Billionths of a Meter Cancer Drugs

Nanomedicine and antiangiogenesis vascular modeling

(RxWiki News) Nanomedicine is the latest answer to the ancient dilemma of finding the best way to deliver a drug. Skipping the stomach with intravenous drugs is one shortcut, but getting a drug from the bloodstream into a cell is even more complicated.

Nanomedicine uses small molecules that are able to go anywhere in the body and have no problems entering cells freely, unlike normal drugs.

In one study comparing the use of standard chemotherapy with the experimental technique of nanomedicine, a group of scientists found that they could influence the size of particles that reached the tumor.

"Ask your oncologist about nanomedicine."

In a recent laboratory experiment conducted at Massachusetts General Hospital (MGH), led by Vikash P. Chauhan, mice containing human breast cancer tumors were given several nanomedicines of different sizes. Another drug was given to the mice that changed the blood vessels, which made it harder for nanomedicines to leave the bloodstream in selected areas.

A leading cause of treatment failure in many cancers is the ability of tumor cells to change their plasma membrane, preventing chemotherapy drugs from entering the cell like they used to. This problem would be avoided entirely by the use of nanomedicines, since they move freely into cells due to their small size and lack of electrical charge.

Precise control over how and where nanomedicines go is one of the last remaining problems in the field before widespread use can be adopted. Despite this, the rewards would be immense, and interest in the field has been intense.

Two nanomedicines developed for use in chemotherapy are Doxil (doxorubicin) and Abraxane (paclitaxel). In the study performed on human breast cancer cells implanted in mice, Doxil, at 100 nanometers, and Abraxane, at 10 nanometers, were given to the mice.

Both treatments showed that the drugs remained effective, tumor growth was delayed, and most importantly, that blood vessels could be altered to only deliver drugs of a certain size. In this experiment, blood vessel treatment improved the effect of Abraxane, and Doxil stayed at the same level of effectiveness as in previous tests.

As a point of reference, a nanometer is a billionth of a meter.

To get a sense of scale, if you imagine a small virus as the size of a person, a nanometer would be the size of a soccer ball. Medical application of this principle has been fascinating, as any drug that small would slide right through cellular membranes, avoiding many, many problems involved in creating an effective drug.

The field of nanotechnology has received a lot of press but not a lot of real application due to the problems with things that small. Normally ignored because they are so weak, molecular forces become real problems. Concern about problems due to inhalation of the tiny particles has also been raised.

Nanomedicines such as Doxil and Abraxane are also known as liposome encapsulated versions of the parent drug. This liposome coat allows the drug to pass through cellular membranes freely by making it neutrally charged and, in addition to being incredibly small, allows it to go anywhere in the body.

Unfortunately one of the consequences of such freely moving tiny molecules results in small amounts of the drug appearing in sweat. In chemotherapy, this can cause a skin reaction in vessel-heavy areas like hands and feet. The hope of researchers is that using drugs to change the blood vessels selectively may be the first step to solving that problem.

The lead author, Vikash Chauhan, concluded that the relationship between drug size and blood vessel property needed further study for best drug delivery.

"Our findings suggest that combining smaller nanomedicines with anti-angiogenic therapies may have a synergistic effect and that smaller nanomedicines should inherently penetrate tumors faster than larger nanomedicines, due to the physical principles that govern drug penetration.

"While it looks like future development of nanomedicines should focus on making them small – around 12 nanometers in size – we also need to investigate ways to improve delivery of the larger nanomedicines that are currently in use."

Cost of a single dose of Doxil was quoted at $31,000 as recently as 2010.

The results of the experiments were published online in the journal Nature Nanotechnology on April 8, 2012.

Researchers and study authors denied any financial conflict of interest in the publication of the study.

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Review Date: 
April 12, 2012