The skin provides vital protection against the external environment but also acts as a barrier for delivering medicine. Researchers have developed a technique that generates channels in the skin to enhance the penetration of topically applied drugs. Initial experiments in treating people with skin cancer are promising. Future perspectives for laser-assisted drug delivery are numerous and, for some diseases, the technique may prove to be more effective than injection or oral medication.
The key to curing people with disease is ensuring that medicine selectively reaches the cells affected by the disease. Traditionally, most medicine is given orally, which typically requires getting the active ingredient to cross the intestinal barrier or through injections and intravenous drip, which introduces the drugs directly into the tissue or bloodstream. Transdermal delivery avoids the pitfalls of pills, in which much of the active ingredient is lost as it crosses the intestinal barrier or is broken down by the liver. In addition, in treating people with a local disease such as skin cancer, the advantage of reducing the body’s exposure to drugs and their side-effects is key. Researchers have therefore developed a laser technique that improves the delivery of medicine directly through the skin’s surface.
“Drug penetration through intact skin is often limited by the size, charge and solubility of the molecules in a specific drug. In collaboration with the Wellman Center for Photomedicine at Massachusetts General Hospital in Boston, USA, we have shown that the delivery of anticancer agents into skin can be significantly enhanced. Ultimately, the techniques’ applicability extends to a broad range of skin disorders and, potentially, systemic conditions,” explains Emily Catherine Wenande, PhD student, Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg and Frederiksberg Hospital, Copenhagen.
Local combination chemotherapy
The researchers used skin from live pigs to examine whether chemotherapeutic (anticancer) agents can be delivered across the skin barrier. Light from an ablative fractional laser targets water in the skin, creating microscopic holes through the skin surface, thereby increasing its permeability.
“This technique creates hundreds of channels in the skin, enabling chemotherapeutic agents to reach their intended targets beneath the upper skin layers. Our group was interested in using affordable anticancer agents with proven efficacy against non-melanoma skin cancer. Two such agents, cisplatin and 5-FU (5-fluorouracil), are known to enhance each other’s action when used in combination. However, they penetrate the skin barrier relatively poorly."
They hoped to take advantage of their combined effects by delivering both cisplatin and 5-FU directly into the skin using their laser-based delivery technique.
“When we delivered the two drugs in combination in live pigs, their inhibitory effects occurred more rapidly and were more pronounced. Within a couple of days, exposed skin sites developed wounds, and measurements of drug concentrations confirmed higher drug levels in laser-treated skin. These results were exactly what we hoped to see.”
A new way to treat skin disease
After succeeding in combining the laser technique with the two chemotherapeutic agents, the researchers are now testing the treatment on people with basal cell carcinoma. This type of skin cancer is almost never fatal. However, it can be highly debilitating since people often develop multiple lesions, endure a high degree of recurrence and are commonly affected in delicate facial areas. The researchers hope that they can treat people with this type of skin cancer using the new treatment.
“Currently, basal cell carcinoma is either treated surgically, by radiation or, for more superficial lesions, using topical therapies. However, not everyone is a good candidate for surgery, and mutilating scarring and recurrence remain persistent challenges. Treating these people with cisplatin and 5-FU intravenously would never be justified since the disease is rarely fatal, but this new technique spares off-target healthy tissue, providing effective, local and less invasive treatment for people with skin cancer.”
Since both cisplatin and 5-FU are already approved medications that have been commercially available for decades, the path to clinical implementation of the treatment is actually very short. However, the researchers believe that the techniques’ potential goes far beyond treating skin cancer.
“In clinics across the globe, laser-assisted drug delivery is experimentally used for a broad range of indications, including delivering topical anaesthetics instead of by needle injection, as well as treatment of premalignant skin lesions, scars and vitiligo and for delivering aesthetic agents such as platelet-rich plasma, Botox® and vitamins. The technique is clearly quite versatile, and we are excited to play a part in continuing to refine it.”
“Laser-assisted delivery enhances topical uptake of the anticancer agent cisplatin” has been published in Drug Delivery. In 2013, the Novo Nordisk Foundation awarded a grant to a main author, Merete Hædersdal, Clinical Professor, Department of Clinical Medicine, University of Copenhagen for the project New Targeted Treatment of Skin Cancer using Topical Administration of Anticancer Drugs in Combination with Laser-assisted Drug Delivery.