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New method may allow breast cancer drug to be given through skin

Date:
July 10, 2014
Source:
University of Illinois at Chicago
Summary:
Endoxifen, a drug that has proven effective in the prevention and treatment of breast cancer, but with serious side-effects, may be delivered effectively through the skin using a new topical drug-delivery system. Endoxifen, one of the most commonly used hormone therapy for breast cancer, has also been shown to prevent the disease. However, taken orally, the drug can cause side-effects such as hot flashes and vaginal atrophy, along with increased risk of endometrial cancer and stroke, that leave it wanting as a routine method of chemoprevention.

Seungpyo Hong, assistant professor of pharmaceutics and bioengineering.
Credit: Image courtesy of University of Illinois at Chicago

A drug that has proven effective in the prevention and treatment of breast cancer, but with serious side-effects, may be delivered effectively through the skin using a new topical drug-delivery system.

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Endoxifen, one of the most commonly used hormone therapy for breast cancer, has also been shown to prevent the disease. However, taken orally, the drug can cause side-effects such as hot flashes and vaginal atrophy, along with increased risk of endometrial cancer and stroke, that leave it wanting as a routine method of chemoprevention.

University of Illinois at Chicago researchers, in collaboration with Northwestern University clinicians, developed a chemical encapsulation for endoxifen and showed in laboratory studies that it may be better than some other techniques used to help the drug cross the skin barrier. The study was published in the journal Advanced Functional Materials in May.

Delivering the drug directly through the breast may reduce the number of mastectomies while lessening the side-effects of oral endoxifen, says Seungpyo Hong, assistant professor of pharmaceutics and bioengineering at UIC and lead author of the paper.

Endoxifen, a more active form of its chemical-cousin tamoxifen, must cross multiple layers of skin to reach the site where it can prevent breast cancer, Hong said. The drug cannot pass through skin layers without the use of penetration enhancers.

Hong and his colleagues created dendron-based micelles -- essentially, specialized bubbles -- to encapsulate endoxifen. They used hairless mouse and human skin samples to test the package's ability to cross the skin barrier as compared to unencapsulated endoxifen.

"We found that dendron micelles can achieve sufficient loading, enhanced skin permeation, and controlled release of endoxifen, without losing its efficacy, compared to free endoxifen," Hong said.

A water-soluble drug formulation used by the researchers allowed the dendron micelles to deliver endoxifen without the use of chemical penetration enhancers like alcohol or detergent, Hong said. These small molecules, which make the skin more permeable, may cause irritation.

The size of the micelle can determine how easily endoxifen permeates the skin, Hong said, and whether it causes irritation. Compared to ethanol and cationic liposomes, the smaller size of micelles (40 to 50 nanometers, versus 100 nm for the liposomes) creates a greater surface-to-volume ratio.

Comparing the speeds at which the different methods carried endoxifen across the skin, the researchers found that cationic liposomes transmitted the drug faster but without stably encapsulating the drug. Although slower, the dendron micelles released the drug in a more controlled manner -- a potential advantage, Hong said, for a drug intended for chemoprevention.

"Given that the target recipients are those who have the potential to develop breast cancer, a slow-release system could reduce dosing frequency, which would significantly increase the patient compliance," he said.


Story Source:

The above story is based on materials provided by University of Illinois at Chicago. The original article was written by Sam Hostettler. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yang Yang, Ryan M. Pearson, Oukseub Lee, Chan-Woo Lee, Robert T. Chatterton, Seema A. Khan, Seungpyo Hong. Drug Delivery: Dendron-Based Micelles for Topical Delivery of Endoxifen: A Potential Chemo-Preventive Medicine for Breast Cancer (Adv. Funct. Mater. 17/2014). Advanced Functional Materials, 2014; 24 (17): 2441 DOI: 10.1002/adfm.201470109

Cite This Page:

University of Illinois at Chicago. "New method may allow breast cancer drug to be given through skin." ScienceDaily. ScienceDaily, 10 July 2014. <www.sciencedaily.com/releases/2014/07/140710183433.htm>.
University of Illinois at Chicago. (2014, July 10). New method may allow breast cancer drug to be given through skin. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2014/07/140710183433.htm
University of Illinois at Chicago. "New method may allow breast cancer drug to be given through skin." ScienceDaily. www.sciencedaily.com/releases/2014/07/140710183433.htm (accessed October 25, 2014).

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