Biodegradable Porous Microneedle for Electric Skin Patch
Authors: Matsui Yuya , Kusama Shinya , Kimura Natsumi , Takizawa Ryohei , Yoshida Shotaro , Abe Yuina , Abe Hiroya , Nishizawa Matsuhiko 
Published: December 2020

Oral drugs administrate to a body with painless and low cost, however, the efficiency of most oral drugs is not high due to the metabolic degradation during adsorption process. In contrast, a skin patch-based transdermal drug delivery is attractive for avoiding the route of metabolic degradation, as well as its painless property. In order to improve the transdermal drug delivery, microneedle array has been of much interest since it can reach inside stratum corneum and enhance the transdermal adsorption of the drugs. Different types of microneedles of the drug-coated, the dissolvable, and the hollowed structure have been applied for skin patches. In the previous study, we have developed porous microneedles (PMN) consisting of glycidyl methacrylate (GMA) by using the porogen method with polyethylene glycol (PEG), which allowed fast water absorption and enough mechanical strength to reach into the skin [1]. Moreover, the GMA-PMN was proved to decrease the transdermal ionic resistance [2], and thus is expected to enhance the iontophoresis efficiency. However, since the tip of GMA-PMN remained in the body is hard to be metabolized, an adverse effect on the human body could be cased. In this study, we developed PMNs consisting of a biodegradable material, polylactic acid-glycolic acid copolymer (PLGA) (Figure 1A). In order to improve the hydrophilicity and mechanical strength of the PLGA-PMNs, the water-soluble and biodegradable polymer was composited to the PLGA-PMNs.

The PMN were fabricated by a combination of molding method and freeze-drying. PLGA dissolved in 1,4-dioxane was filled into a PDMS mold, frozen in a freezing chamber, and dried in a freeze-drying machine. The structure of the PMN chip consists of a substrate (8 mm in the width), the supporting posts (500 µm in diameter, 300 µm in height), and the needles (300 µm in length). The supporting post improves the penetration of the needle into the skin. The pitch between the centers of each needle is 1 mm. The pore size of the fabricated PMN was found to be about 10 µm from SEM images (Figure 1B). The mechanical strength evaluated by a force gauge and a load cell was 0.03 N/needle, which less than the enough strength to penetrate the skin (0.06 N/needle [3]). In order to improve the mechanical strength of the PLGA-PMNs, an aqueous solution of carboxymethyl cellulose (CMC) was filled in the pores of the PLGA-PMNs and dried. The CMC-filled PLGA-PMN showed a higher load-bearing capacity than the PLGA-PMN.

By soaking the PMN with saline solution and applying current, the ionic conduction through the PLGA-PMN chip was observed. In addition, the water adsorbing rate of the CMC-filled PLGA-PMN was faster than that of PLGA-PMN. These results indicate the pores of the PMN form continuous channels through the chip, and the CMC improves wettability of the PLGA-PMN due to its high hydrophilicity. In conclusion, we successfully fabricated porous microneedle from biodegradable materials and improved the mechanical strength and hydrophilicity by stuffing the biodegradable polymer, which provides a key role for practical applications.

References

[1] L. Liu, H. Kai, K. Nagamine, Y. Ogawa, M. Nishizawa, “Porous Polymer Microneedles with Interconnecting microchannels for rapid fluid transport.” RSC Advances 6, 48630-48635, (2016).

[2] K. Nagamine, J. Kubota, H. Kai, Y. Ono, M. Nishizawa, “An array of porous microneedles for trans dermal monitoring of intercellular swelling”, Biomed Microdevices, 19, 68, (2017)

[3] J.D. Kim, M. Kim, H. Yang, K. Lee, H. Jung, “Droplet-born air blowing: novel dissolving microneedle fabrication.” Control Release, 170(3), 430-436, (2013)

Figure 1