One of the most convenient and safest ways to deliver medicine into the body is via the topical route, through the skin into the dermis where the drug can be absorbed into the body or take effect locally. This route of administration ensures a steady release of the drug and avoids the issue of hepatic first-pass metabolism encountered with the traditional orally administered medications.
Introducing medicines into the body this way is traditionally done by parenteral administration using a needle and syringe to inject drugs into the skin and deeper structures but as we know, this can be painful and sometimes feared by the patient. The second means is via a topical vehicle such as a cream, ointment or lotion. Although preferred by patients to injections, drugs delivered via this route have to be able to cross the epidermis in effective quantities to have any therapeutic effect. This is often compounded by patients with hyperkeratotic disorders where there is abnormal thickening of the epidermis hampering effective drug delivery.
To overcome the issues of traditional drug delivery through the skin, we have seen the emergence of microneedles, particularly of interest are the dissolving variety (DMN). The concept is simple - manufactured from biodegradable polymers or soluble products, they can be incorporated into a flexible dressing and combined with the desired drug to make a unique delivery system. The microneedles are able to pierce the skin and make multiple micro channels through which drugs can be delivered into the skin before the DMN themselves are degraded. Microneedles do not lead to stimulation of cutaneous nerve endings and so are generally considered painless. Depending on their length they can be intra-epidermal or dermal and are able to deliver both small and large molecules of medicine into the desired section of the skin. So what can they be used for? Recent applications have included drug delivery in oncology and diabetes. A recent systematic review [1] has looked at studies to date exploring this potentially groundbreaking system.
Microneedles are a new way to deliver drugs into the skin. (Image: Physicsworld.com)
The authors undertook a systematic review of all randomised controlled trials which included the use of DMN’s. A total of 17 trials were included in the final analysis, meeting the stringent review criteria of original, high quality research with limited risk of bias. The pooled results showed most trials were conducted in aesthetics settings, on the face of women using hyaluronic acid as an aesthetic agent. For most studies advantages were seen in the aesthetic results using this drug delivery method.
Close up of the dissolving microneedles
Medical uses of the microneedles were studied in 3 trials. The first looked at topical steroid delivery in patients with nail psoriasis (using a topical application v DMN). The work concluded microneedle delivery was more sustained and had an overall improvement in clinical scores using the NAPSI scoring system. The second study was a clinical trial in 42 patients with multiple warts. Cryotherapy was compared against DMN delivery of bleomycin. Although the outcome of the two modalities were similar, the DMN group with bleomycin reported much less pain. A third study demonstrated that DMN infusion of steroid and hyaluronic acid into keloids (versus placebo) showed significant reduction in keloid volume along with a good safety profile.
So what applications might this technology have in dermatology? It is in its early stages, but one can envisage potential applications, particularly for drug delivery into hyperkeratotic skin where topical ointments may have failed. Safe and metered dosed introduction of steroids into inflammatory skin lesions is an appealing prospect with little need for patient intervention and potentially sustained effects. Moreover, the treatment of warts may benefit from this as a means of penetrating hyperkeratotic lesions with antivirals. Effective surface anaesthesia seems unexplored at this stage but may have future clinical applications along with antimicrobial agents. New developments are occurring at a pace with DMN’s delivering a range of drugs including ciclosporin, methotrexate and diclofenac as the authors suggest in the review paper.
Reference
1. De Decker, I., et al., Dissolving microneedles for effective and painless intradermal drug delivery in various skin conditions: A systematic review. The Journal of Dermatology, 2023. Early view.