Recent Patents on Permeation Enhancers for Drug Delivery Through Nails

Abstract

: The human nail is a unique barrier with a keratinized constitution that favors protection and fine touch. However, many disorders can affect the nail, among them, are the onychomycosis and psoriasis. Systemic oral therapy has been applied to treat these diseases, even presenting disadvantages, including side effects, drug interactions, contraindications, toxicity, high cost and low patient compliance. A great option to succeed in dealing with the problems associated with oral therapy is the topical administration of drugs. However, nail composition, low diffusion through ungual route and reduced tissue bioavailability for topical treatments are limiting factors. These drawbacks can be overcome by promoting penetration through the nails by employing penetration enhancers. The review focuses on patents that highlight permeation enhancers applied to nail drug delivery for the treatment of onychomycosis and psoriasis. Literature and patent searches were conduced regarding the topic of interest. The substantial literature and patent search revealed that permeation enhancers, especially chemicals, are great strategies for promoting the ungual delivery of drugs. Nail topical therapy containing permeation enhancers is an attractive option for delivering localized treatments.

Onychomycosis: a review

“…Physical permeation enhancing methods includes etching, lasers, electropulsation, ultrasound, microneedling, hydration and iontophoresis, which either increase the surface area of application, introduce holes for deeper penetration or separate the keratin strands of the nail plate allowing larger molecules to penetrate. 163 An example of etching or microneedling is illustrated by a recent US patent that describes a nail treatment kit that etches 1 mm sized holes in the nail while dispensing antifungal treatment. 164 Iontophoresis, on the other hand, employs a small amount of electric current to enhance the delivery of the topical drug to the infected site.…”

“…165 Chemical permeation enhancers include solvents, enzymes, etchants and keratolytic agents, which either hydrate the nail and/or break the bonds between the nail keratin strands, both resulting in larger pores or spaces for topical treatment to pass through. 163 Two recently patented topical formulations employ vastly different penetration enhancing and antifungal characteristics. The WO2019088055A1 patent describes a formulation containing a classic antifungal drug, such as efinaconazole or luliconazole, alongside the penetration enhancer ethyl lactate, among other volatile and non-volatile chemicals.…”

“…Mechanical abrasion of the dorsal nail plate can increase the surface area of topical application by creating micro‐holes and ‐valleys in the surface of the nail. Physical permeation enhancing methods includes etching, lasers, electropulsation, ultrasound, microneedling, hydration and iontophoresis, which either increase the surface area of application, introduce holes for deeper penetration or separate the keratin strands of the nail plate allowing larger molecules to penetrate 163 . An example of etching or microneedling is illustrated by a recent US patent that describes a nail treatment kit that etches 1 mm sized holes in the nail while dispensing antifungal treatment 164 .…”

International Patent Survey of Products and Processes Concerning Homeopathy

“…by authors in other topics. [12][13][14] In the present study, 174 homeopathy-related patents were found for the period analyzed. In an original way, the patents were analyzed by nationality and type of applicants.…”

Prospective Nanotechnology-Based Strategies for Enhanced Intra- and Transdermal Delivery of Antifungal Drugs

“…Enhancement of antimycotic delivery using various solvents (dimethyl sulfoxide, methanol), enzymes, hydrogen peroxides, etc. were demonstrated for onychomycosis treatment as well [79, 80].…”