Enhanced Transdermal Delivery by Combined Application of Dissolving Microneedle Patch on Serum-Treated Skin

Abstract

Dissolving microneedle (DMN), a transdermal drug delivery system in which drugs are encapsulated in a biodegradable polymeric microstructure, is designed to dissolve after skin penetration and release the encapsulated drugs into the body. However, because of limited loading capacity of drugs within microsized structures, only a small dosage can be delivered, which is often insufficient for patients. We propose a novel DMN application that combines topical and DMN application simultaneously to improve skin permeation efficiency. Drugs in pretreated topical formulation and encapsulated drugs in DMN patch are delivered into the skin through microchannels created by DMN application, thus greatly increasing the delivered dose. We used 4-n-butylresorcinol to treat human hyperpigmentation and found that sequential application of serum formulation and DMNs was successful. In skin distribution experiments using Alexa Fluor 488 and 568 dyes as model drugs, we confirmed that the pretreated serum formulation was delivered into the skin through microchannels created by the DMNs. In vitro skin permeation and retention experiments confirmed that this novel combined application delivered more 4-n-butylresorcinol into the skin than traditional DMN-only and serum-only applications. Moreover, this combined application showed a higher efficacy in reducing patients' melanin index and hyperpigmented regions compared with the serum-only application. As combined application of DMNs on serum-treated skin can overcome both dose limitations and safety concerns, this novel approach can advance developments in transdermal drug delivery.

Skin Barrier Restoration and Moisturization Using Horse Oil-Loaded Dissolving Microneedle Patches

“…1b). According to previous studies about skin penetration using DMN, a tip diameter of HO-DMN is suitable to penetrate the epidermal layer [10, 31]. The fracture force of a single HO-DMN was 0.29 ± 0.01 N (Fig.…”

“…Such formulations, however, make it difficult for the active compounds in HO to be delivered to the target site in the epidermis, because the stratum corneum, the outermost skin layer, acts as a barrier, blocking the entrance of external substances [9, 10]. This limited permeation is one of the major obstacles to maximizing the efficacy of active compounds for cosmetic applications.…”

Combinatorial application of dissolving microneedle patch and cream for improvement of skin wrinkles, dermal density, elasticity, and hydration

“…The present study described the combinatorial application of traditional DMN patches and cream formulation for the delivery of greater quantities of encapsulated drugs into dermal layer and thus enhancing the efficacy in humans. Traditional combination methods, in which the cream is applied first, have many limitations, such as time constraints and delivery efficiency owing to the pre‐treated serum formulation . As the ingredients of the topical formulations can vary, the optimal interval could be affected by the drying rate and thus it is difficult to meet the optimal interval for users.…”

“…A combination of DMN patches and serum was applied to overcome DMN dose limitations via the delivery of a skin‐depigmenting agent in topical serum and sequential patch application . As the liquid formulation of topical serum dissolved the biodegradable DMNs before penetration into the skin, the optimal interval to prevent DMN dissolution was investigated for effective drug delivery.…”

Two‐phase delivery using a horse oil and adenosine‐loaded dissolving microneedle patch for skin barrier restoration, moisturization, and wrinkle improvement

“…Recently, DMN patches combined with topical serum have been developed to overcome the loading limitation and enhance the aesthetic effects . The hydrophilic active compound, 4‐n‐butylresorcinol, was formulated in both topical serum and DMNs, and DMN patches were applied after serum treatment.…”