Centro de Química Estrutural, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Centro de Investigação Interdisciplinar Egas Moniz, Instituto Universitário Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal.
Int J Pharm. 2021 May 1;600:120513. doi: 10.1016/j.ijpharm.2021.120513. Epub 2021 Mar 22.
Although cataract surgery is considered a safe procedure, post-surgery complications such as endophthalmitis and ocular inflammation, may occur. To prevent this, antibiotics and anti-inflammatories are prescribed in the form of eye drops during the post-operatory period, but they lead to a low drug bioavailability in target tissues. The objective of this work is to develop an intraocular lens (IOL) material to deliver simultaneously one antibiotic, moxifloxacin (MXF), and one anti-inflammatory, diclofenac (DFN), in therapeutic concentrations to prevent both complications. The IOL material was modified through the incorporation of functional monomers, as well as molecular imprinting with both drugs using the same functional monomers, namely acrylic acid (AA), methacrylic acid (MAA), 4-vinylpiridine (4-VP) and a combination of MAA + 4-VP. The best results were obtained with MAA. Molecular imprinting did not influence the drug release, except with AA. Application of a mathematical model predicted that the released MXF and DFN concentrations would stay above the pre-determined MIC of S. aureus and S. epidermidis and the minimum values of IC50 of COX-1 and COX-2, for 9 and 14 days, respectively. Antibacterial tests showed that the released antibiotic remained active. The physical properties of the drug-loaded MAA-hydrogel remained adequate. The developed system proved to be non-irritant and non-cytotoxic.
虽然白内障手术被认为是一种安全的手术,但术后可能会出现眼内炎和眼部炎症等并发症。为了预防这种情况,在术后期间会以眼药水的形式开抗生素和消炎药,但这导致目标组织中的药物生物利用度较低。这项工作的目的是开发一种人工晶状体 (IOL) 材料,以治疗浓度同时输送一种抗生素,莫西沙星 (MXF) 和一种消炎药,双氯芬酸 (DFN),以预防这两种并发症。IOL 材料通过掺入功能单体进行改性,同时使用相同的功能单体对两种药物进行分子印迹,即丙烯酸 (AA)、甲基丙烯酸 (MAA)、4-乙烯基吡啶 (4-VP) 和 MAA+4-VP 的组合。结果最好的是使用 MAA。分子印迹除了对 AA 外,不会影响药物释放。应用数学模型预测,释放的 MXF 和 DFN 浓度将保持在金黄色葡萄球菌和表皮葡萄球菌的预定 MIC 以及 COX-1 和 COX-2 的最小 IC50 值之上,分别为 9 天和 14 天。抗菌测试表明,释放的抗生素仍然具有活性。载药 MAA 水凝胶的物理性质仍然足够。开发的系统被证明是非刺激性和非细胞毒性的。