Superoxide Dismutase 1 Nanoparticles (Nano-SOD1) as a Potential Drug for the Treatment of Inflammatory Eye Diseases

Abstract

Inflammatory eye diseases remain the most common clinical problem in ophthalmology. The secondary processes associated with inflammation, such as overproduction of reactive oxygen species (ROS) and exhaustion of the endogenous antioxidant system, frequently lead to tissue degeneration, vision blurring, and even blindness. Antioxidant enzymes, such as copper–zinc superoxide dismutase (SOD1), could serve as potent scavengers of ROS. However, their delivery into the eye compartments represents a major challenge due to the limited ocular penetration. This work presents a new therapeutic modality specifically formulated for the eye on the basis of multilayer polyion complex nanoparticles of SOD1 (Nano-SOD1), which is characterized by appropriate storage stability and pronounced therapeutic effect without side reactions such as eye irritation; acute, chronic, and reproductive toxicity; allergenicity; immunogenicity; mutagenicity even at high doses. The ability of Nano-SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with a model immunogenic uveitis—the inflammation of the inner vascular tract of the eye. It was shown during preclinical studies that topical instillations of Nano-SOD1 were much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as corneal and conjunctival edema, iris hyperemia, and fibrin clots. Moreover, Nano-SOD1 penetrates into interior eye structures more effectively than SOD itself and retains enzyme activity in the eye for a much longer period of time, decreasing inflammation and restoring antioxidant activity in the eye. Thus, the presented Nano-SOD1 can be considered as a potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.

Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye

“…Superoxide dismutase -More effective compared to the free enzyme in decreasing immunogenic uveitis in rabbits -No signs of eye irritation in rabbits [81] Protamine, PEG-b-Polyglutamic acid Superoxide dismutase -High storage stability -Pronounced therapeutic effect without side reactions such as eye irritation -Penetration into anterior eye structures more effectively than the free enzyme [82] Tetronic 701,Synperonic PE/F127,Synperonic ® PE/P84 Lornoxicam -A sharp solubility increase from 0.0318 mg/mL up to more than 2.34 mg/mL, representing about a 73-fold increase -…”

“…Polymer nanomicelles could also serve as carriers of high molecular weight compounds, such as enzymes. These formulations designed for the drug delivery to the eye were described in [81,82]. Thus, the so-called "nanozyme" formed by self-assembly of the antioxidant enzyme, superoxide dismutase 1 (SOD1) with PEG-poly-L-lysine 50 block copolymer and further stabilized by cross-linking was used as a carrier for the delivery of SOD1 into ocular tissues for the treatment of inflammation processes in the eye.…”

“…Recently, double-coated SOD1-containing nanomicelles based on multilayer polyion complexes and called nanoSOD1 were synthesized [82], These cross-linked nanomicelles were characterized by high storage stability and pronounced therapeutic effect on immunogenic uveitis in rabbits without side reactions such as eye irritation; acute, chronic, and reproductive toxicity; allergenicity; immunogenicity, and mutagenicity even in high doses. It was shown during preclinical studies that topical instillations of nanoSOD1 were much more effective compared to the free enzyme in decreasing uveitis manifestations, such as corneal and conjunctival edema, iris hyperemia, and the amount of fibrin clots in the anterior chamber.…”

“…It was shown during preclinical studies that topical instillations of nanoSOD1 were much more effective compared to the free enzyme in decreasing uveitis manifestations, such as corneal and conjunctival edema, iris hyperemia, and the amount of fibrin clots in the anterior chamber. Moreover, it was shown that nanoSOD1 penetrated anterior eye structures more effectively than SOD1 itself and retained enzyme activity in the eye for a much longer period, decreasing inflammation and restoring antioxidant activity in the eye [82].…”

A Review of Ocular Drug Delivery Platforms and Drugs for Infectious and Noninfectious Uveitis: The Past, Present, and Future

“…Optimization with thiolation, amino acid modifications and PEGylation has improved corneal penetration of larger nanoparticles expanding the list of drugs that could be delivered to the eye with these aforementioned nanoparticles [ 99 , 100 ]. In other experimental data more specific to uveitis, topical polymeric nanoparticles loaded with triamcinolone or antioxidant enzymes such as superoxide dismutase have been shown to reduce clinical signs of uveitis in rabbits [ 101 , 102 ]. Subconjunctival, controlled-release, carboxyl-poly lactic-co-glycolic acid, steroid-containing nanoparticles are also being optimized and have been shown to significantly reduce inflammation in rat models of uveitis [ 103 ].…”