Elsherbiny Sarah A, El-Kamel Amal H, Bakr Basant A, Heikal Lamia A
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt.
Drug Deliv Transl Res. 2025 Jul 11. doi: 10.1007/s13346-025-01914-9.
Glaucoma, a leading cause of irreversible blindness, is marked by elevated intraocular pressure (IOP) and retinal ganglion cell death. Traditional IOP-lowering eye drops often fail to penetrate the ocular barrier, leading to suboptimal outcomes. Microneedles (MN), offer a promising minimally invasive and localized alternative. Our study aimed to formulate a naturally-derived nanodelivery system using Luteolin-loaded colostrum-derived exosomes (LUT-EX) and propolis in MN arrays for better ocular delivery. The isolated exosomes were uniform, averaging 50.83 nm in size, with a zeta potential of -21.89 mV. LUT-EX showed a 48-h sustained release and high safety with an IC50 of 356.3 µg/mL. Integrating LUT-EX and propolis into MN arrays achieved optimal dissolution in over one minute and maintained mechanical strength under 30 N compression. LUT-EX@MN increased LUT permeation through scleral tissues 2.6-fold compared to gel matrix formulations. It also showed a sustained IOP-lowering effect reaching the normal IOP level in the first 3h and sustained over 7 days. The integrated system significantly reversed glaucoma-induced changes in TNF-α, IL-8, MYOC, NRF2, TIMP1, and IL-1β levels, resembling those of the healthy group. It also boosted antioxidant activity, increasing glutathione peroxidase by 1.6-fold compared to glaucomatous rabbits. Thus, our study highlighted that the integration of LUT-EX into microneedle arrays presents a groundbreaking dropless approach for localized glaucoma treatment, offering enhanced therapeutic efficacy. This platform could revolutionize glaucoma management, paving the way for more effective and targeted ocular therapies.
青光眼是不可逆失明的主要原因，其特征为眼压升高和视网膜神经节细胞死亡。传统的降眼压眼药水往往无法穿透眼部屏障，导致治疗效果欠佳。微针提供了一种有前景的微创且局部给药的替代方法。我们的研究旨在利用负载木犀草素的初乳来源外泌体（LUT-EX）和蜂胶制备一种天然来源的纳米递送系统，并将其整合到微针阵列中，以实现更好的眼部给药。分离得到的外泌体形态均一，平均大小为50.83 nm，ζ电位为-21.89 mV。LUT-EX显示出48小时的持续释放且安全性高，半数抑制浓度（IC5０）为356.3 μg/mL。将LUT-EX和蜂胶整合到微针阵列中，可在一分钟内实现最佳溶解，并在30 N的压力下保持机械强度。与凝胶基质制剂相比，LUT-EX@MN使木犀草素透过巩膜组织的渗透率提高了2.6倍。它还显示出持续的降眼压作用，在最初3小时内降至正常眼压水平，并持续7天以上。该整合系统显著逆转了青光眼引起的肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）、肌球蛋白（MYOC）、核因子E2相关因子2（NRF2）、金属蛋白酶组织抑制因子1（TIMP1）和白细胞介素-1β（IL-1β）水平的变化，使其与健康组相似。它还增强了抗氧化活性，与青光眼兔相比，谷胱甘肽过氧化物酶增加了1.6倍。因此，我们的研究强调，将LUT-EX整合到微针阵列中为青光眼的局部治疗提供了一种开创性的无滴剂方法，具有更高的治疗效果。该平台可能会彻底改变青光眼的治疗方式，为更有效、更有针对性的眼部治疗铺平道路。
