A New Tissue-polymer Hybrid Drug Delivery System for Artificial Corneas

Abstract

Purpose: : We developed and evaluated a new hybrid tissue-polymer drug delivery system using lyophilized cornea and synthetic hydrogel. The feasibility of this system as a carrier and a drug delivery system for an artificial cornea (Boston Keratoprosthesis) was evaluated in vitro while non-modified cornea tissue was used as a control.

Methods: : Corneal tissue from the eye bank was first lyophilized. The tissue-polymer hybrid was synthesized by reconstituting the lyophilized cornea in a norfloxacin-loaded hydrogel solution followed by polymerization using external heat (65^oC) and Azo-Iso-Butyrodinitrile (AIBN) as a free radical initiator. Four different tissue-hydrogel compositions of varying hydrophobicity were synthesized and evaluated over one month for the swelling and drug release profile. Quantitative analysis of drug concentration was achieved using UV-Vis Spectrophotometry. The hybrid system was further characterized using optical and electron microscopy. Unmodified cornea tissue was used as a control. The mechanical strength and suture characteristics of the hybrid system and unmodified cornea were evaluated as a carrier for Boston K-pro using an artificial anterior chamber.

Results: : Both the hybrid-system and the control show excellent mechanical properties as carriers for the Boston K-pro. They withstood similar challenges of intrachamber pressures (50-70 mmHg) for wound stability. In vitro drug release analysis demonstrates a longer and more controlled drug release profile for the hybrid system as compared to the control. The most hydrophobic hybrid construct shows a release that is above the MIC 90 of Staphylococcus epidermidis for the first two days.

Keywords: keratoprostheses