Abstract
Purpose:
We hypothesize that dexamethasone, a potent steroid frequently used for chorioretinal diseases, could be covalently attached to porous silicon particles and used as a long-lasting intravitreal delivery platform. The current study evaluates the feasibility chemical synthesis and potential application of this platform for treatment of posterior segment of eye diseases.
Methods:
Porous silicon microparticles were prepared by electrochemical etch of highly doped, (100)-oriented p-type silicon wafers in a 48% aqueous HF:ethanol electrolyte solution. The fresh etched porous silicon was heated at 800C in a furnace chamber for 2 hour in a ceramic boat for complete oxidation (from Si to SiO2). The particles were then functionalized with an amine group and a carboxylic acid group for drug loading (OPS-CO2H). Dexamethasone was covalently loaded to the surface of the porous silicon particles through functional group of COOH.
Results:
Dexamethasone loading by covalent attachment was confirmed by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy using a Nicolet 6700 FT-IR spectrometer with Smart-ATR attachment. As determined by thermogravimetric analysis (TGA), the mass loading of dexamethasone by covalent attachment was 134 ± 13 μg per mg of the particles, while only 16 ± 1 μg/mg particles for physical adsorption loading. In an in-vitro release study, porous silicon covalently loaded dexamethasone demonstrated a sustained release course of 90 days (Clast=9ng/mL), but concurrent control of free drug or adsorption loading showed a typical first-order release in a course of 14 days (Clast=9 ng/mL and 5 ng/mL).
Conclusions:
Porous silicon particles covalently loaded with dexamethasone may be a promising sustained intravitreal delivery system for dexamethasone and can be implemented for many chorioretinal diseases.
Keywords: 763 vitreous •
688 retina •
608 nanomedicine