金丝桃素乳剂联合中空微针作为一种治疗类风湿关节炎的非侵入性光动力平台。
Hypericin emulsomes combined with hollow microneedles as a non-invasive photodynamic platform for rheumatoid arthritis treatment.
机构信息
Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
出版信息
Int J Pharm. 2024 Mar 25;653:123876. doi: 10.1016/j.ijpharm.2024.123876. Epub 2024 Feb 7.
Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease that severely affects joint function. Despite the variability of treatment protocols, all of them are associated with severe side effects that compromise patient compliance. The main aim of the current study is to prepare localized effective RA treatment with reduced side effects by combining nanoencapsulation, photodynamic therapy (PDT) and hollow microneedles (Ho-MNs) to maximize the pharmacological effects of hypericin (HYP). To attain this, HYP-loaded emulsomes (EMLs) were prepared, characterized and administered through intradermal injection using AdminPen™ Ho-MNs combined with PDT in rats with an adjuvant-induced RA model. The prepared EMLs had a spherical shape and particle size was about 93.46 nm with an absolute entrapment efficiency. Moreover, confocal imaging indicated the interesting capability of Ho-MNs to deposit the HYP EMLs to a depth reaching 1560 µm into the subcutaneous tissue. In vivo, study results demonstrated that the group treated with HYP EMLs through Ho-MNs combined with PDT had no significant differences in joint diameter, TNF-α, IL1, HO-1, NRF2 and SD levels compared with the negative control group. Similarly, rats treated with the combination of HYP EMLs, Ho-MNs and PDT showed superior joint healing efficacy compared with the groups treated with HYP EMLs in dark, HYP ointment or HYP in microneedles in histopathological examination. These findings highlight the promising potential of photoactivated HYP EMLs when combined with Ho-MNs technology for RA management. The presented therapeutic EMLs-MNs platform could serve as a powerful game-changer in the development of future localized RA treatments.
类风湿性关节炎(RA)是一种关节破坏性的自身免疫性疾病,严重影响关节功能。尽管治疗方案存在差异,但所有方案都与严重的副作用有关,这会影响患者的依从性。本研究的主要目的是通过结合纳米囊泡化、光动力疗法(PDT)和空心微针(Ho-MNs)来制备局部有效的 RA 治疗方法,以减少副作用,从而最大限度地发挥金丝桃素(HYP)的药理作用。为此,制备了载有 HYP 的乳剂(EMLs),并通过皮内注射使用 AdminPen™ Ho-MNs 联合 PDT 对佐剂诱导的 RA 模型大鼠进行给药,对其进行了表征。所制备的 EMLs 呈球形,粒径约为 93.46nm,绝对包封效率为。此外,共聚焦成像表明 Ho-MNs 具有将 HYP EMLs 沉积到皮下组织 1560µm 深处的有趣能力。体内研究结果表明,与阴性对照组相比,通过 Ho-MNs 联合 PDT 给予 HYP EMLs 的组在关节直径、TNF-α、IL1、HO-1、NRF2 和 SD 水平方面没有显著差异。同样,与在黑暗中给予 HYP EMLs、HYP 软膏或 HYP 微针的组相比,联合给予 HYP EMLs、Ho-MNs 和 PDT 的组在组织病理学检查中显示出更好的关节愈合效果。这些发现强调了光活化 HYP EMLs 与 Ho-MNs 技术联合用于 RA 管理的巨大潜力。所提出的治疗性 EMLs-MNs 平台可能成为未来局部 RA 治疗发展的强大变革者。