Innovations in Transdermal Drug Delivery

Current innovations in transdermal drug delivery are capable of delivering macro-hydrophilic molecules, including therapeutic proteins and vaccines, across the stratum corneum. Read which companies and universities Frost & Sullivan believes will have a significant impact on the administration of medications.

In 1979, the first transdermal system for systemic delivery approved in the United States was a scopolamine patch to treat motion sickness. The first generation of transdermal delivery systems was mostly aimed at delivering drugs having low molecular weight and lipophilic properties, and showed good efficacy at low doses. This was followed by approval of nicotine, anesthetic and hormone patches. The drugs would be dissolved in a liquid or gel-based reservoir and delivered in a gel, spray or topical formulation or incorporated in a patch with an adhesive layer.

Current innovations, such as thermal ablation, dissolving microneedles and novel approaches to well-known iontophoresis, are capable of delivering macro-hydrophilic molecules, including therapeutic proteins and vaccines, across the stratum corneum. Some of these are still in early stages of development. Frost & Sullivan believes the following companies and universities will have a significant impact on the administration of medications.

Skin Ablation

Thermal ablation is a non-invasive technique to remove small portions of the stratum corneum and increase skin permeability through micron-scale channels into the skin. Ablation can be done through various methods using ultrasound, near-infrared (NIR) light and lasers.

LaserLeap Technologies, headquartered in Coimbra, Portugal, has created a device that converts laser energy into photoacoustic, or pressure, waves. With just two minutes of applied pressure waves, an increase in transepidermal water loss provides entry points for larger molecular transport of topical analgesics, insulin, biologics, vaccines or DNA-based pharmaceuticals. The skin regains its protective ability within minutes of treatment.

If a light saber to the face sounds like a deterrent, researchers at Kumamoto University in Japan have developed a novel transdermal thermal ablation system using the concept of photothermic ablation. This delivery system consists of gold nanorods, fluorescently labeled ovalbumin (egg-white protein), transparent gel patches and NIR light. When exposed to NIR light, the gold nanorods increase skin temperature to about 45 degrees Celsius, resulting in significant translocation of the fluorescently labeled ovalbumin on murine skin. The results confirm the system’s ability to perforate the stratum corneum and facilitate the passage of proteins across the skin. The researchers have yet to use this new method for actual therapeutic purposes, but it shows promise.

Using their own NIR technology, scientists at Beijing Key Laboratory for Bioengineering and Sensing Technology are testing the use of NIR irradiation on hyaluronic acid-encapsulated copper sulfide gel as a means of transdermal insulin delivery. The gel showed great biocompatibility and photothermal translation efficacy when irradiated. The technology showed sustained and efficient transdermal insulin delivery in nude mice, decreasing blood glucose level. Additional laboratory testing is required before moving on to human trials, but the technology continues to show promise for eliminating the need for insulin injections.

Electrical Technologies

Iontophoresis is a well-known method to deliver medicine or other chemicals through the skin using low-density electric currents (less than 0.5 milliamperes per square centimeter). Electricity is applied from a few minutes to several hours. The mild electric current creates a potential difference across the skin membrane, facilitating the transfer of ions.  

The Medicines Company of Parsippany, N.J., developed a U.S. Food and Drug Administration-approved method to deliver fentanyl transdermally for the short-term management of acute post-operative pain in adult patients. IONSYS is a credit card-sized device that adheres to the skin and uses imperceptible electric current for on-demand, controlled fentanyl delivery. To activate the device, the patient must press the dosing button twice within three seconds; a flashing green light acknowledges active delivery. Because of the high risk of opioid addiction, fentanyl administration can only be activated every 10 minutes.

On days when having to activate an opioid patch seems daunting, Gilroy, Calif.-based ActivaTek has your back—or any other area on which you want to apply its intelligent iontophoresis ActivaPatch. The company’s self-proclaimed premier product in the ActivaPatch line, the IntelliDose 2.5, is a self-powered, microprocessor-controlled, flexible iontophoresis patch. The ActivaPatch can deliver a 40 or 80 milliampere-minute treatment in approximately 2.5 hours. This device requires no separate dose controllers, charging stations or battery packs. Its patented SHUNT technology automatically turns off the ActivaPatch once the treatment is complete. An intelligent biofeedback microprocessor and SmartPower LED allows each patch to communicate with both clinician and patient, ensuring effective drug delivery by accurately measuring skin impedance and operational effectiveness.

Mechanical Methods

Microneedle arrays are micrometer-sized needles that help create superficial pathways across the skin to allow for the delivery of macromolecules, nanoparticles or other pharmaceuticals to the target. The microneedles’ sharp tips are short enough to limit contact with skin nerves (thus preventing pain sensation) and are narrow enough to induce minimal trauma. This method combines the efficacy of conventional injection needles with the convenience of transdermal patches.

The commonly available microneedles are made of silicon, metal or ceramic. Polymeric microneedles have excellent biocompatibility, biodegradability and nontoxicity. They are easy to fabricate in large scale and can load drugs in high amounts. Polymers with different degradation profiles, swelling properties and responses to biological/physical stimuli can be used to fabricate polymeric microneedles.

Micron Biomedical of Atlanta produces a “peel and stick” microneedle patch for the delivery of medicine and vaccines using an exclusive formulation and manufacturing technology to encapsulate the active ingredients and provide thermostability. These patches painlessly penetrate the upper layers of skin and then dissolve rapidly to release the medicine or vaccine. After a few minutes, the patch can be removed and disposed of without the need for a sharps waste container. Micron believes its painless patch can significantly increase the number of people getting vaccinated.

The Road Ahead

The transdermal drug delivery industry has taken tremendous strides over the past few years, and researchers continue to develop more convenient devices for a broader range of therapeutic indications. Technological innovations are addressing the molecule size limitations of traditional transdermal systems.

Frost & Sullivan believes advances in microneedles and other transdermal technologies will expand treatment availability to include patch solutions for diabetes, hormonal imbalances, neurological conditions and cancer.

Copyright © 2018 Frost & Sullivan