Dissolving microneedles (DMNs) are polymeric, microscopic needles that deliver encapsulated drugs in a minimally invasive manner. Currently, DMN arrays are superimposed onto patches that facilitate their insertion into skin. However, due to wide variations in skin elasticity and the amount of hair on the skin, the arrays fabricated on the patch are often not completely inserted and large amount of loaded materials are not delivered. Here, we report “Microlancer”, a novel micropillar based system by which patients can self-administer DMNs and which would also be capable of achieving 97 ± 2% delivery efficiency of the loaded drugs regardless of skin type or the amount of hair on the skin in less than a second.

COMMUNICATION (1 of 7)© 2017 WILEY-VCH Verlag GmbH & Co. KGaA Polymeric microstructures containing biological materials have attracted attention for various biomedical applications, such as scaffolds for cell proliferation and drug-eluting reservoirs for controlled release. [1][2][3][4][5][6] Recently, dissolving microneedles (DMNs), which are implantable microscale-polymeric needles that release biopharmaceutics from their dissolving polymer matrix into the skin, have been investigated as an alternative biomedical delivery system to hypodermic injection owing to their minimal invasiveness and reduced side effects compared with traditional hypodermic injection. [7][8][9] Therefore, selfadministrable DMNs are applied to deliver biopharmaceutics, Polymeric microstructures encapsulating biopharmaceutics must be fabricated in a controlled environment to preserve the biological activity. There is increasing demand for simple methods designed to preserve the biological activity by utilizing the natural properties of polymers. Here, the paper shows that centrifugal lithography (CL) can be used for the fabrication of such microstructures in a single centrifugation, by engineering the self-shaping properties of hyaluronic acid (HA). In this method, HA drops are self-shaped into hourglass-microstructures to produce two dissolving microneedles (DMN), which facilitate transdermal delivery via implantation on the skin. In addition, tuberculin purified protein derivatives are encapsulated into HA DMNs under refrigerated conditions (4 °C) during CL. Therefore, the tuberculin skin test (TST) with the DMNs indicates minimal damage, as opposed to the case of TST with traditional hypodermic needles. These findings on the fabrication of polymeric microstructures with biopharmaceutics may trigger the development of various biomedical devices and therapies.

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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.

The dissolving microneedle (DMN) patch is a transdermal delivery system, containing arrays of micro-sized polymeric needles capable of encapsulating therapeutic drugs within their matrix and releasing them into the skin. However, the elastic properties of the skin prevent DMNs from complete insertion and accurate delivery of encapsulated compounds into the skin. Moreover, the adhesive materials used in patches may cause skin irritation, inflammation, and redness. Therefore, we developed a patchless, micro-pillar integrated DMN (P-DMN) that is simple to fabricate and enhances transdermal drug delivery compared with traditional DMN patches. The micro-pillars were made of polymethyl methacrylate at a height of 300 μm and a base diameter of 500 μm. To fabricate P-DMNs, we employed hyaluronic acid, which is a widely used derma filler and plays a role in tissue re-epithelialization. We demonstrate that utilizing P-DMNs significantly improves the delivery efficiency of an encapsulated drug surrogate (91.83% ± 7.75%) compared with traditional DMNs (64.86% ± 8.17%). Interestingly, P-DMNs remarkably increase the skin penetration accuracy rate of encapsulated drugs, up to 97.78% ± 2.22%, compared with 44.44% ± 7.85% in traditional DMNs. Our findings suggest that P-DMNs could serve as a highly accurate and efficient platform for transdermal delivery of various types of micro- and macro-biomolecules.