Madhusudhan Sharadha, Gupta Naresh Vishal, Rahamathulla Mohamed, Chidambaram Saravana Babu, Osmani Riyaz Ali M, Ghazwani Mohammed, Ahmed Mohammed Muqtader, Farhana Syeda Ayesha, Sarhan Mohammed Y, Tousif Ahmed Hediyal
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India.
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Pharmaceutics. 2023 Oct 4;15(10):2419. doi: 10.3390/pharmaceutics15102419.
Diabetic retinopathy (DR) is a microvascular complication associated with vascular endothelial growth factor (VEGF) overexpression. Therapeutic delivery to the retina is a challenging phenomenon due to ocular biological barriers. Sorafenib tosylate (ST) is a lipophilic drug with low molecular weight, making it ineffective at bypassing the blood-retinal barrier (BRB) to reach the target site. Cubosomes are potential nanocarriers for encapsulating and releasing such drugs in a sustained manner. The present research aimed to compare the effects of sorafenib-tosylate-loaded cubosome nanocarriers (ST-CUBs) and a sorafenib tosylate suspension (ST-Suspension) via subconjunctival route in an experimental DR model. In this research, ST-CUBs were prepared using the melt dispersion emulsification technique. The distribution of prepared nanoparticles into the posterior eye segments was studied with confocal microscopy. The ST-CUBs were introduced into rats' left eye via subconjunctival injection (SCJ) and compared with ST-Suspension to estimate the single-dose pharmacokinetic profile. Streptozotocin (STZ)-induced diabetic albino rats were treated with ST-CUBs and ST-Suspension through the SCJ route once a week for 28 days to measure the inhibitory effect of ST on the diabetic retina using histopathology and immunohistochemistry (IHC) examinations. Confocal microscopy and pharmacokinetic studies showed an improved concentration of ST from ST-CUBs in the retina. In the DR model, ST-CUB treatment using the SCJ route exhibited decreased expression levels of VEGF, pro-inflammatory cytokines, and adhesion molecules compared to ST-Suspension. From the noted research findings, it was concluded that the CUBs potentially enhanced the ST bioavailability. The study outcomes established that the developed nanocarriers were ideal for delivering the ST-CUBs via the SCJ route to target the retina for facilitated DR management.
糖尿病视网膜病变（DR）是一种与血管内皮生长因子（VEGF）过度表达相关的微血管并发症。由于眼部生物屏障的存在，向视网膜进行治疗性给药是一个具有挑战性的问题。甲苯磺酸索拉非尼（ST）是一种亲脂性药物，分子量较低，难以有效绕过血视网膜屏障（BRB）到达靶位点。立方液晶纳米粒是一种潜在的纳米载体，能够持续包裹和释放此类药物。本研究旨在比较在实验性DR模型中，通过结膜下途径给予载甲苯磺酸索拉非尼的立方液晶纳米粒（ST-CUBs）和甲苯磺酸索拉非尼混悬液（ST-Suspension）的效果。在本研究中，采用熔融分散乳化技术制备了ST-CUBs。利用共聚焦显微镜研究了制备的纳米颗粒在眼后段的分布情况。通过结膜下注射（SCJ）将ST-CUBs引入大鼠左眼，并与ST-Suspension进行比较，以评估单剂量药代动力学特征。用链脲佐菌素（STZ）诱导的糖尿病白化大鼠，每周通过SCJ途径用ST-CUBs和ST-Suspension治疗一次，共28天，通过组织病理学和免疫组织化学（IHC）检查来测量ST对糖尿病视网膜的抑制作用。共聚焦显微镜和药代动力学研究表明，ST-CUBs中的ST在视网膜中的浓度有所提高。在DR模型中，与ST-Suspension相比，通过SCJ途径给予ST-CUB治疗可降低VEGF、促炎细胞因子和黏附分子的表达水平。根据上述研究结果得出结论，立方液晶纳米粒可能提高了ST的生物利用度。研究结果表明，所开发的纳米载体是通过SCJ途径递送ST-CUBs以靶向视网膜从而促进DR管理的理想载体。
