Kassumeh Stefan A, Wertheimer Christian M, von Studnitz Annabel, Hillenmayer Anna, Priglinger Claudia, Wolf Armin, Mayer Wolfgang J, Teupser Daniel, Holdt Lesca M, Priglinger Siegfried G, Eibl-Lindner Kirsten H
a Department of ophthalmology , Ludwig-Maximilians-University , Munich , Germany.
b Institute of Laboratory Medicine , Ludwig-Maximilians-University Munich , Munich , Germany.
Curr Eye Res. 2018 Jun;43(6):702-708. doi: 10.1080/02713683.2018.1437455. Epub 2018 Feb 16.
Posterior capsule opacification (PCO) still represents the main long-term complication of cataract surgery. Research into pharmacologic PCO prophylaxis is extensive. One promising candidate drug is methotrexate (MTX). Our aim is to determine the in vitro feasibility of MTX-loaded poly(lactic-co-glycolic) (PLGA) biomatrices sprayed on intraocular lenses (IOLs) as a drug-delivery implant.
Hydrophilic and hydrophobic acrylic IOLs were spray-coated with MTX-loaded PLGA. Unsprayed, solvent only, and solvent-PLGA-sprayed IOLs served as controls. All IOLs were evaluated for their growth-inhibiting properties in an in vitro anterior segment model and the ex vivo human capsular bag. The release kinetics of MTX from the IOLs was determined. The toxicity of MTX on corneal endothelial cells was evaluated by using a dye reduction colorimetric assay. MTX was also used in a scratch assay.
MTX-PLGA-IOL showed a significant difference in cell proliferation and migration compared with all controls in the anterior segment model (p < 0.001) and in the human capsular bag model (p = 0.04). No difference in viability was observed on corneal endothelial cells (p = 0.43; p = 0.61). MTX significantly inhibited cells in the scratch assay (p = 0.02). At all measured points, the released MTX dose remained above EC50 and below the toxic dose for the endothelium.
In view of the strong inhibition of PCO in vitro with the lack of toxic effects on a corneal cell line, MTX encapsulating microspheres seem to be a promising method for modifying IOL.
后囊膜混浊(PCO)仍是白内障手术的主要长期并发症。针对PCO的药物预防研究广泛。一种有前景的候选药物是甲氨蝶呤(MTX)。我们的目的是确定将负载MTX的聚乳酸-乙醇酸共聚物(PLGA)生物基质喷涂在人工晶状体(IOL)上作为药物递送植入物的体外可行性。
用负载MTX的PLGA对亲水和疏水丙烯酸IOL进行喷雾涂层。未喷涂、仅喷涂溶剂以及喷涂溶剂-PLGA的IOL作为对照。在体外眼前节模型和离体人囊袋中评估所有IOL的生长抑制特性。测定MTX从IOL中的释放动力学。通过染料还原比色法评估MTX对角膜内皮细胞的毒性。MTX也用于划痕试验。
在眼前节模型(p < 0.001)和人囊袋模型(p = 0.04)中,MTX-PLGA-IOL与所有对照相比,在细胞增殖和迁移方面存在显著差异。在角膜内皮细胞上未观察到活力差异(p = 0.43;p = 0.61)。在划痕试验中MTX显著抑制细胞(p = 0.02)。在所有测量点,释放的MTX剂量保持在EC50以上且低于内皮细胞的毒性剂量。
鉴于MTX在体外对PCO有强烈抑制作用且对角膜细胞系无毒性作用,MTX包裹微球似乎是一种有前景的IOL修饰方法。