title: Cytotoxicity assessment of porous silicon microparticles for ocular drug delivery.
abstract: Porous silicon (PSi) is a promising material for the delivery and sustained release of therapeutic molecules in various tissues. Due to the constant rinsing of cornea by tear solution as well as the short half-life of intravitreal drugs, the eye is an attractive target for controlled drug delivery systems, such as PSi microparticles. Inherent barriers ensure that PSi particles are retained in the eye, releasing drugs at the desired speed until they slowly break down into harmless silicic acid. Here, we have examined the in vitro cytotoxicity of positively and negatively charged thermally oxidized (TOPSi) and thermally carbonized (TCPSi) porous silicon microparticles on human corneal epithelial (HCE) and retinal pigment epithelial (ARPE-19) cells. In addition to ocular assessment under an inverted microscope, cellular viability was evaluated using the CellTiter Blue™, CellTiter Fluor™, and lactate dehydrogenase (LDH) assays. CellTiter Fluor proved to be a suitable assay but due to non-specific and interfering responses, neither CellTiter Blue nor LDH assays should be used when evaluating PSi particles. Our results suggest that the toxicity of PSi particles is concentration-dependent, but at least at concentrations less than 200μg/ml, both positively and negatively charged PSi particles are well tolerated by human corneal and retinal epithelial cells and therefore applicable for delivering drug molecules into ocular tissues.
authors.affiliation: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Eveliina
authors.initials: E
authors.lastname: Korhonen
authors.affiliation: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Rönkkö
authors.affiliation: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Hillebrand
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
authors.forename: Joakim
authors.initials: J
authors.lastname: Riikonen
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
authors.forename: Wujun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
authors.affiliation: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland. Electronic address: anu.kauppinen@uef.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
mesh_terms: D060433:Administration, Ophthalmic; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D016062:Porosity; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000502:physiology; D012825:Silicon / Q000008:administration & dosage* / Q000633:toxicity*
chemical_list: D004337:Drug Carriers; D012825:Silicon
keywords: Cell culture; Cytotoxicity; Eye; Microparticle; Porous silicon