From: Strategies for ocular siRNA delivery: Potential and limitations of non-viral nanocarriers
Target | Carrier | Disease | Model | Delivery method | Results | Implications for ocular diseases | Reference |
---|---|---|---|---|---|---|---|
IκB kinase beta (IKKβ) | Cationic nano-copolymers CS-g-(PEI-b-mPEG) | Glaucoma filtration surgery | Rhesus monkey | Subconjunctival injection | Marked reduction in subconjuctival scarring with siRNA treatment in monkeys with trabeculectomy; higher blebs with siRNA compared to PBS treatment; less fibrosis and less destruction of local tissue in siRNA-treated eyes | Improved surgical outcome in glaucoma filtration surgery (less scarring) | [34] |
IκB kinase beta (IKKβ) | Cationic nano-copolymers CS-g-(PEI-b-mPEG) | Glaucoma filtration surgery | Human | In vitro transfection | Downregulation of IKKβ at the mRNA and protein levels; nuclear factor-κB (NF-κB) inhibited in human Tenon’s capsule fibroblasts | Decreased scar formation following glaucoma filtration surgery | [33] |
VEGFR1 | PEGylated liposome- protamine- hyaluronic acid nanoparticles (PEG-LPH-NP) | Choroidal neo-vascularization | Human RPE cells (ARPE19) and rats | Intravitreal injection | Reduced laser-induced CNV area in rats by PEG-LPH-NP-S nanoparticles (anti-VEGFR1 siRNA) compared with naked siRNA and PEG-LPH-NP (negative siRNA); downregulated VEGFR1 expression in human RPE cells with siRNA compared to naked siRNA and control group; no significant retinal toxicity | Delivery of siRNA to decrease CNV with low toxicity | [36] |
Non-specific commercial siRNA | Transit- TKO transfection reagent | Healthy mice | Mouse | Intravitreal injection | Combination of siRNA with Transit - TKO transfection reagent penetrated through the inner limiting membrane into the retina and accumulated in ganglion cell layer | Uniform delivery to retinal through intravitreal injections of siRNA using commercial reagents | [94] |