Tolerability of silica microparticle gels as drug delivery vehicles

Aims/Purpose: Over the past decades, polymeric particles have become widespread in the field of drug delivery. Silica microparticles (SiMPs) are biodegradable—silicic acid being the main degradation product—and can release medication sustainably for a long period of time. Our aim was to determine the effects of soluble silicic acid on in vitro models of human epithelial cells. Methods: HCE‐2 and ARPE‐19 cells were exposed to serial dilutions of silicic acid produced by dissolving silica hydrogel in PBS, and cell viability was assessed after 24, 48 and 72 h of incubation. Cell viability data were provided by AlamarBlue assay, while membrane integrity was analysed through LDH release. For more information on the silicic acid impact on cellular stress, we assayed biochemical markers, such as IL‐6, IL‐8, MCP‐1, Caspase‐3 and Hsp‐70, using specific ELISAs. Results: AlamarBlue assay did not show any statistical differences in survival rate between the control group and maximum 30 μg/mL silicic acid in all timepoints in ARPE‐19 cells (24 h 95.42 ± 4.81%, 48 h 87.55 ± 6.48% and 72 h 97.64 ± 6.38%) and HCE‐2 cells (24 h 97.38 ± 5.97%, 48 h 100.81 ± 8.32% and 72 h 101.73 ± 2.62%). Additionally, we did not detect any toxic changes in LDH release test in ARPE‐19 cells in 24, 48 and 72 h time points (30 μg/mL silicic acid: 24 h 9.0 ± 11.5%, 48 h 10.4 ± 13.4% and 72 h 13.8 ± 16.6%). The LDH release data in treated (max. 30 μg/mL) HCE‐2 cells were comparable to control cells. Assessed inflammatory markers mostly were similar as well when comparing control and treatment groups, although IL‐6, MCP‐1, Caspase‐3 and Hsp‐70 showed increased values with time. Conclusions: Our results do not show major cytotoxicity of silicic acid on the two different epithelial cell lines, nor did not induce stress or inflammatory markers. Therefore, these findings support the use of our novel SiMPs as drug delivery vehicles in the treatment of ophthalmic diseases.