Alginate-functionalized nanoceria as ion-responsive eye drop formulation to treat corneal abrasion

Tzong-Yun Ger; Chia-Jung Yang; Hoang Linh Bui; Shingjiang Jessie Lue; Chun-Hsu Yao; Jui-Yang Lai

doi:10.1016/j.carbpol.2024.123164

Alginate-functionalized nanoceria as ion-responsive eye drop formulation to treat corneal abrasion

Carbohydr Polym. 2025 Mar 15:352:123164. doi: 10.1016/j.carbpol.2024.123164. Epub 2024 Dec 17.

Authors

Tzong-Yun Ger¹, Chia-Jung Yang², Hoang Linh Bui², Shingjiang Jessie Lue³, Chun-Hsu Yao⁴, Jui-Yang Lai⁵

Affiliations

¹ Department of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
² Department of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan.
³ Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 33302, Taiwan; Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Keelung 20401, Taiwan; Department of Safety, Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan.
⁴ Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40202, Taiwan; School of Chinese Medicine, China Medical University, Taichung 40202, Taiwan; Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan. Electronic address: chyao@mail.cmu.edu.tw.
⁵ Department of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan; Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan; Center for Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: jylai@mail.cgu.edu.tw.

PMID: 39843069
DOI: 10.1016/j.carbpol.2024.123164

Abstract

In this study, we aimed to develop ion-responsive and biocompatible alginate-capped nanoceria (Ce-ALG) for β-1,3-glucan (i.e., wound healing agent) delivery and corneal abrasion (CA) treatment. Specifically, alginate coatings confer the metallic nanocarriers with enhanced mucoadhesion, prolonged precorneal retention via hydrogen bonding, and improved viscosity. Additionally, increasing alginate grafting amount increased the surface stiffness and facilitated cellular uptake, thereby increasing bioactive potential of the nanocarriers. On the other hand, a stable egg-box structure formed by alginate complexation with Ca²⁺ not only heightened the encapsulation efficiency of β-1,3-glucan, but also provided sustained drug release during ion exchange with Na⁺ in tears. In vitro studies demonstrated an improvement in pharmacological wound closure, as evidenced by the accelerated migration and proliferation of corneal epithelial cells exposed to β-1,3-glucan-loaded Ce-ALG. In a rabbit model of CA, a single dose of the eye drop formulation with the maximum grafting amount of alginate remarkably reduced epithelial injury area by ~99 % at 5 days post-instillation, which was 45- and 53-fold more effective in wound area reduction than that of Ce and ketorolac (an analgesic commonly used for managing CA) groups, respectively. Overall, surface functionalization with alginate greatly enhanced the ocular bioavailability of nanotherapeutics for corneal epithelial injury recovery.

Keywords: Alginate; Corneal abrasion; Nanoceria; Ocular bioavailability; β-1,3-glucan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alginates* / chemistry
Animals
Cerium* / chemistry
Cornea / drug effects
Corneal Injuries* / drug therapy
Corneal Injuries* / pathology
Drug Carriers / chemistry
Drug Liberation
Ophthalmic Solutions* / chemistry
Ophthalmic Solutions* / pharmacology
Rabbits
Wound Healing / drug effects
beta-Glucans / administration & dosage
beta-Glucans / chemistry
beta-Glucans / pharmacology

Substances

Alginates
Ophthalmic Solutions
beta-Glucans
Cerium
beta-1,3-glucan
Drug Carriers