Experimental study on surface modification of intraocular lens by cyclosporine A-loaded chitosan nanoparticle

Abstract

Background Posterior capsular opacification (PCO) following cataract extracapsular extraction is a major cause of the reduction of visual acuity.Topical administration of eye drops is a research hotspot for the prevention of PCO.Objective This study was to evaluate the release of cyclosporine A-loaded chitosan nanoparticles (CyA-CS-NP) by ionic gelation in vitro and its feasibility of modification of the surface of polymethylmethacrylate intraocular lens (PMMA IOL) with CyA-CS-NP.Methods The CS-NP and CyA-CS-NP were prepared by ionic gelation of CS with sodium tripolyphosphate.The characteristics of CS-NP,such as the appearance and mean size,and drug entrapment efficient (EE),loading capacity (LC),and the drug release were studied ; the CyA content on the IOL surface was detected by high performance liquid chromatography (HPLC).The IOL surface modified with CyA-CS-NP was observed by scanning electron microscope and X-ray photoelectron spectroscopy technique (XPS),the changes of elements and chemical bond types between simple plasma processed IOL and CyA-CS-NP modified IOL were analyzed.The transmittance at the wavelength of 360-490 nm and refraction of IOL were detected using back focal length method and spectrophotometer,and the effective resolution of IOL was evaluated according to the instruction of ISO/CD 11979-2.Loops anti fatigue test of IOL referred to the criteria of ISO/CD 11979-3.Results The CS-NP and CyA-CS-NP showed monodisperse,uniform appearance similar to spherical shape with a mean size of (158±18) nm and (219±29) nm,respectively.The CyA-CS-NP had high CyA association efficiency and loading capacity (64.2％ and 7.6％).In vitro release study revealed a fast release on the first day followed by a increased drug release during an 11-day following up.The sustained release was approximately 46.6％ at day 1 and 77.7％ at day 12,respectively.The surface of IOLs with cling film was smooth without CS-NP;while the edge of IOLs appeared a layer of CyA-CS-NP after modification.XPS analysis displayed some elements such as phosphonium,CNH2 and O =CN that appeared on the modified surface,indicating that CyA-CS-NP existed on the surface of IOLs edge.The mean quality of CyA on three IOLs surface after modification was 171.88 μg.The diopter,distinguishing ability and transmittance of modified IOL were (16.64±0.23) D,(90.28 ± 0.25) ％ and (73.57 ±0.62) ％,and those of unmodified IOL were (16.62±0.29) D,(90.28±0.21) ％,(73.61±0.60)％,without significant differences between them (t =0.381,0.078,2.291,all at P ＞ 0.05).The antifatigue ability of loops complied with the criteria of ISO/CD 11979-3.Conclusions The optical property and antifatigue ability of loops of the edge-modified IOLs by CyA-CS-NP reach the normal standard and meet the requirement of clinic application.The edge-modified IOLs by CyA-CS-NP can be a delivery system for intraocular drug release. Key words: Chitosan nanoparticle; Cyclosporin A; Intraocular lens; Ionic gelation; Surface modification