Rosmarinic acid, a plant-derived compound with antiangiogenic activity, can be applied for the treatment of ocular diseases related to neovascularization, such as diabetic retinopathy, macular edema, and age-related macular degeneration. These diseases represent the leading causes of blindness worldwide if they are not properly treated. Intravitreal devices allow for localized drug delivery to the posterior segment, increasing the drug bioavailability and promoting extended release, thus, reducing side effects and enhancing the patient's compliance to the treatment. In this work, rosmarinic acid-loaded poly lactic-co-glycolic acid intraocular implants were developed with a view for the treatment of ocular neovascularization. Physical-chemical, biocompatibility, and safety studies of the implants were carried out in vitro and in vivo as well as an evaluation of the antiangiogenic activity in a chorioallantoic membrane assay. Data obtained showed that rosmarinic acid released from the implants was quantified in the vitreous for 6 weeks, while when it was in the solution formulation, after 24 h, no drug was found in the vitreous. The delivery device did not show any sign of toxicity after clinical evaluation and in electroretinographic findings. Histological analysis showed normal eye tissue. Rosmarinic acid released from implants reduced 30% of new vessel's formation. The intravitreal implant successfully allowed for the prolonged release of rosmarinic acid, was safe to rabbits eyes, and demonstrated activity in vessel reduction, thus demonstrating potential in preventing neovascularization in ophthalmic diseases.

中文翻译：

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迷迭香酸玻璃体内植入物：眼部新生血管形成的新治疗方法


迷迭香酸是一种具有抗血管生成活性的植物源化合物，可用于治疗与新生血管形成相关的眼部疾病，如糖尿病视网膜病变、黄斑水肿和年龄相关性黄斑变性。如果治疗不当，这些疾病是全世界失明的主要原因。玻璃体内装置可以将药物局部输送到眼后段，提高药物的生物利用度并促进缓释，从而减少副作用并提高患者对治疗的依从性。在这项工作中，开发了负载迷迭香酸的聚乳酸-乙醇酸共聚物眼内植入物，旨在治疗眼部新生血管形成。在体外和体内对植入物进行了物理化学、生物相容性和安全性研究，并在绒毛尿囊膜测定中评估了抗血管生成活性。获得的数据显示，6周内，植入物释放的迷迭香酸在玻璃体中被量化，而当其在溶液制剂中时，24小时后，玻璃体中没有发现药物。经过临床评估和视网膜电图检查结果后，该输送装置没有显示出任何毒性迹象。组织学分析显示眼组织正常。植入物释放的迷迭香酸可减少 30% 的新血管形成。玻璃体内植入物成功地实现了迷迭香酸的长期释放，对兔眼安全，并显示出血管减少活性，从而显示出预防眼科疾病新生血管形成的潜力。