Mucoadhesive and corneal permeable nano eye drops for improved anti-glaucoma therapy

Abstract Glaucoma, characterized by elevated intraocular pressure (IOP), is the leading cause of irreversible vision loss worldwide. While topical eye drops remain the standard for IOP control, ocular surface dynamic and static barriers significantly limit intraocular drug bioavailability. Enhancing corneal retention and permeability is therefore crucial for effective glaucoma therapy. Here, we developed lignin-based nanoparticles coated with quaternary ammonium chitosan oligosaccharide (Lig-QCOS) for encapsulating and delivering the lipophilic drug latanoprost (Lat), a first-line hypotensive agent. The resulting Lat@Lig-QCOS nanoparticles exhibited a hydrodynamic size of ~ 225.6 nm, a low polydispersity index of 0.08, and a positive Zeta potential of + 21.5 mV. The positively charged surface enables prolonged ocular mucoadhesion and concurrently modulates corneal epithelial tight junctions, enhancing paracellular permeation. This dual mechanism increased corneal permeability by 2.2-fold within 6 h, thereby promoting transcorneal drug transport. In a dexamethasone-induced mouse glaucoma model, a single topical dose of Lat@Lig-QCOS nanoparticles achieved a superior IOP reduction compared to free Lat and anionic Lat@Lig nanoparticles. The formulation produced a maximum IOP reduction of 5.2 mmHg, outperforming the commercial Xalatan ® (4.1 mmHg), and sustained efficacy for up to 10 h. The area under the pharmacodynamic response curve (AUC) of Lat@Lig-QCOS was 3.1-fold greater than that of free latanoprost, indicating markedly improved therapeutic performance. Comprehensive in vitro and in vivo biocompatibility assessments confirmed the excellent safety profile of the Lig-QCOS nanocarrier. Collectively, these findings highlight the potential of natural biopolymer-based nanosystems as efficient eye drop formulations for glaucoma treatment. Graphical Abstract