Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon.

Abstract Daunorubicin (DNR) is an effective inhibitor of an array of proteins involved in neovascularization, including VEGF and PDGF. These growth factors are directly related to retina scar formation in many devastating retinal diseases. Due to the short vitreous half-life and narrow therapeutic window, ocular application of DNR is limited. It has been shown that a porous silicon (pSi) based delivery system can extend DNR vitreous residence from a few days to 3 months. In this study we investigated the feasibility of altering the pore size of the silicon particles to regulate the payload release. Modulation of the etching parameters allowed control of the nano-pore size from 15 nm to 95 nm. In vitro studies showed that degradation of pSiO 2 increased with increasing pore size and the degradation of pSiO 2 was approximately constant for a given particle type. The degradation of pSiO 2 with 43 nm pores was significantly greater than the other two particles with smaller pores, judged by observed and normalized mean Si concentration of the dissolution samples (44.2 ± 8.9 vs 25.7 ± 5.6 or 21.2 ± 4.2 μg/mL, p  In vitro dynamic DNR release revealed that pSiO 2 –CO 2 H:DNR (porous silicon dioxide with covalent loading of daunorubicin) with large pores (43 nm) yielded a significantly higher DNR level than particles with 15 or 26 nm pores (13.5 ± 6.9 ng/mL vs. 2.3 ± 1.6 ng/mL and 1.1 ± 0.9 ng/mL, p  in vitro dynamic release, 54% of the pSiO 2 –CO 2 H:DNR particles still remained in the dissolution chamber by weight. In vivo drug release study demonstrated that free DNR in the vitreous at post-injection day 14 was 66.52 ng/mL for 95 nm pore size pSiO 2 –CO 2 H:DNR, 10.76 ng/mL for 43 nm pSiO 2 –CO 2 H:DNR, and only 1.05 ng/mL for 15 nm pSiO 2 –CO 2 H:DNR. Pore expansion from 15 nm to 95 nm led to a 63 fold increase of DNR release (p  2 covalently loaded with DNR by engineering the nano-pore size of pSi.