Preparation Of Layer-by-layer Self-assembled Drug-loaded Intraocular Lens And Its Application Study

Background:Surface modification of intraocular lens (IOL) has been widely investigated to prevent various complications induced by cataract surgery, such as posterior capsule opacification (PCO), endophthalmitis, and cystoid macular edema (CME), among which endophthalmitis is the most serious one.Aims:(1) To prepare antibiotic-loaded multilayers on surface of hydrophobic acrylic intraocular lens through a lay-by-layer self-assembly technique;(2) To test the physicochemical, optical, and mechanical properties of the functionalized intraocular lens, as well as their cytotoxicity and in vitro bactericidal performance.Methods:The surface of hydrophobic acrylic IOL was functionalized with polyethylenimine-(hyaluronic acid-poly-L-lysine/tobramycin or amikacin)n-HA multilayers using atmospheric plasma glow discharge, followed by layer-by-layer self-assembly. Hydrophilicity of the modified lens was tested by water contact angle measurement. The change of mass, thickness, and viscoelasticity of the multilayers with respect to the number of layers was explored by quartz crystal microbalance (QCM), which verifies the exponential growth of LbL multilayers. The morphology of the functionalized IOLs was characterized by field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM), by which surface roughness was recorded. Surface elemental compositions of the lens were studied using X-ray photoelectron spectroscopy (XPS). The optical and mechanical properties of the IOLs were tested and compared with the National Quality Test Standard of IOL (YY-0290). Human lens epithelial cells (hLEC) and human retinal pigment epithelial cells (ARPC-19) were cultured in DMEM-F12, respectively, in which the drug loaded IOLs were soaked for 24 hours. Then cell counting kit-8 (CCK-8) was used to examine the cytotoxicity in vitro. Staphylococcus epidermidis was cultured with the new IOLs for 24 hours, and the in vitro bactericidal performance of IOLs was investigated using Live/Dead BacLight Bacterial vitality kit.Results:Water contact angle measurement confirms that the surface of IOLs become more hydrophilic after modification. QCM corroborates the successful assembly of multilayers on the surface, and the mass and thickness of the multilayers is increased exponentially with the number of layers, which suggests that the efficiency of modification can be greatly enhanced. SEM and AFM results show that there is no significant change in surface morphology of the IOLs before and after modification. XPS validates the change of surface elemental composition, which confirms that the surface is successfully modified by multilayers. The optical and mechanical properties of the new IOLs were tested and the results meet the National Quality Test Standard of IOL(YY-0290). CCK-8 experiment shows that the new IOLs has no in vitro cytotoxicity to hLEC and ARPE-19. In contrast, S. epidermidis was killed by the drug-loaded IOLs in vitro, which confirms the new IOLs as promising bactericidal lens.Conclusions:Polyethylenimine-(hyaluronic acid-poly-L-lysine/tobramycin or amikacin)n-HA multilayers were successfully loaded on the surface of IOLs using layer-by-layer self assembly. The multilayers were more hydrophilic and had similar surface morphology and roughness compared with unmodified lens. The mass and thickness of multilayers were exponentially increased with the number of layers. The optical and mechanical properties of IOLs met the National Quality Test Standard of IOL. The new IOLs were proved to be non-cytotoxic to hLEC and ARPE-19, while exhibit a good bactericidal performance for S.eperdimidis.