Scientist finds genetic wrinkle to block sun-induced skin aging

UBC researchers created a device to act as a tanning bed for mice. Credit: Image courtesy of University of British Columbia

A scientific team at UBC and Providence Health Care have genetically engineered mice with less wrinkled skin, despite repeated exposure to wrinkle-inducing ultraviolet (UV) light.

The findings, published last week in Aging Cell, raises hope for a drug that would block the activity of Granzyme B in certain places, and thus prevent the aging and deterioration of tissues that depend on collagen -- not just skin, but blood vessels and lung passages.

viDA Therapeutics, a company co-founded by David Granville, a professor in the Department of Pathology and Laboratory Medicine and a principal investigator in the Centre for Heart Lung Innovation of UBC and St. Paul's Hospital, is currently developing a Granzyme-B inhibitor based on technology licensed from UBC. The company plans to test a topically applied drug within two years on people with discoid lupus erythematosus, an autoimmune disease worsened by sunlight that can lead to disfiguring facial scarring. (The musician Seal has such a condition.)

If the drug proves effective in preventing lupus-related skin lesions, there is potential for a cosmetic product to prevent the normal, gradual aging of the skin, which is mostly caused by sun exposure. But the drug might also be used for life-threatening conditions, such as aneurysms and chronic obstructive pulmonary disease, caused by the breakdown of collagen and other proteins that provide structure to blood vessels and lung passages.

Background

A serendipitous discovery: Granville was investigating the role of Granzyme B in atherosclerosis and heart attacks. He and his team wanted to see if the blood vessels of mice lacking Granzyme B were more resistant to hardening and narrowing, which is a major cause of heart attacks in human. In the process, they discovered that such mice retained youthful-looking skin compared to the aged skin on normal mice.

The Canadian Institutes of Health Research (CIHR), Genome BC, and Mitacs financially support this research.

An experimental tanning bed: Granville's team constructed a device to simulate sun exposure on mice. Each mouse was put in a carousel that slowly turned under UV lamps, exposing them for three to four minutes, three times a week -- enough to cause redness, but not to burn. After 20 weeks of repetitive exposure, it became clear that the skin of mice lacking Granzyme B had aged much less -- and their collagen was more intact -- compared to the control groups.

Source: University of British Columbia

Novel microneedle patch for faster, effective delivery of painkiller, collagen

Dr Kang Lifeng of the Department of Pharmacy at NUS holding a microneedle patch in his left hand, and a photomask in his right hand. Credit: National University of Singapore

Individuals who are squeamish about injections or are looking for a way to let collagen penetrate deeper into the skin may soon have a solution that is faster, more effective and painless. The key lies in a small adhesive patch topped with minuscule needles that is pioneered by researchers from the National University of Singapore (NUS).

The research team, led by Dr Kang Lifeng of the Department of Pharmacy at the NUS Faculty of Science, has successfully developed a simple technique to encapsulate lidocaine, a common painkiller, or collagen in the tiny needles attached to an adhesive patch. When applied to the skin, the microneedles deliver the drug or collagen rapidly into the skin without any discomfort to the user.

This innovation could be used clinically to administer painkiller non-invasively to patients, or in home care settings for patients suffering from conditions such as diabetes and cancer. In addition, the novel transdermal delivery system could also be used for cosmetic and skincare purposes to deliver collagen to inner skin layers.

Non-invasive delivery of drugs for effective pain relief

Faster delivery of painkillers is key to effective management of acute and chronic pain conditions. Currently, such drugs are mainly administered through invasive injections, or through the use of conventional transdermal patches, which may have limited efficiency due to variability of drug absorption among individuals.

To address the clinical gap, Dr Kang, together with Dr Jaspreet Singh Kochhar, who had recently graduated from NUS with a doctorate degree in Pharmacy, and their team members, used a photolithography based process to fabricate a novel transdermal patch with polymeric microneedles. The tiny needles are encapsulated with lidocaine, a common painkiller known for its pain-relief property.

Laboratory experiments showed that the novel microneedles patch can deliver lidocaine within five minutes of application while a commercial lidocaine patch takes 45 minutes for the drug to penetrate into the skin. The shorter time for drug delivery is made possible as the miniature needles on the patch create micrometre-sized porous channels in the skin to deliver the drug rapidly. As the needle shafts are about 600 micro-meters in length, they do not cause any perceivable pain on the skin.

The patch also comprises a reservoir system to act as channels for drugs to be encapsulated in backing layers, circumventing the premature closure of miniaturised pores created by the microneedles. This facilitates continued drug permeation. In addition, the size of patch could be easily adjusted to encapsulate different drug dosages.

By delivering painkillers faster into the body through the skin, patients could potentially experience faster pain relief. In addition, enabling a larger amount of lidocaine to permeate through the skin could potentially reduce the time needed to apply the patch and this reduces the likelihood of patients developing skin irritation.

This novel technique was first reported in the scientific journal Molecular Pharmaceutics.

Enabling deeper penetration of collagen into the skin

To expand their research on potential applications of the microneedles patch, the NUS team 
conducted a study to explore its effectiveness in delivering collagen into skin.

The researchers encapsulated collagen in the microneedles and tested the transdermal delivery of collagen using the novel technique. They found that collagen can be delivered up to the dermis layer of the skin, while current skincare products can only deliver to the outermost layer of skin.

The findings of this study were first published earlier this year in the scientific journal Pharmaceutical Research.

Further research to expand application of novel microneedles patch

As their novel technique for drug delivery is non-invasive and easy to use, the NUS team envisioned that the microneedles patch has great potential for applications in clinical and home care settings for the management of perioperative pain and chronic pain in patients suffering from conditions like diabetes and cancer.

The innovative patch could also have pediatric applications. Dr Kang explained, "One prospective application is during vaccination for babies. The patch can be applied on the baby's arm five minutes before the jab, for the painkiller to set in. In this way, vaccination can potentially be painless for babies."

The research team intends to conduct clinical testing of the painkiller patch to further ascertain its effectiveness for clinical applications. They will also be conducting clinical studies to examine the efficacy of delivering collagen for cosmetic and skincare purposes.
Recognizing that their novel transdermal delivery system is easy to fabricate and commercially scalable, the research team is also keen to work with industry partners to commercialize their work.

Source: National University of Singapore