Development of Eudragit®-Coated Linezolid-Loaded Lipid Nanoparticles for Enhanced Ocular Delivery in Bacterial Keratitis Treatment

Abstract

Linezolid (LNZ), oxazolidinone antibiotic, is widely used in clinical practice for treatment of bacterial keratitis. Despite its efficacy, the application of LNZ in ophthalmic delivery is hindered by significant precorneal drug loss and poor ocular bioavailability. In this study, LNZ-loaded lipid nanoparticles, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), were developed using high-pressure homogenization technique. The formulations exhibited physicochemical properties within acceptable limits, and solid-state characterization revealed that LNZ was either molecularly dispersed or present in an amorphous state within the lipid matrix.

Highlights

LNZ-loaded NLC formulations exhibited superior corneal permeation through excised porcine corneas compared to their SLNs.

EU-coated LNZ-loaded lipid nanoparticles improved controlled drug release, mucoadhesion, and ocular cytocompatibility.

EU-modified NLCs exhibited comparable or superior efficacy against gram-positive bacteria compared to Zyvox®, a commercial linezolid product.

EU-coated LNZ-loaded NLCs remained stable for at least 3 months at 4 °C and 25 °C.

The surface of the lipid nanoparticles was modified using Eudragit® RL 100 (EU), a cationic polymer, and its effects were evaluated. The EU-coated formulations demonstrated particle sizes ranging from 144 to 158 nm, a polydispersity index below 0.25, zeta potentials between +17 and +20 mV, and high entrapment efficiencies ranging from 73% to 93%. The EU-coated LNZ-loaded SLNs and NLCs demonstrated controlled drug release, excellent mucoadhesive properties, low hemolytic activity, mild irritation, and ocular cytocompatibility.

Additionally, these formulations exhibited comparable or superior antibacterial efficacy against gram-positive bacteria relative to Zyvox®, a commercially available product. Notably, NLC formulations exhibited enhanced corneal permeation through excised porcine corneas and greater stability over at least 3 months of storage at 4 °C and 25 °C compared to SLNs. In summary, EU-modified LNZ-loaded NLCs show significant promise as a potential therapeutic strategy for ocular bacterial keratitis. However, further studies focusing on long-term stability and in vivo efficacy are required to support their clinical application.

Materials

Linezolid (LNZ, 99.7% purity) was purchased from KyongBo Pharmaceutical Co., Ltd (Seoul, Korea). Glyceryl behenate (Compritol® 888 ATO), glyceryl palmitostearate (Precirol® ATO 5), Labrafac ™ Lipophile WL 1349, Labrafil® M1944 CS, Labrasol® and Plurol® oleique were kindly donated by Gattefossé, (Saint-Priest, France). Glyceryl tristearate (Dynasan® 118) was kindly gifted by Sasol Germany GmbH (Hamburg, Germany). Almond oil was purchased from H.E. Daniel Ltd. (Tunbridge Wells, UK), castor oil.

Theingi Tun, Hay Marn Hnin, Pawina Kanchanasin, Wongsakorn Phongsopitanun, Nonthaneth Nalinratana, Phatsawee Jansook, Development of Eudragit®-Coated Linezolid-Loaded Lipid Nanoparticles for Enhanced Ocular Delivery in Bacterial Keratitis Treatment, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2025, 137210, ISSN 0927-7757, https://doi.org/10.1016/j.colsurfa.2025.137210.