National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
Int J Pharm. 2023 Aug 25;643:123205. doi: 10.1016/j.ijpharm.2023.123205. Epub 2023 Jul 6.
Intraocular inflammation seriously impairs vision, and the effectiveness of intraocular drug delivery is hampered by various physiological barriers, such as the corneal barrier. In this paper, we present a simple approach to fabricating a dissolvable hybrid microneedles (MNs) patch for the efficient delivery of curcumin to treat intraocular inflammatory disorders. Water-insoluble curcumin was first encapsulated into polymeric micelles with high anti-inflammatory capacities, and then were combined with hyaluronic acid (HA) to create a dissolvable hybrid MNs patch using a simple micromolding method. Curcumin was amorphously dispersed within the MNs patch as indicated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses. According to an in vitro drug release study, the proposed MNs patch provided sustainable drug release over 8 h. Following its in vivo topical application, the MNs patch demonstrated an extended pre-corneal retention time over 3.5 h and exhibited great ocular biocompatibility. Additionally, such MNs patch could reversibly penetrate the corneal epithelium, generating an array of microchannels on the corneal surface, thereby increasing ocular bioavailability. Of greater significance, the use of MNs patch demonstrated the improved therapeutic effectiveness in treating endotoxin-induced uveitis (EIU) in a rabbit model compared to curcumin eye drops via a significant reduction in the infiltration of inflammatory cells such as CD45 leukocytes and CD68 macrophages. Overall, the topical application of the MNs patch as an efficient ocular drug delivery system could potentially serve as a promising approach for treating different types of intraocular disorders.
眼内炎症严重损害视力,而各种生理屏障,如角膜屏障,会阻碍眼内药物的输送效果。在本文中,我们提出了一种简单的方法来制备可溶解的混合微针 (MNs) 贴片,以有效地输送姜黄素来治疗眼内炎症性疾病。首先将水不溶性姜黄素封装到具有高抗炎能力的聚合物胶束中,然后使用简单的微成型方法将其与透明质酸 (HA) 结合以创建可溶解的混合 MNs 贴片。傅里叶变换红外光谱 (FTIR)、差示扫描量热法 (DSC) 和 X 射线衍射 (XRD) 分析表明,姜黄素在 MNs 贴片中原位无定形分散。根据体外药物释放研究,所提出的 MNs 贴片在 8 小时内提供了持续的药物释放。在体内局部应用后,MNs 贴片在角膜前的滞留时间延长至 3.5 小时以上,表现出良好的眼相容性。此外,这种 MNs 贴片可以可逆地穿透角膜上皮,在角膜表面产生一系列微通道,从而提高眼部生物利用度。更重要的是,与姜黄素眼药水相比,MNs 贴片在兔内毒素性葡萄膜炎 (EIU) 模型中显示出改善的治疗效果,通过减少 CD45 白细胞和 CD68 巨噬细胞等炎症细胞的渗透,证明了其在治疗不同类型眼内疾病方面的潜在应用价值。总之,MNs 贴片作为一种高效的眼部药物输送系统,通过局部应用可能成为一种有前途的治疗方法。