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

**Authors:** Xuehan Zhang, Qiuyun Shao, Mengjuan Yu, Yate Huang, Yuying Wang, Yangbing Wen, Kaihui Nan, Yangjun Chen

PMC · DOI: 10.1186/s12951-026-04141-7 · 2026-02-15

## TL;DR

Researchers developed a new type of eye drop using lignin-based nanoparticles to improve drug delivery for glaucoma treatment, showing better effectiveness and longer-lasting results.

## Contribution

A novel lignin-based nanoparticle formulation with mucoadhesive and corneal permeability-enhancing properties for improved glaucoma therapy.

## Key findings

- Lat@Lig-QCOS nanoparticles achieved a 2.2-fold increase in corneal permeability within 6 hours.
- The formulation reduced intraocular pressure by 5.2 mmHg, outperforming commercial Xalatan®.
- The nanocarrier showed excellent biocompatibility in in vitro and in vivo tests.

## 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.

The online version contains supplementary material available at 10.1186/s12951-026-04141-7.

## Linked entities

- **Chemicals:** latanoprost (PubChem CID 5311221), lignin (PubChem CID 175586)
- **Diseases:** glaucoma (MONDO:0005041)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ube2k (ubiquitin-conjugating enzyme E2K) [NCBI Gene 53323] {aka D5Ertd601e, E2-25k, HIP-2, Hip2, Hypg, Lig}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Tjp1 (tight junction protein 1) [NCBI Gene 21872] {aka ZO1}, Mog (myelin oligodendrocyte glycoprotein) [NCBI Gene 24558], Tjp1 (tight junction protein 1) [NCBI Gene 292994] {aka ZO-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, Ube2k (ubiquitin-conjugating enzyme E2K) [NCBI Gene 289623] {aka E2-25k, Hip2, Hypg, Lig}, Lat (linker for activation of T cells) [NCBI Gene 16797] {aka p36-38, pp36}
- **Diseases:** vision loss (MESH:D014786), optic neuropathy (MESH:D009901), inflammatory (MESH:D007249), hemolysis (MESH:D006461), blindness (MESH:D001766), open-angle glaucoma (MESH:D005902), hypotensive (MESH:D007022), IOP (MESH:D064090), cytotoxicity (MESH:D064420), retinal ganglion (MESH:D012173), fungal keratitis (MESH:D009181), multiple sclerosis (MESH:D009103), Glaucoma (MESH:D005901), ocular hypertension (MESH:D009798)
- **Chemicals:** streptomycin (MESH:D013307), acetonitrile (MESH:C032159), Triton X-100 (MESH:D017830), BX (MESH:D015784), EDTA (MESH:D004492), potassium dihydrogen phosphate (MESH:C013216), glycan (MESH:D011134), chitosan (MESH:D048271), NaCl (MESH:D012965), NaOH (MESH:D012972), hyaluronic acid (MESH:D006820), ethanol (MESH:D000431), prostaglandin F2alpha (MESH:D015237), VRC (MESH:D065819), acetic acid (MESH:D019342), Co6 (MESH:C517282), glutamate (MESH:D018698), resveratrol (MESH:D000077185), cerium oxide (MESH:C030583), CCK-8 (MESH:D012844), GTMAC (MESH:C045006), water (MESH:D014867), epoxy (MESH:D004853), oil (MESH:D009821), acetone (MESH:D000096), BM (MESH:D000068438), Kraft lignin (MESH:C076151), phosphoric acid (MESH:C030242), PBA (MESH:C075773), aspartate (MESH:D001224), Dex (MESH:D003907), Sodium fluorescein (MESH:D019793), penicillin (MESH:D010406), ZM241385 (MESH:C097270), sodium phosphate monobasic (MESH:C018279), doxorubicin (MESH:D004317), phenylboronic acid (MESH:C010686), H&amp;E (MESH:D006371), NaHCO3 (MESH:D017693), 1H (-), Lat (MESH:D000077338), periodic acid (MESH:D010504), trehalose (MESH:D014199), DAPI (MESH:C007293), hydrogen (MESH:D006859), camptothecin (MESH:D002166), cellulose (MESH:D002482), Dexamethasone phosphate (MESH:C004180), Tween 80 (MESH:D011136), PBS (MESH:D007854), THF (MESH:C018674), biopolymer (MESH:D001704), CO2 (MESH:D002245), steroid (MESH:D013256), cobalt (MESH:D003035), Lignin (MESH:D008031)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), HCECs — Rattus norvegicus (Rat), Transformed cell line (CVCL_6E32), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961861/full.md

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Source: https://tomesphere.com/paper/PMC12961861