Luan Xi, Zhang Xiaoxuan, Nie Min, Zhao Yuanjin
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Pharmacy, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Research (Wash D C). 2023 May 9;6:0141. doi: 10.34133/research.0141. eCollection 2023.
Traditional Chinese medicine, such as and , has potential values in treating systemic sclerosis (SSc) and other autoimmune diseases, while their toxic side effect elimination and precise tropical drug delivery are still challenges. Here, we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus (BP) microneedles (MNs) with the desired features for the SSc treatment. By employing a template-assisted layer-by-layer curing method, such MNs with triptolide (TP)/paeoniflorin (Pae) needle tips and BP-hydrogel needle bottoms could be well generated. The combined administration of TP and Pae can not only provide anti-inflammatory, detoxification, and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery. Besides, the additive BPs possess good biocompatibility and near-infrared (NIR) responsiveness, imparting the MN photothermal-controlled drug release capability. Based on these features, we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia, reduce collagen deposition, and reduce epidermal thickness in the SSc mouse models. These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.
诸如雷公藤和芍药苷等传统中药在治疗系统性硬化症（SSc）和其他自身免疫性疾病方面具有潜在价值，但其毒副作用消除和精确的经皮给药仍是挑战。在此，我们展示了多种整合了传统中药的光响应性黑磷（BP）微针（MNs），其具有治疗SSc所需的特性。通过采用模板辅助逐层固化方法，可以很好地制备出具有雷公藤内酯醇（TP）/芍药苷（Pae）针尖和BP水凝胶针底的此类微针。TP和Pae联合给药不仅可以提供抗炎、解毒和免疫调节作用以治疗SSc早期的皮肤病变，还能显著降低单一药物递送的毒性。此外，添加的黑磷具有良好的生物相容性和近红外（NIR）响应性，赋予了微针光热控释药物的能力。基于这些特性，我们已证明整合了传统中药的响应性微针可以有效改善SSc小鼠模型中的皮肤纤维化和毛细血管扩张，减少胶原蛋白沉积，并减小表皮厚度。这些结果表明，所提出的整合了中药的响应性微针在SSc及其他疾病的临床治疗中具有巨大潜力。
