Design of Accommodating Intra-ocular Lens--Synthesis of Organosilica Nanoparticles

Abstract

 

Purpose

 

We are designing nanocomposites for in situ gelling materials to fill the lens capsular bag (Ravi N, et al., 2005). The nanocomposites use a rigid polymer backbone to mimic the cytoskeletal lens components mixed with nanoparticles to mimic the lens crystallins. To be suitable, the nanoparticles need to be of the correct size (<30 nm), and when dissolved at high concentration should match the lens crystallins in density (~1.08), refractive index (RI) (~1.4) and low modulus (< 5 Pa) and have to be compatible with the polymer backbone being utilized. We have been investigating organosilica materials for use in this application.

 

Methods

 

We have modified a published procedure ( Irmukhametova et al., Langmuir, 2012). We used fifteen reactions in a three-level full-factorial statistical design experiment of two factors (NaOH and water) to optimize the reaction. The reactions were set up using 750 uL of 3-mercaptopropyl-trimethoxysilane, (MPTS) with 20 mL dimethylsulfoxide as a solvent. NaOH and water were varied from 0.25-0.75 mmoles and 20-60 mmoles respectively. MPTS nanoparticles were surface modified using N-(2-hydroxyethyl) maleimeide (HEM) to conjugate with unbridged -SH molecules. Nanoparticle were sized by dynamic light scattering. Biocompatibility was done in tissue culture using retinal epithelial cells (ARPE-19).

 

Results

 

Figure 1 shows the number average (Navg) size of the nanoparticles from our statistical experiment. Higher amounts of NaOH resulted in decreased unreacted thiol groups (-SH). HEM modified nanoparticles from a reaction containing 0.50 mmoles of NaOH and 30 mmoles of water resulted in a Navg size particle of 21 nm (>90% 15-36 nm) before modification and 23 nm (>90% 15-36 nm) after modification. Measurements of the modified particles extrapolate to a 35 % w/w solution giving a RI of 1.4 with acceptable density. Nanoparticles tested using ARPE-19 cells at 0.5 mg/ml did not show significant toxicity.

 

Conclusions

 

Statistical design allowed for optimization of the nanoparticles with respect to size and number of unbridged -SH molecules available for surface modification. These nanoparticles were surface modified to stabilize the particles. Optical properties and density indicated that these materials have promise as biomimetics for crystallin proteins in nanocomposites for lens materials.

 

 

Figure 1. Plot of the number average size nanoparticles from the statistical design experiments

 

Keywords: 404 accommodation • 607 nanotechnology • 567 intraocular lens