Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, No. 29, Zhongguancun East Road, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19, Yuquan Road, Beijing 100049, China.
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, No. 29, Zhongguancun East Road, Beijing 100190, China; Beijing CAS Microneedle Technology Ltd, No. 22, Tianrong Street, Beijing 102609, China.
Int J Pharm. 2022 Apr 25;618:121669. doi: 10.1016/j.ijpharm.2022.121669. Epub 2022 Mar 16.
We describe a swellable microneedle (SMN) consisting of Ca cross-linked alginate, which expands the types of natural polymers available for SMN fabrication. After investigation of different fabrication methods, the alginate in situ hydrogel-based SMN with a flat substrate was successfully constructed, whose gelation was triggered by ethylenediaminetetraacetic acid calcium disodium salt and D-(+)-glucono-1,5-lactone. With the addition of polyvinyl alcohol and trehalose, SMN possessed good mechanical properties. The biocompatibility of SMN was demonstrated through the tests of in vitro cytotoxicity and in vivo skin irritation. With the assistance of SMN, the in vitro transdermal delivery efficiencies of drugs were significantly improved throughout 16 h. 3-O-ethyl ascorbic acid (EAA, pH = 4.81) exhibited a cumulative release of up to 83.83 ± 6.30%, which was consistent with zero-order kinetics, while tranexamic acid (TA, pH = 6.90) showed the most significant increase in delivery efficiency, which was consistent with the Higuchi model and Ritger-Peppas model. The SMN remained intact after the 16 h of EAA transdermal delivery, indicating its better suitability for acidic drugs. We believe that this technology has the potential to expand the range of drugs available for transdermal administration as well as the breadth of patient care applications.
我们描述了一种可溶胀的微针（SMN），它由交联的海藻酸钠组成，这扩展了可用于 SMN 制造的天然聚合物的类型。在研究了不同的制造方法后，成功构建了具有平坦基底的基于海藻酸钠原位水凝胶的 SMN，其凝胶化是由乙二胺四乙酸二钙二钠盐和 D-（+）-葡萄糖-1,5-内脂触发的。通过添加聚乙烯醇和海藻糖，SMN 具有良好的机械性能。通过体外细胞毒性和体内皮肤刺激性试验证明了 SMN 的生物相容性。在 SMN 的辅助下，药物的体外透皮递送效率在 16 小时内得到了显著提高。3-O-乙基抗坏血酸（EAA，pH=4.81）的累积释放量高达 83.83±6.30%，符合零级动力学，而氨甲环酸（TA，pH=6.90）的递送效率显著提高，符合 Higuchi 模型和 Ritger-Peppas 模型。在进行 16 小时 EAA 透皮递送后，SMN 仍保持完整，表明其更适合于酸性药物。我们相信，这项技术有可能扩大可用于透皮给药的药物范围，并拓宽患者护理应用的广度。
