Abstract
Purpose :
In recent years, porous silicon (pSi) has emerged as a novel drug carrier for controlled drug release. Compared with the traditional drug delivery vehicles such as liposomes or polymer particulates, pSi offers tunable nano-scaled pores for various sized payloads and adjustable drug release rates. The current study aims to characterize the ocular properties of sol-gel pSi particles and their degradation product, silicic acid (SiOH4).
Methods :
Two concentrations (low, 2.5µg/mL; high, 25µg/mL) of SiOH4 at two incubation durations (short, 5 days; long, 5 weeks) were designed to assess the safety concentration and the safety of exposure time. EA.hy926 cells were exposed to SiOH4 and cytotoxicity was determined by WST-1 assay. In addition, various particle and pore sizes of sol-gel pSiO2 particles were monitored in a daily static release to discover the SiOH4 dissolution kinetics before 8mg of intravitreal injection in 4 rabbit eyes.
Results :
WST-1 cytotoxicity data demonstrated that SiOH4 at 2.5µg/mL was not cytotoxic but 25µg/mL was when compared to the control (p<0.0001). The cells with five-week exposure to SiOH4 showed cytotoxicity when compared with 5-day exposure (p<0.0001) (Figure 1). SiOH4 release profiles from the three formulations of pSiO2 particles is shown in figure 2. SiOH4 dissolution rates from the sol-gel pSiO2 particles were pore-size dependent (p<0.0001). Four rabbit eyes with 8mg intravitreal dose did not show any toxicity in clinical and ERG exams.
Conclusions :
The in vitro study suggested SiOH4 cytotoxicity at high concentration or long-term exposure; however, in vivo study revealed minimal toxicity. SiOH4 dissolution rate from the pSiO2 particles is pore-size dependent both in vitro and in vivo.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.