Nanotechnology, which involves the ability to manipulate individual atoms and molecules, is being heralded as the future of medical science. The fabrication of nanoscale materials has already begun to revolutionize injectable medicines, especially in cancer and critical care, by enabling:

• Direct intervention in the human body using smart operating elements that are so small (there are 25.4 million nanometers in one inch) they do not physically interfere with normal body function
• Development of novel therapies and devices that may reduce toxicity and enhance the efficacy and delivery of treatments
• Enhanced formulations of chemotherapeutics and other medicines that can reduce infection risks and improve patient safety and quality of life
• Improving treatment administration, especially when time is of the essence

Nanotechnology for Drug Delivery

Drug delivery is the most widely applied use of nanotechnology in medicine, typically as an alternative to conventional chemotherapy. The use of nanoparticles as drug carriers for chemotherapeutics has several advantages over conventional chemotherapy injections. These include:

• Reduction of the impact of drugs interacting with normal cells, which can amielorate adverse side effects such as neuropathy, hair loss, fatigue, hematologic toxicity, and compromised immune function
• Protection of drugs from being degraded in the body before they reach their target
• Enhancement of the absorption of drugs into tumors and into the cancerous cells themselves
• Allowing for better control over the timing and distribution of drugs to the target tissue, which makes it easier for oncologists to assess how well treatment works

Nanotechnology-based therapeutics can address some of the major challenges associated with existing cancer treatments, including drug toxicity and tumor resistance. Toxicity can cause major complications, such as low–white-blood cell counts or heart failure, which necessitate stopping therapy. And the evolution of drug resistance by tumors accounts for the vast majority of cases in which treatment fails.

Nanotechnology-based cancer drugs such as Doxil® and Abraxane® have been on the market for more than a decade. In recent years, the U.S. Food and Drug Administration (FDA) has accepted numerous Investigational New Drug (IND) applications for nanoformulations, enabling clinical trials for breast, gynecological, solid tumor, lung, mesenchymal tissue, lymphoma, central nervous system, and genito-urinary cancer treatments.

These and other applications take advantage of nanoparticles’ enhanced properties, which include higher strength, lighter weight, increased control of light spectrum, and greater chemical reactivity than their larger-scale counterparts.

Enhanced Formulations of Chemotherapeutics and Other Injectable Medicines

Another nano-enhanced drug delivery application that capitalizes on these characteristics is the reformulation of injectable medicines for both cancer and critical care. By providing physicians and nurses with appropriately sized and easy-to-use medicines, these formulations can help reduce waste and dosing errors while improving contamination control practices, safety, and treatment efficacy. 

For example, many injectable cancer medicines are packaged in small vials and come in formulations that require reconstitution or dilution. Each time a vial seal must be punctured or a drug has to be reconstituted or diluted heightens the risk of infection and dosing errors that can diminish a drug’s efficacy. According to the FDA, “the need to combine several single-dose vials for a single patient dose may lead to medication errors and microbial contamination.”¹

Advances in nanotechnology are now empowering manufacturers of injectable cancer medicines to develop more purely soluble formulations capable of delivering more of the drug in smaller volumes. This not only reduces the potential for medication errors and infection risks associated with the use of multiple vials but also can improve cancer patients’ quality of life.

For example, patients often receive multiple chemotherapy medications, which are administered in consecutive same-day intravenous infusion, and sometimes must spend up to eight hours in the treatment clinic or doctor’s office. The recently FDA-approved injectable BENDEKA™ (bendamustine hydrochloride), a liquid formulation, requires low-volume (50 mL) admixture and reduces infusion time for patients to 10 minutes² from 30-60 minutes.

Nanotechnology medicines also are being used in critical care for malignant hyperthermia, a pharmacogenomics disease that can be caused by a reaction to anesthesia during surgery and can be fatal if not quickly treated. Treatment typically requires healthcare personnel to reconstitute 12 or more 20-mg vials of dantrolene sodium, which require about 700 mL of intravenous diluent and can take as long as 15 to 20 minutes to prepare and administer. Today, a nanoparticle-optimized formulation called RYANODEX® (dantrolene sodium) for injectable suspension³ requires just one vial (250 mg) for most patients and 5 mL of diluent. This medicine can be prepared and administered in less than a minute.

Inside the Death Star

Many of the latest developments in cancer care are using nanotechnology to deliver innovative therapies inside the tumor. Instead of activating normal molecular mechanisms to induce cell death, researchers are exploring ways to physically destroy cancerous cells from within.

Although metastases of cancers in the lung and liver are the primary causes of cancer deaths, existing cancer drugs often are of limited power because the body’s protective biological barriers prevent chemotherapy drugs from reaching their intended targets in high enough concentrations. A new method developed at the Houston Methodist Research Institute used an injectable nanoparticle generator to successfully penetrate these biological defenses and was able to make and release its drug nanoparticles at the site of the cellular nucleus.⁴

Other potential new therapeutic approaches using nanotechnology in creative ways include:

• Another technology that destroys cancer cells inside the “Death Star” deploys nanoshells⁴ designed to absorb light of different frequencies and generate heat (hyperthermia). Scientists apply near-infrared light to these nanoshells once they are inside the tumor to create an intense heat that selectively kills tumor cells without disturbing neighboring healthy cells.⁵
• One nanotherapy platform functions as a tumor-targeted Trojan horse to enter tumors through their most vulnerable points—the leaky blood vessels that make up the nutritional support structures. It then selectively binds tumor necrosis factor receptors on blood vessel cells at the site of disease and unleashes a therapeutic payload that destroys the tumor’s nutritional support structures and protective barriers.⁶
• Using a nanoparticle that delivers a drug and then fluoresces green when cancer cells begin dying, researchers have been able to visualize whether or not a tumor is resistant or susceptible to a particular treatment much sooner than with currently available clinical methods.⁷
• These and numerous other nanotechnology applications now in development have virtually unlimited potential to lead to breakthrough advances in the prevention, detection, and treatment of cancer and other diseases.

References

1. Dangi-Garimella S. Size Matters When It Comes to Cancer Drug Vials and Healthcare Waste, Says BMJ Study. AJMC.com. March 1, 2016. http://www.ajmc.com/newsroom/size-matters-when-it-comes-to-cancer-drug-vials-and-healthcare-waste-says-bmj-study.
2. FDA Approves Bendeka. Teva Pharmaceuticals and Eagle Pharmaceuticals Announce FDA Approval of BENDEKA™ (bendamustine hydrochloride) Injection [press release]. Drugs.com. December 8, 2015. http://www.drugs.com/newdrugs/teva-pharmaceuticals-eagle-pharmaceuticals-announce-fda-approval-bendeka-bendamustine-hydrochloride-4311.html.
3. RYANODEX® (dantrolene sodium) for injectable suspension. Eagle Pharmaceuticals. http://www.eagleus.com/products/dantrolene-sodium.
4. Newman T. Injectable nanoparticles show ‘astounding’ prowess against cancer. Medical News Today. March 15, 2016. http://www.medicalnewstoday.com/articles/307853.php.
5. National Nanotechnology Initiative, National Cancer Institute. Nano.gov. http://www.nano.gov/node/604.
6. CytImmune. Aurimune: A Nanomedicine Platform. http://www.cytimmune.com.
7. New nanoparticle reveals cancer treatment effectiveness in real time. Brigham and Women’s Hospital. April 1, 2016. MDLinx.com. http://www.mdlinx.com/oncology/top-medical-news/article/2016/04/01/11?trendmd-shared=1.

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