Abstract
Purpose :
To design an innovative method by using intraocular lens (IOLs) as a drug delivery system for genistein (Gen) loaded nanostructured lipid carrier. The safety and efficacy of this system in the prevention of posterior capsular opacification (PCO) were investigated.
Methods :
The surface potentials of 6 commercial models of IOLs made by different materials (hydrophilic and hydrophobic acrylate, PMMA and silicone) were measured by electric force microscopy. Gen-NLCs with positive or negative charges were separately prepared using chitosan chlorides or sodium deoxycholate surface modification method. The morphology, particle size, zeta potentials, encapsulation efficiency, in vitro release and the inhibition effect on human lens epithelial cells (hLECs) proliferation were characterized. Gen-NLCs were incorporated with different models of IOLs (Gen-NLC-IOL) by soaking or covalent joint method. In vitro release of Gen-NLC-IOLs were compared and evaluated to optimize the system. The efficacy and safety of the system were further investigated in animal model.
Results :
The I20Imv and I10Imv of Gen-NLCs were successfully produced with a moderately increased particle size (from 82.30±4.02nm to 165.71±13.76nm), high encapsulation efficiency (all above 85%) and a spherical shape. An effective growth inhibitive effect on hLECs had been proven in vitro. As for Gen-NLC-IOL system, hydrophilic acrylic IOLs released the highest drugs among all the materials by soaking method and higher drug loading was observed by increasing surface charges of NLCs when IOL and NLC had opposite charge properties. The drug release could be significantly increased by covalent attaching SDC modified NLC onto hydrophilic acrylic IOLs compared to soaking method. In cataract surgery animal models, the concentrations of Gen-NLCs were detectable until 96h after surgery, which was much higher than those in the Gen-NLC anterior chamber injection group. No obvious regenerated cortex on posterior capsular member was seen 12 weeks after Gen-NLC-IOL implantation. No morphological changes could be detected in adjacent tissues by TEM.
Conclusions :
Covalent joint was a promising method for nanostructured lipid carrier of Gen loaded on hydrophilic acrylic IOLs. Intraocular Gen-NLC-IOL implatation was a controlled, effective, and safe administration system to prevent PCO in animal model.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.