Compritol solid lipid nanoparticle formulations enhance the protective effect of betulinic acid derivatives in human Müller cells against oxidative injury

Zhengqi Cheng; Yue Li; Ke Wang; Xue Zhu; Priyanka Tharkar; Wenying Shu; Ting Zhang; Shaoxue Zeng; Ling Zhu; Michael Murray; Wojciech Chrzanowski; Fanfan Zhou

doi:10.1016/j.exer.2021.108906

Compritol solid lipid nanoparticle formulations enhance the protective effect of betulinic acid derivatives in human Müller cells against oxidative injury

Exp Eye Res. 2022 Feb:215:108906. doi: 10.1016/j.exer.2021.108906. Epub 2021 Dec 23.

Authors

Zhengqi Cheng¹, Yue Li², Ke Wang³, Xue Zhu³, Priyanka Tharkar², Wenying Shu⁴, Ting Zhang⁵, Shaoxue Zeng⁶, Ling Zhu⁶, Michael Murray², Wojciech Chrzanowski⁷, Fanfan Zhou⁸

Affiliations

¹ Sydney Pharmacy School, The University of Sydney, NSW, 2006, Australia; Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China.
² Sydney Pharmacy School, The University of Sydney, NSW, 2006, Australia.
³ Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
⁴ Sydney Pharmacy School, The University of Sydney, NSW, 2006, Australia; Department of Pharmacy, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangdong Province, 511400, China.
⁵ Save Sight Institute, The University of Sydney, Sydney, NSW, 2000, Australia; State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
⁶ Save Sight Institute, The University of Sydney, Sydney, NSW, 2000, Australia.
⁷ Sydney Pharmacy School, The University of Sydney, NSW, 2006, Australia; The University of Sydney, Sydney Nano Institute, Camperdown, NSW, 2006, Australia.
⁸ Sydney Pharmacy School, The University of Sydney, NSW, 2006, Australia. Electronic address: Fanfan.zhou@sydney.edu.au.

PMID: 34953864
DOI: 10.1016/j.exer.2021.108906

Abstract

Müller cells maintain homeostatic functions in the retina. Their dysfunction leads to irreversible retinal diseases. Oxidative injury is a leading cause of retinal cytotoxicity. Our previous studies reported several betulinic acid (BA) derivatives can protect Müller cells from oxidative injury but achieving pharmacologically effective concentrations in the Müller cells could be a limitation. To optimise cellular delivery, we encapsulated the BA analogues H3, H5 and H7 into the clinically approved Compritol 888 and HD5 ATO solid lipid nanoparticles (SLNs) using the micro-emulsion method. The cytoprotective effects of these SLN-formulations were determined in human MIO-M1 cells. We found cytoprotection by H3 and H5 SLN-formulations was significantly enhanced, which was evident at concentrations much lower than those required with the free agents. Both SLN-formulations prolonged the duration of action of these agents. The most effective agent H5 delivered in 888 ATO SLNs attenuated glutamate-induced ROS formation and the associated necrosis in MIO-M1 cells. Overall, SLNs have emerged as promising delivery carriers for BA derivatives enhancing their protective effects against oxidative injury in human Müller cells. Our study is the first to show SLNs can be a viable route to delivery agents with improved efficacy and stability into human Müller cells favoring the treatment/prevention of retinal diseases.

Keywords: Anti-Oxidative; Betulinic acid; Müller cells; Retinal pigment epithelium; Solid lipid nanoparticle.

Publication types

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

MeSH terms

Betulinic Acid
Drug Carriers
Ependymoglial Cells
Humans
Liposomes
Nanoparticles*
Oxidative Stress
Pentacyclic Triterpenes
Retinal Diseases*

Substances

Drug Carriers
Lipid Nanoparticles
Liposomes
Pentacyclic Triterpenes
Betulinic Acid