Gade Shilpkala, Vora Lalitkumar K, Thakur Raghu Raj Singh
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, UK.
Methods. 2025 Feb;234:196-210. doi: 10.1016/j.ymeth.2024.12.004. Epub 2024 Dec 21.
Effective drug delivery to the posterior segment of the eye remains a challenge owing to the limitations of conventional methods such as intravitreal injections, which are associated with significant side effects. This study explored the use of hollow microneedles (HMNs) for localized intrascleral drug delivery as a minimally invasive alternative. Stainless steel HMNs with bevel angles of 30°, 45°, 60°, and 75° were fabricated using wire electron discharge machining. The penetration force of these HMNs in ex vivo porcine sclera was assessed using a texture analyser, revealing that the 60° bevel angle required the lowest force (<2N), making it optimal for scleral penetration. To ensure precision in drug delivery, 3D-printed adapters were developed to control the injection angles and volumes. The distribution of a model dye, rhodamine B, was studied via digital imaging, multiphoton microscopy, and confocal microscopy. The results showed that HMNs with a 60° bevel angle could penetrate the sclera to a depth of approximately 450 µm at a 45° injection angle, providing enhanced distribution within the scleral layers. This study confirmed that the use of HMNs enables effective and controlled intrascleral drug delivery, resulting in the formation of localized depots with minimal tissue damage. This research demonstrates the potential of HMNs as a promising alternative to traditional ocular drug delivery methods, offering improved bioavailability and the potential to reduce patient discomfort.
由于传统方法（如玻璃体内注射）存在局限性且伴有严重副作用，将药物有效递送至眼后段仍然是一项挑战。本研究探索了使用中空微针（HMNs）进行局部巩膜内药物递送作为一种微创替代方法。使用线电极放电加工制造了斜角为30°、45°、60°和75°的不锈钢HMNs。使用纹理分析仪评估这些HMNs在离体猪巩膜中的穿透力，结果显示60°斜角所需的力最低（<2N），使其最适合巩膜穿透。为确保药物递送的精确性，开发了3D打印适配器以控制注射角度和体积。通过数字成像、多光子显微镜和共聚焦显微镜研究了模型染料罗丹明B的分布。结果表明，60°斜角的HMNs在45°注射角度下可穿透巩膜至约450μm的深度，在巩膜层内提供增强的分布。本研究证实，使用HMNs能够实现有效且可控的巩膜内药物递送，从而在组织损伤最小的情况下形成局部贮库。这项研究证明了HMNs作为传统眼部药物递送方法的一种有前景的替代方法的潜力，可提高生物利用度并有可能减轻患者不适。
