Polymeric nanocapsules: a potential new therapy for corneal wound healing

Abstract

Corneal injuries are one of the most frequently observed ocular diseases, leading to permanent damage and impaired vision if they are not treated properly. In this sense, adequate wound healing after injury is critical for keeping the integrity and structure of the cornea. The goal of this work was to assess the potential of polymeric nanocapsules, either unloaded or loaded with cyclosporine A or vitamin A, alone or in combination with mitomycin C, for the treatment of corneal injuries induced by photorefractive keratectomy surgery. The biopolymers selected for the formation of the nanocapsules were polyarginine and protamine, which are known for their penetration enhancement effect. The results showed that, following topical instillation to a mouse model of corneal injury, all the nanocapsule formulations, either unloaded or loaded with cyclosporine A or vitamin A, were able to stimulate corneal wound healing. In addition, the healing rate observed for the combination of unloaded protamine nanocapsules with mitomycin C was comparable to the one observed for the positive control Cacicol®, a biopolymer known as a corneal wound healing enhancer. Regarding the corneal opacity, the initial grade of corneal haze (>3) induced by the photorefractive keratectomy was more rapidly reduced in the case of the positive control, Cacicol®, than in corneas treated with the nanocapsules. In conclusion, this work shows that drug-free arginine-rich (polyarginine, protamine) nanocapsules exhibit a positive behavior with regard to their potential use for corneal wound healing.

Development and Optimization of Freeze-Dried Eye Drops Derived From Plasma Rich in Growth Factors Technology

“…Immunofluorescence assays were performed as described previously using antibodies to alpha-smooth muscle actin (α-SMA) (myofibroblast transformation; 1:200; Abcam) and Ki67 (proliferation marker; 1:500; Abcam). 26 , 27 , 30 , 31 Samples were incubated overnight with the corresponding antibody and revealed with an Alexa Fluor 594 anti-rabbit secondary antibody (1:500; Molecular Probes, Eugene, OR). To detect DNA fragmentation associated with apoptosis, terminal deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick-end labeling (TUNEL) was performed on frozen sections according to the manufacturer's instructions (Promega Corp., Madison, WI).…”

“…Surgical injury was performed using an Allegretto WaveLight excimer laser (PR-020407, Wavelight GmbH, Alcon, Erlangen, Germany) as previously described. [26][27][28][29][30] Right eyes were subjected to PRK surgery with a 2.0-mm ablation zone on the central cornea and a depth of 45 μm. The procedure included the simultaneous ablation of the epithelium (using a defined epithelial thickness profile of 25 μm centrally) and 20 μm of the anterior stroma (about 20% of the total stromal thickness) in a single step.…”

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy

“…[29][30][31] Right eyes were subjected to PRK surgery with the following parameters: a 1.5-mm 2 circular area, 45 lm of depth. The procedure included simultaneous ablation in a single step of the epithelium (using a defined epithelial thickness profile of 25 lm centrally) and 20 lm of the anterior stroma (representing approximately 20% of the total stromal thickness), removing all subbasal nerve fibers and intraepithelial terminals of the treated area.…”

Co-delivery of RNAi and chemokine by polyarginine nanocapsules enables the modulation of myeloid-derived suppressor cells

“…[39,40] In addition, polyarginine was chosen based on its transcytotic and endosomal scape abilities [41] that have been successfully employed by our research group to facilitate intracellular drug delivery. [42][43][44][45][46] These RNA-loaded NCs were provided with additional polyarginine and hyaluronic acid polymer layers in order to protect the RNA cargo and facilitate targeting. The NCs were extensively characterized in terms of their physicochemical properties and structural organization, as well as with regard to their macrophage chemoattractant capacity and ability to downregulate C/EBPβ splenic and tumor levels in a mouse model of fibrosarcoma.…”