Non-mulberry Silk Fibroin Biomaterial for Corneal Regeneration.

PURPOSE: Successful repair of a damaged corneal surface is a great challenge and may require the use of a scaffold that supports cell growth and differentiation. Amniotic membrane is currently used for this purpose, in spite of its limitations. A thin transparent silk fibroin film from non-mulberry Antheraea mylitta (Am) has been developed which offers to be a promising alternative. The silk scaffolds provide sufficient rigidity for easy handling, the scaffolds support the sprouting, migration, attachment and growth of epithelial cells and keratocytes from rat corneal explants; the cells form a cell sheet, preserve their phenotypes, express cytokeratin3 and vimentin respectively. The films also support growth of limbal stem cell evidenced by expression of ABCG2. The cell growth on the silk film and the amniotic membrane is comparable. The implanted film within the rabbit cornea remains transparent, stable. The clinical examination as well as histology shows absence of any inflammatory response or neovascularization. The corneal surface integrity is maintained; tear formation, intraocular pressure and electroretinography of implanted eyes show no adverse changes. The silk fibroin film from non-mulberry silk worms may be a worthy candidate for use as a corneal scaffold.

Curcumin nanoparticles inhibit corneal neovascularization.

UNLABELLED: Corneal neovascularization is a leading cause for compromised vision. Therapeutic prevention of corneal neovascularization is a major clinical challenge, and there is a compelling need to seek effective and safe therapy for this pathology. This study is aimed to evaluate curcumin nanoparticle for prevention of corneal neovascularization. MePEG-PCL nanoparticles were successfully prepared and characterized. The nanoparticle of curcumin has shown increased efficiency in preventing angiogenic sprouting in vitro. Topical delivery of curcumin nanoparticle in the eye showed enhanced retention of curcumin in the cornea, and significant improvement in prevention of corneal neovascularization over free curcumin as graded clinically and by histopathology; suppression in the expression of VEGF, inflammatory cytokines, and MMP was evidenced in the treated cornea. Curcumin inhibited NFκB in LPS-induced corneal cells. Histopathology and scanning electron microscopy showed absence of any adverse change in the corneal structure following application of curcumin nanoparticle. Therefore, we conclude that curcumin nanoparticle can be a potential candidate for prevention of corneal neovascularization. KEY MESSAGE: • Curcumin nanoparticles show enhanced retention of curcumin in the cornea. • Curcumin NPs suppress the expression of VEGF, inflammatory cytokines, and MMP. • Curcumin NPs prevent corneal neovascularization by suppressing the NFκB pathway. • Curcumin NPs may be a promising candidate for prevention of corneal neovascularization.

Pirfenidone nanoparticles improve corneal wound healing and prevent scarring following alkali burn.

PURPOSE: To evaluate the effects of pirfenidone nanoparticles on corneal re-epithelialization and scarring, major clinical challenges after alkali burn. METHODS: Effect of pirfenidone on collagen I and α-smooth muscle actin (α-SMA) synthesis by TGFß induced primary corneal fibroblast cells was evaluated by immunoblotting and immunocytochemistry. Pirfenidone loaded poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared, characterized and their cellular entry was examined in primary corneal fibroblast cells by fluorescence microscopy. Alkali burn was induced in one eye of Sprague Dawley rats followed by daily topical treatment with free pirfenidone, pirfenidone nanoparticles or vehicle. Corneal re-epithelialization was assessed daily by flourescein dye test; absence of stained area indicated complete re-epithelialization and the time for complete re-epithelialization was determined. Corneal haze was assessed daily for 7 days under slit lamp microscope and graded using a standard method. After 7 days, collagen I deposition in the superficial layer of cornea was examined by immunohistochemistry. RESULTS: Pirfenidone prevented (P<0.05) increase in TGF ß induced collagen I and α-SMA synthesis by corneal fibroblasts in a dose dependent manner. Pirfenidone could be loaded successfully within PLGA nanoparticles, which entered the corneal fibroblasts within 5 minutes. Pirfenidone nanoparticles but not free pirfenidone significantly (P<0.05) reduced collagen I level, corneal haze and the time for corneal re-epithelialization following alkali burn. CONCLUSION: Pirfenidone decreases collagen synthesis and prevents myofibroblast formation. Pirfenidone nanoparticles improve corneal wound healing and prevent fibrosis. Pirfenidone nanoparticles are of potential value in treating corneal chemical burns and other corneal fibrotic diseases.

Doxorubicin-loaded MePEG-PCL nanoparticles for prevention of posterior capsular opacification.

AIMS: Cytotoxic drugs are considered as potent candidates for the prevention of posterior capsular opacification (PCO), but the toxicity incited to healthy intraocular structures is a major concern. In this study, the authors evaluated the effect of PEG methyl ether-block-poly(ε-caprolactone) (MePEG-PCL) doxorubicin (DOX)-loaded nanoparticles (NPs) for prevention of PCO and their influence on intraocular tissues. METHODS: MePEG-PCL DOX NPs were prepared and characterized. The cytotoxic effect of DOX NPs on lens epithelial cells was compared with free drug. Its effect on PCO prevention following single subconjunctival delivery to lensectomized rabbits was assessed. Toxicity to intraocular structures was evaluated by specular microscopy, electroretinography and histopathology. The availability of DOX in aqueous humor was determined by HPLC. RESULTS: The cytotoxic effect of DOX NPs was higher compared with free DOX due to prolonged retention within the cells. A significant reduction in degree of PCO was observed in DOX NP-treated eyes compared with untreated controls. There was no significant change in the density and morphology of corneal endothelial cells or the histology of intraocular structures. Electroretinographs of treated eyes did not change compared with the pretreatment values. DOX could be detected by HPLC in the aqueous humor up to 48 h following single subconjunctival injection. CONCLUSION: The authors conclude that DOX-loaded MePEG-PCL NPs show promise as a new approach to selectively kill highly proliferative lens epithelial cells in vivo following cataract surgery, while sparing normal tissue.