Development of Botulinum Toxin A-Coated Microneedles for Treating Palmar Hyperhidrosis

Abstract

Hyperhidrosis is a disorder that is characterized by the production of excess amounts of sweat. The botulinum neurotoxin A (BoNT/A) has been used to treat hyperhidrosis through multiple intradermal injections at the site of the condition. However, because of BoNT/A toxicity, it is important to precisely deliver the proper dose of the toxin to the target site. In addition, the use of a conventional hypodermic needle for multiple injections in the palm makes the approach undesirable and painful. Here, we designed a BoNT/A-coated microneedle (BoNT-MN) array and tested its efficacy as a substitute pain-free method to treat hyperhidrosis. BoNT-MNs were prepared by coating polylactic acid microneedles with a BoNT/A formulation and were found to successfully penetrate into a thick skin in vitro. The coating formulations were then tested for their stability at 4, 25, and 37 °C for 24 h. BoNT-MNs were found to be much more stable than BoNT/A in a liquid state. Additionally, we carried out in vivo experiments by treating the right paws of mice with BoNT-MNs and found that the treatment induced a significant reduction in the sweating response in the mouse foot pad. Thus, BoNT/A treatment using microneedles is beneficial and may be used as a more efficient and less painful approach to treat hyperhidrosis.

Botulinum Toxins in Medical and Cosmetic Dermatology

“…26 An in vivo murine study demonstrated that BoNT-A-coated polylactic acid microneedles are a safe and effective delivery method, resulting in significantly decreased sweating. 27 Delivery of BoNT-A using a combined fractional ablative laser and ultrasound has been trialled successfully to treat palmar hyperhidrosis. 28 A topical formulation of BoNT-A in a liposomal base applied nightly for 7 nights was found to be effective at reducing axillary sweat for up to 8 weeks, compared to vehicle alone, suggesting that painless delivery methods for BoNT are on the horizon.…”

Enhancement strategies for transdermal drug delivery systems: current trends and applications

“…[ 230 ] for delivery of desmopressin. Subsequently, this type of MN has been used for enhancing the delivery of other macromolecules, such as insulin [ 254 ], deoxyribonucleic acid (DNA) [ 255 ], exendin-4 [ 256 ], botulinum toxin-A [ 257 ] and peptide-A [ 258 ]. Furthermore, the use of coated MN has also been reported for delivery of lidocaine [ 259 ] and riboflavin [ 260 ].…”

“…16 Coated MN with different drug coatings: (a) Desmopressin (reproduced with permission from [230] Copyright 2004, Elsevier). (b) DNA (reprinted with permission from [255] Copyright © 2010, American Chemical Society) used for enhancing the delivery of other macromolecules, such as insulin [254], deoxyribonucleic acid (DNA) [255], exendin-4 [256], botulinum toxin-A [257] and peptide-A [258]. Furthermore, the use of coated MN has also been reported for delivery of lidocaine [259] and riboflavin [260].…”

A Practical Approach to the Diagnosis and Treatment of Palmar Hyperhidrosis

“…BoNTA-coated microneedles: The use of microneedles coated with BoNTA is a novel and exciting procedure that may lead to positive results in treating PH. 55 A study published by Shim et al in 2019 outlined a design for BoNTA-coated microneedles, and tested its use in the foot pad of mice in vivo, showing a significant reduction in the sweating response. 55 While this method is a promising, and potentially less painful approach to treating PH, additional research is necessary to confirm its efficacy in humans.…”