Active trans-corneal drug delivery with ocular adhesive micelles for efficient glaucoma therapy

Qiuyu Wei; Chenchen Zhu; Guiping Yuan; Jiahui Jin; Jing Zhang; Wufa Fan; Ying Piao; Shiqun Shao; Sen Lin; Jiajia Xiang; Youqing Shen

doi:10.1016/j.jconrel.2024.11.050

Active trans-corneal drug delivery with ocular adhesive micelles for efficient glaucoma therapy

J Control Release. 2024 Nov 23:S0168-3659(24)00807-1. doi: 10.1016/j.jconrel.2024.11.050. Online ahead of print.

Authors

Qiuyu Wei¹, Chenchen Zhu², Guiping Yuan¹, Jiahui Jin³, Jing Zhang¹, Wufa Fan¹, Ying Piao¹, Shiqun Shao⁴, Sen Lin⁵, Jiajia Xiang⁶, Youqing Shen⁷

Affiliations

¹ Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biomass Chemical Engineering of the Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China.
² National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Department of Ophthalmology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233099, Anhui, China.
³ National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
⁴ Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biomass Chemical Engineering of the Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311215, China.
⁵ National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China. Electronic address: lin_sen@wmu.edu.cn.
⁶ Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biomass Chemical Engineering of the Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China. Electronic address: xiang_jj@zju.edu.cn.
⁷ Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biomass Chemical Engineering of the Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China. Electronic address: shenyq@zju.edu.cn.

PMID: 39586498
DOI: 10.1016/j.jconrel.2024.11.050

Abstract

Efficient and noninvasive drug delivery for glaucoma therapy necessitates prolonged retention on the ocular surface and deep penetration into the cornea. However, inherent physiological defenses such as rapid tear clearance and low cornea permeability present significant challenges that hinder the effectiveness of trans-corneal drug delivery. In this study, we demonstrate the potential of zwitterionic micelles composed of poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)-block-poly(ε-caprolactone) (OPDEA-PCL) amphiphiles as a biocompatible carrier for trans-corneal drug delivery. These micelles exhibit enhanced adhesion to ocular tissues and resistance to tear clearance due to their unique affinity for cell membranes. These characteristics facilitate adsorptive-mediated transcytosis, significantly augmenting trans-corneal transport and intraocular accumulation of the glaucoma medication brinzolamide (BRZ). As a result, OPDEA-PCL/BRZ formulations effectively normalize intraocular pressure in an open-angle glaucoma rat model, surpassing PEGylated and free BRZ formulations. This research underscores the potential utility of OPDEA-PCL micelles as a promising vehicle for noninvasive topical trans-corneal drug delivery in glaucoma therapy.

Keywords: Corneal barrier; Glaucoma therapy; Ocular drug delivery; Ocular surface retention; Trans-corneal delivery; Transcytosis.