Topical Botulinum Toxin: An Update

Approximately five years ago, there was much buzz about the possibility of a topical neurotoxin. The advantages were obvious: Needle-phobic patients would have an option, and, perhaps, it could have the same lasting effects as injectable neurotoxin without pain or discomfort.

So where are we now in the development of this new neurotoxin modality?

I recently ran into a pharmaceutical company representative who offered this simple answer: “Topical Botox—they tried, but it never worked.”

An Unmet Need?

The disadvantages of an injectable neurotoxin include more than just pain, which affects a significant patient population, including children who receive the injectables for cerebral palsy and neuromuscular disorders. The possibility of switching to a topical from an injectable may also save on costs, as injectables require additional preparation of mixing the product with saline, using ultra-fine insulin syringes, topical lidocaine, gauze, cotton-tipped applicators, sharps containers, and other devices needed close by when administering an injection.

In initial phases, newer methods of a topical botulinum toxin formulation showed evidence of bioactivity in small clinical studies.¹ While there are risks associated with both treatments, risks of topical delivery appeared to be less than those with injectable therapies. Refining the delivery of a topical botulinum toxin using nanotechnology is widely anticipated and standardizing techniques and delivery systems is a goal for the near future.²

Initial evaluation showed that topical botulinum toxin is highly resistant to absorption transdermally. In the treatment of axillary hyperhidrosis, a topical botulinum toxin cream was evaluated as a new, noninvasive modality to enhance skin penetration.³ A clinical study of axillary hyperhidrosis found that a topical liposomal botulinum toxin A cream enhances drug delivery and is cost-effective, painless, and innovative. Results showed decreased sweating and improved patient satisfaction after several weeks of treatment of axillary skin without adverse effects.³

Hyperhidrosis of the palms, axillae, and plantar feet is a common, burdensome, occupationally bothersome, and possibly even a hazardous condition to deal with. Treatment modalities are cumbersome and difficult to get a hold of, ranging from topical antiperspirants to systemic therapies such as anticholinergics, as well as more invasive interventions such as botulinum toxin injections and thoracic sympathectomies. While intradermal injections of botulinum toxin are effective, they are difficult to gain insurance approval for, and painful, as many injections are required over the surface area being targeted. Iontophoretic administration of Botox has been described as the toxin would enter eccrine sweat glands via sweat ducts and sweat pores.⁴ While the rationale seems promising, the feasibility of the topical treatment of botulinum toxin assisted through the application of an electrical gradient and low-frequency ultrasound needs further exploration.⁴

A study published by the American Society of Dermatologic Surgery evaluated the use of a topical botulinum toxin type A gel for the treatment of lateral canthal lines.⁵ It appears to avoid a host of complications that accompany injections, including bruising, potential infection, redness/erythema, and pain. At the study’s conclusion, it was found to demonstrate improvement of lateral canthal lines and was found to be well-tolerated in patients, with no treatment-related adverse effects reported.⁵

Topical Alternatives

There are also alternatives investigated compared to Botox, including acetyl hexapeptide-8, which can be applied topically as a cream or serve as an injectable therapy.⁶ Argireline has less toxic potential than Botox. It has been studied in mice as an oil-and-water emulsion twice daily and was found to stimulate genesis of collagen type III when applied twice daily for six weeks. A total of 10% Argireline applied twice daily to 24 women 30 to 60 years of age for 60 days showed a decrease in trans-epidermal water loss compared to placebo, which caused a significant increase in the moisturization of the stratum corneum.⁴ Acetyl hexapeptide-8 may serve as a possible alternative for Botox because it can be used as a topical agent and has been found to have anti-aging properties. It also appears to have improved safety compared to Botox.⁶

Several studies have examined other topical products that claim to achieve similar or better outcomes than botulinum toxin type A in the treatment of wrinkles. However, no clinical data or objective measures have been found to support these claims.⁷

Despite the current economic struggles as a result of the pandemic, there continues to be an increasing demand for minimally invasive cosmetic treatments to slow the aging process. Injections of botulinum toxin continue to be the most common nonsurgical aesthetic procedure performed. Offering a different benefit, Revance Therapeutics has been working steadily on developing a neurotoxin product, Daxibotulinumtoxin A, with a six-month vs. three to four months lasting effect.⁸

Although research and clinical studies have probed into a possible topical botulinum toxin, there has not been FDA approval of such a product at this time, and a longer-lasting neurotoxin appears to be more feasible and nearer in the pipeline compared to a topical product.

References:

1. Collins A, Nasir A. Topical botulinum toxin. J Clin Aesthet Dermatol. 2010;3(3):35-39.
2. Saffarian P, Fooladi AAI. Topical Botulinum Toxin: A Non-invasive Way for Treatment of Muscle Disorders. Curr Drug Deliv. 2018;15(10):1375-1380.
3. Lueangarun S, Sermsilp C, Tempark T. Topical Botulinum Toxin Type A Liposomal Cream for Primary Axillary Hyperhidrosis: A Double-Blind, Randomized, Split-Site, Vehicle-Controlled Study. Dermatol Surg. 2018 Aug;44(8):1094-1101.
4. Lim EC, Seet RC, Chow A, Oh VM, Ong BK, Wilder-Smith EP. Topical botulinum toxin to treat hyperhidrosis? No sweat! Med Hypotheses. 2006;67(1):27-32.
5. Brandt F, O'Connell C, Cazzaniga A, Waugh JM. Efficacy and safety evaluation of a novel botulinum toxin topical gel for the treatment of moderate to severe lateral canthal lines. Dermatol Surg. 2010 Dec;36 Suppl 4:2111-8.
6. Satriyasa BK. Botulinum toxin (Botox) A for reducing the appearance of facial wrinkles: a literature review of clinical use and pharmacological aspect. Clin Cosmet Investig Dermatol. 2019;12:223-228.
7. Beer KR. Comparative evaluation of the safety and efficacy of botulinum toxin type A and topical creams for treating moderate-to-severe glabellar rhytids. Dermatol Surg. 2006 Feb;32(2):184-197.
8. Carruthers J, Solish N, Humphrey S, Rosen N, Muhn C, Bertucci V, Swift A, Metelitsa A, Rubio RG, Waugh J, Quiring J, Shears G, Carruthers A. Injectable DaxibotulinumtoxinA for the Treatment of Glabellar Lines: A Phase 2, Randomized, Dose-Ranging, Double-Blind, Multicenter Comparison With OnabotulinumtoxinA and Placebo. Dermatol Surg. 2017 Nov;43(11):1321-1331.