Toffoletto Nadia, Salema-Oom Madalena, Anguiano Igea Soledad, Alvarez-Lorenzo Carmen, Saramago Benilde, Serro Ana Paula
Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Avenue Rovisco Pais, 1049-001 Lisbon, Portugal.
Centro de Investigação Interdisciplinar Egas Moniz, Instituto Universitário Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal.
Pharmaceutics. 2021 Jun 28;13(7):976. doi: 10.3390/pharmaceutics13070976.
Pseudophakic cystoid macular edema (PCME), caused by chronic inflammation, is the most common cause of visual impairment in the medium-term after cataract surgery. Therefore, the prophylactic topical administration of combined steroidal and non-steroidal anti-inflammatory drugs is commonly done. Drug-eluting intraocular lenses (IOLs) gained interest as an efficient way to overcome the compliance issues related to the use of ocular drops without the need for additional surgical steps. The incorporation of functional monomers and molecular imprinting were herein applied to design hydrogels suitable as IOLs and able to co-deliver steroidal (dexamethasone sodium phosphate) and non-steroidal (bromfenac sodium) drugs. The incorporation of N-(2-aminopropyl) methacrylamide (APMA) increased the drug uptake and improved the in vitro release kinetics. Imprinting with bromfenac resulted in a decreased drug release due to permanent drug bonding, while imprinting with dexamethasone increased the amount of dexamethasone released after dual-drug loading. The application of a mathematical model to predict the in vivo drug release behavior suggests the feasibility of achieving therapeutic drug concentrations of bromfenac and dexamethasone in the aqueous humor for about 2 and 8 weeks, respectively, which is compatible with the current topical prophylaxis after cataract surgery.
人工晶状体性黄斑囊样水肿(PCME)由慢性炎症引起,是白内障手术后中期视力损害的最常见原因。因此,通常会预防性局部应用甾体类和非甾体类抗炎药。药物洗脱人工晶状体(IOL)作为一种有效的方法引起了人们的兴趣,它可以克服与使用眼药水相关的依从性问题,而无需额外的手术步骤。本文应用功能性单体的掺入和分子印迹技术来设计适合作为IOL的水凝胶,并能够共同递送甾体类药物(地塞米松磷酸钠)和非甾体类药物(溴芬酸钠)。N-(2-氨丙基)甲基丙烯酰胺(APMA)的掺入增加了药物摄取并改善了体外释放动力学。用溴芬酸进行印迹由于药物的永久结合导致药物释放减少,而用地塞米松进行印迹则增加了双药负载后地塞米松的释放量。应用数学模型预测体内药物释放行为表明,在房水中分别达到溴芬酸和地塞米松治疗药物浓度约2周和8周是可行的,这与目前白内障手术后的局部预防措施相符。