NEWS |
CANCER DRUG COULD BE APPLIED TOPICALLY
NEW DELIVERY SYSTEM FOR BREAST CANCER DRUG
effectively through the skin using a new topical drug-delivery system. Endoxifen, one of the most commonly used
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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 flushes 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 (UIC) 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.
drug that has proven effective in the prevention and treatment of breast cancer, but with serious side-effects, may be delivered
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. 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, and whether it causes irritation. Compared to ethanol and cationic liposomes, the smaller size of micelles (40 to 50 nm, versus 100 nm for the liposomes) creates a greater surface-to-volume ratio.
Delivering the drug directly through the breast may reduce the
Skin penetration enhancers 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, specialised bubbles — to encapsulate endoxifen. They used hairless mouse and human skin samples to test
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number of mastectomies while lessening the side-effects of oral endoxifen.
Drug transmission 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. The research was funded in part by the Susan
G. Komen Foundation under grant number KG100713. Co-authors are Yang Yang and Ryan Pearson of UIC; Drs Oukseub Lee, Seema Khan and Robert Chatterton, Jr., of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University; and Chan-Woo Lee of the Durae Corporation in Gunpo, South Korea.
July/August 2014 |
prime-journal.com
SANDALWOOD SCENT FOR SKIN REPAIR
Skin cells possess an olfactory receptor for sandalwood scent, researchers at the Ruhr-Universität Bochum (RUB) have discovered. Their data indicate that the cell proliferation increases and wound healing improves if those receptors are activated. This mechanism constitutes a possible starting point for new drugs and cosmetics. The team headed by Dr Daniela Busse and Prof Dr Dr Dr med habil Hanns Hatt from the Department for Cell Physiology published their report in the Journal of Investigative Dermatology. Humans have approximately 350 different types of olfactory receptors in the nose. The function of those receptors has also been shown to exist in, for example, spermatozoa, the prostate, the intestine, and the kidneys. The team from Bochum has now discovered them in keratinocytes — cells that form the outermost layer of the skin.
Experiments with cultures of human skin cells The RUB researchers studied the olfactory receptor that occurs in the skin, namely OR2AT4, and discovered that it is activated by a synthetic sandalwood scent, so-called Sandalore. Sandalwood aroma is frequently used in incense sticks and is a popular component in perfumes. The activated OR2AT4 receptor triggers a calcium- dependent signal pathway. That pathway ensures an increased proliferation and a quicker migration of skin cells — processes which typically facilitate wound healing. In collaboration with the Dermatology Department at the University of Münster, the cell physiologists from Bochum demonstrated that effect in skin cell cultures and skin explants. In addition to OR2AT4, the RUB scientists
have also found a variety of other olfactory receptors in the skin, the function of which they are planning to characterise more precisely. ‘The results so far show that they possess therapeutic and cosmetic potential,’ says Prof Hanns Hatt. ‘Still, we mustn’t forget that concentrated fragrances should be handled with care, until we have ascertained which functions the different types of olfactory receptors in skin cells have.’
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