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Targeted Delivery of LM22A-4 by Cubosomes Protects Retinal Ganglion Cells in an Experimental Glaucoma Model

37 Pages Posted: 26 Oct 2020 Publication Status: Published

See all articles by Yue Ding

Yue Ding

Department of Materials Science and Engineering, Monash University

Seong Hoong Chow

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University

Jinying Chen

Menzies Institute for Medical Research, University of Tasmania

Anton P. Le Brun

Australian Nuclear Science and Technology Organization (ANSTO)

Chun-Ming Wu

Australian Nuclear Science and Technology Organization (ANSTO)

Anthony P. Duff

Australian Nuclear Science and Technology Organization (ANSTO)

Yajun Wang

College of Chemistry & Materials Engineering, Wenzhou University

Vickie HY Wong

Department of Optometry and Vision Sciences, University of Melbourne

Da Zhao

Department of Optometry and Vision Sciences, University of Melbourne

Tzong-Hsien Lee

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University

Charlotte E. Conn

School of Science, College of Science, Engineering and Health, RMIT University

Hsien-Yi Hsu

School of Energy and Environment & Department of Materials Science and Engineering, City University of Hong Kong

Bang V. Bui

Department of Optometry and Vision Sciences, University of Melbourne

Guei-Sheung Liu

University of Tasmania - Menzies Institute for Medical Research

Hsin-Hui Shen

Monash University - Department of Materials Science and Engineering

Abstract

Glaucoma, a major cause of irreversible blindness worldwide, is associated with elevated intraocular pressure (IOP) and progressive loss of retinal ganglion cells (RGCs) that undergo apoptosis. A mechanism for RGCs injury involves impairment of neurotrophic support and exogenous supply of neurotrophic factors has been shown to be beneficial. However, neurotrophic factors can have widespread effects on neuronal tissues, thus targeting neurotrophic support to injured neurons may be a better neuroprotective strategy. In this study, we have encapsulated LM22A-4, a small neurotrophic factor mimetic, into Annexin V-conjugated cubosomes (L4-ACs) for targeted delivery to injured RGCs in a model of glaucoma, which is induced by acute IOP elevation. We have tested cubosomes formulations that encapsulate from 9% to 33% LM22A-4. Our data indicated that cubosomes encapsulating 9% and 17% LM22A-4 exhibited a mixture of Pn3m/Im3m cubic phase, whereas 23% and 33% showed a pure Im3m cubic phase. We found that 17% L4-ACs with Pn3m/Im3m symmetries showed better in-situ and in-vitro lipid membrane interactions than the 23% and 33% L4-ACs with Im3m symmetry. In vivo experiments showed that 17% L4-ACs targeted the posterior retina and the optic nerve head, which prevented RGCs loss in a mouse model of acute IOP elevation. These results provide evidence that cubosomes-based LM22A-4 delivery may be a useful targeted approached to prevent the progression of RGCs loss in glaucoma.

Keywords: Cubosomes, apoptosis, LM22A-4, SAXS, Neutron reflectometry, QCM-D, retinal ganglion cell, intraocular pressure and experimental glaucoma model

Suggested Citation

Ding, Yue and Chow, Seong Hoong and Chen, Jinying and Le Brun, Anton P. and Wu, Chun-Ming and Duff, Anthony P. and Wang, Yajun and Wong, Vickie HY and Zhao, Da and Lee, Tzong-Hsien and Conn, Charlotte E. and Hsu, Hsien-Yi and Bui, Bang V. and Liu, Guei-Sheung and Shen, Hsin-Hui, Targeted Delivery of LM22A-4 by Cubosomes Protects Retinal Ganglion Cells in an Experimental Glaucoma Model. Available at SSRN: https://ssrn.com/abstract=3718055 or http://dx.doi.org/10.2139/ssrn.3718055

Yue Ding

Department of Materials Science and Engineering, Monash University

Seong Hoong Chow

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University ( email )

Jinying Chen

Menzies Institute for Medical Research, University of Tasmania ( email )

Anton P. Le Brun

Australian Nuclear Science and Technology Organization (ANSTO) ( email )

Chun-Ming Wu

Australian Nuclear Science and Technology Organization (ANSTO) ( email )

Anthony P. Duff

Australian Nuclear Science and Technology Organization (ANSTO) ( email )

Yajun Wang

College of Chemistry & Materials Engineering, Wenzhou University

Vickie HY Wong

Department of Optometry and Vision Sciences, University of Melbourne ( email )

Da Zhao

Department of Optometry and Vision Sciences, University of Melbourne

Tzong-Hsien Lee

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University ( email )

Charlotte E. Conn

School of Science, College of Science, Engineering and Health, RMIT University ( email )

Hsien-Yi Hsu

School of Energy and Environment & Department of Materials Science and Engineering, City University of Hong Kong ( email )

Bang V. Bui

Department of Optometry and Vision Sciences, University of Melbourne ( email )

Guei-Sheung Liu

University of Tasmania - Menzies Institute for Medical Research ( email )

Australia

Hsin-Hui Shen (Contact Author)

Monash University - Department of Materials Science and Engineering ( email )

Victoria
Australia

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