Naito Chihiro, Katsumi Hidemasa, Suzuki Tomoko, Quan Ying-Shu, Kamiyama Fumio, Sakane Toshiyasu, Yamamoto Akira
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan.
CosMED Pharmaceutical Co., Ltd., Minami-ku, Kyoto 601-8014, Japan.
Pharmaceutics. 2018 Nov 4;10(4):215. doi: 10.3390/pharmaceutics10040215.
Human parathyroid hormone (1-34) (PTH) has been widely used as the subcutaneous injection formulation for the treatment of osteoporosis. In the present study, we developed an efficient transdermal delivery system of PTH by using dissolving microneedle arrays (MNs) composed of hyaluronic acid (HA) for the treatment of osteoporosis. PTH-loaded MNs, with needle length 800 µm, were fabricated via a micro-molding method. The stability of PTH in MNs was found to be 6-fold higher than that of PTH solution when stored at room temperature (15⁻20 °C) for one month. Micron-scale pores were clearly visible in rat skin following application of PTH-loaded MNs. PTH-loaded MNs were completely dissolved by 60 min following application to rat skin. The bioavailability (BA) of PTH relative to subcutaneous injection was 100 ± 4% following application of PTH-loaded MNs in rats. In addition, PTH-loaded MNs were found to effectively suppress decreases in bone density in a rat model of osteoporosis. Furthermore, no skin irritation was observed at the site of application in rats. These findings indicate that our dissolving MNs have a potential use in formulations for the transdermal delivery of PTH and for the treatment of osteoporosis.
人甲状旁腺激素（1-34）（PTH）已被广泛用作皮下注射制剂来治疗骨质疏松症。在本研究中，我们通过使用由透明质酸（HA）组成的溶解微针阵列（MNs）开发了一种高效的PTH经皮给药系统，用于治疗骨质疏松症。通过微成型方法制备了针长为800 µm的载PTH微针。当在室温（15-20°C）下储存一个月时，发现微针中PTH的稳定性比PTH溶液高6倍。在应用载PTH微针后，在大鼠皮肤中清晰可见微米级的孔。载PTH微针应用于大鼠皮肤后60分钟内完全溶解。在大鼠中应用载PTH微针后，PTH相对于皮下注射的生物利用度（BA）为100±4%。此外，发现载PTH微针可有效抑制骨质疏松症大鼠模型中的骨密度降低。此外，在大鼠的应用部位未观察到皮肤刺激。这些发现表明，我们的溶解微针在PTH经皮给药制剂和骨质疏松症治疗中具有潜在用途。
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