LNP-encapsulated miRNA29b for corneal repair: A novel approach to combat fibrosis

Severe corneal injuries often result in corneal scarring, leading to visual impairment and corneal blindness. Currently, there is a lack of effective anti-corneal fibrosis drugs in clinical practice. MicroRNA-based therapies hold significant potential in combating fibrosis. However, the barrier function of the cornea and the fluid environment of the ocular surface reduce drug permeability and bioavailability, presenting significant challenges for local drug application. This study employs microfluidic technology to encapsulate miRNA29b in lipid nanoparticles (LNP) to create an LNP-miRNA29b delivery system (LNP-mir29b) for treating corneal mechanical injuries. <i>In vitro</i> experiments show that LNP-mir29b significantly inhibits the expression of α-smooth muscle actin (α-SMA) in an induced corneal stromal cell fibrosis model. <i>In vivo</i> experiments using rabbit corneal mechanical injury models indicate that LNP-mir29b effectively reduces fibrosis in the corneal stroma, promotes organized rearrangement of stromal collagen fibers, and decreases the expression of fibrosis-related genes, including Col1A2, Col3A1, Fn, and α-SMA. Additionally, LNP-mir29b accelerates the migration of corneal epithelial cells, promotes wound healing of the epithelium, restores the structural integrity of the corneal epithelium. The LNP system proposed in this study offers a novel approach with anti-fibrotic functionality, providing a new strategy for reducing scarring during the corneal injury repair process.