Sustained Release of a Monoclonal Antibody From Electrochemically Prepared Porous Silica for the Treatment of Age Related Macular Degeneration

Abstract

Purpose: : To overcome the limitations of current anti-VEGF therapy, which entails frequent intravitreal injections, we have synthesized biocompatible and biodegradable nanoporous silicon dioxide (SiO₂) microparticles and used them to load and release the monoclonal antibody bevacizumab (Avastin®). These particles allow for high drug loading, controlled release, as well as a simple optical method for monitoring release in a clinical setting.

Methods: : The biocompatible form of porous SiO₂ was prepared by the electrochemical etch and subsequent thermal oxidation of a single crystalline silicon wafer. The inner pore walls of the porous SiO₂ matrix possess a negative surface charge, which spontaneously adsorbs the antibody from aqueous buffered (pH 7.4) solution. The drug loading was monitored and verified by optical interferometric measurements. In vitro drug release profiles were characterized by micro bicinchoninic acid protein assay.

Results: : The nanostructured delivery system described here provides a sustained release of the monoclonal antibody where approximately 60% of drug is released over a period of 2 weeks. Calculations based on the in vitro antibody release data and using a therapeutic model involving the treatment of age-related macular degeneration by direct intravitreal injection indicate that this approach could maintain therapeutic levels of drug in the eye for > 4 months.

Conclusions: : Bevacizumab loaded intravitreally injected porous silicon nanoparticles are capable of releasing bevacizumab for a period of over four months in the therapeutic range. Such a drug delivery device can be injected thru a small gage needle and can be monitored as the reflection spectrum of the loaded nanoparticles changes during drug release.

Keywords: age-related macular degeneration • retina • vitreous