type of nanoparticle locates the cancer tumor and the second type of nanoparticle (carrying the therapeutic drugs) homes in on a signal generated by the first type of nanoparticle.

Researchers at University College London are testing the use of DNA to construct pores in which drug molecules can be carried. The researchers think this technique may allow more precise delivery of drug molecules to diseased cells.    

Researchers at Oregon State University are developing nanoparticles that deliver three anti-cancer drugs to the lymp nodes. The intent is to target cancers that use the lymp nodes to spread through the body. Testing of this technique, so far, has been with lab animals.

Researchers at the Institute of Bioengineering and Nanotechnology and IBM researchers have demonstrated sustained drug delivery using a hydrogel. The hydrogel is injected under the skin, allowing continuous drug release for weeks, with only one injection, rather than repeated injections. They demonstrated this method by injecting the hydrogel, containing the chemotherapy drug herceptin, under the skin of laboratory mice. The study showed significant reduction in tumor size.

Other researchers are using a photosensitizing agent to enhance the ability of drug carrying nanoparticles to enter tumors. First they let the photosensitizing agent accumulate in the tumor, then illuminate the tumor with infrared light. The photosensitizing agent causes the blood vessels in the tumor to be more porous, therefore more drug carrying nanoparticles can enter the tumor.

Two researcher groups have been focused on the best shape of nanoparticle to use for delivering drugs to cancer tumors. One research group has found that a disk shaped nanoparticle (nanodisk) will stick to the surface of a tumor longer than a spherical shaped nanoparticle, providing more efficient transfer of therapeutic drugs to the tumor. Another set of researchers have found that  rod shaped nanoparticles are more effective at delivering chemotherapy drugs to breast cancer cells than spherical nanoparticles.

Using gold nanoparticles to deliver platinum to cancer tumors may reduce the side effects of platinum cancer therapy. The key is that the toxicity level of platinum depends upon the molecule it is bonded to (for the tech types the toxicity depends upon the oxidation state of the platinum). So the researchers chose a platinum containing molecule that has low toxicity to attach to the gold nanoparticles. When the platinum bearing nanoparticle reaches a cancer tumor it encounters an acidic solution which changes the platinum to it's toxic state, in which it can kill cancer cells. For more details read the article at this link

Using nanoparticles to deliver nitric oxide directly to cancer cells may reduce the required amount of chemotherapy drugs. Researchers conducting tests on neuroblastoma cancer cells found that the effectiveness of the chemotherapy drug was increased 5 times when nanoparticles were used to deliver nitric oxide directly to the cancer cells.

Other researchers are taking a different approach to delivering platinum to cancer tumors. Instead of attaching platinum to nanoparticles they have used molecular building blocks to produce nanoparticles designed to deliver platinum to cancer tumors.  For more details read the article at this link.

A method being developed to fight skin cancer uses gold nanoparticles to which RNA molecules are attached. The nanoparticles are in an ointment that is applied to the skin. The nanoparticles penetrate the skin and the RNA attaches to a cancer related gene, stopping the gene from generating proteins that are used in the growth of skin cancer tumors.

Reseachers have developed elastic materials embedded with needle like carbon nanofibers. The material is intended to be used as balloons which are inserted next diseased tissue, and then inflated. When the balloon is inflated the carbon nanofibers penetrate diseased cells and delivery therapeutic drugs.

More info on the use of Nanotechnology in Cancer Treatment

Nanotechnology in Drug Delivery - Heart Disease:

Researchers at Clemson University have developed a nanoparticle that uses a protein to attach to damaged regions of arteries. This allows drugs to be applied directly to the damaged portion of the artery.

Lab studies in mice have shown that using nanoparticles to target the delivery of the clot busting drug tPA can reduce the dosage of tPA needed, which may reduce possible side affects, such as internal bleeding.  The clot busting drug was attached to a cluster of nanoparticles that break apart in regions of turbulent blood flow, like that found when a blood flow is restricted by a clot.

Researchers are developing polymer nanoparticles that home in on inflamed tissue such as arterial plaque and dissolve, releasing drugs, in the presence of hydrogen peroxide that is present in the inflamed tissue.

Nanoparticles containing iron oxide that allows the nanoparticles to be directed, by a magnetic field, to stents. This could allow drugs to be delivered directly to stents placed in arteries.

More info on applications of Nanotechnology to Heart Disease

Nanotechnology in Drug Delivery - Aging and other areas

Drugs to treat glaucoma is being attached to nanodiamonds which are embedded in contact lenses. The drug molecules are released from the nanodiamonds are in contact with tears, providing a more consistent dosing than often occurs using eye drops.

Researchers are improving dental implants by adding nanotubes to the surface of the implant material. They have demonstrated to the ability to load the nanotubes with anti-inflammatory drugs that can be applied directly to the area around the implant. As well they have shown that bone adheres better to titanium dioxide nanotubes than to the surface of standard titanium implants.

Researchers have developed nanoparticles that release insulin when glucose levels rise. The nanoparticles contain both insulin and an enzyme that dissolve in high levels of glucose. When the enzyme dissolves the insulin is released. In lab test these nanoparticles were able to control blood sugar levels for several days.

Another method being developed to release insulin uses a sponge-like matrix that contains insulin as well as nanocapsules containing an enzyme. When the glucose level rises the nanocapsules release hydrogen ions, which bind to the fibers making up the matrix. The hydrogen ions make the fibers positively charged, repelling each other and creating openings in the matrix through which insulin is released.

A method being developed to tackle autoimmune diseases uses nanoparticles to deliver antigens for a particular disease into the blood stream. The antigens reset the immune system, stopping white blood cells from attacking healthy cells. This method has been tested in the lab on mice with a disease similar to multiple sclerosis with promising results.

Researchers are developing nanoparticles that can delivery drugs across the brain barrier to tackle neurologic disorders.

A method being developed to fight aging uses mesoporous nanoparticles with a coating that releases the contents of the nanoparticle when an emzyme found in aging cells is present.

Skin creams that uses proteins derived from stem cells to prevent aging of the skin. These proteins are encapsulated in liposome nanoparticles which merge with the membranes of skin cells to allow delivery of the proteins.

Researchers have developed a nanoparticle that can slip through mucus coating surfaces such as lung tissue. This ability to penetrate the mucus coating should provide the capability to coat lung tissue with therapeutic drugs.

Medical implants made of porous plastic, coated with carbon nanotubes. Therapeutic drugs, which are attached to the nanotubes can be released into the bloodstream, for example, when a change in the blood chemistry signals a problem. NASA is developing these implants, called  a "biocapsule", to protect astronauts from the effects of radiation however the implants may also be useful for releasing insulin for diabetes patients or for delivering chemotherapy drugs directly to tumors.

Compiled by Earl Boysen of Hawk's Perch Technical Writing, LLC and UnderstandingNano.com. You can find him on Google+.


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