Compritol solid lipid nanoparticle formulations enhance the protective effect of betulinic acid derivatives in human Müller cells against oxidative injury. (February 2022)

• Record Type: Journal Article
• Authors: Cheng, Zhengqi; Li, Yue; Wang, Ke; Zhu, Xue; Tharkar, Priyanka; Shu, Wenying; Zhang, Ting; Zeng, Shaoxue; Zhu, Ling; Murray, Michael; Chrzanowski, Wojciech; Zhou, Fanfan
• Is Part Of: Experimental eye research. Volume 215(2022)
• Publication Date: 2022-02
• Subjects: Solid lipid nanoparticle -- Betulinic acid -- Anti-Oxidative -- Retinal pigment epithelium -- Müller cells; BA betulinic acid -- DMEM Dulbecco's Modified Eagle Medium -- EE encapsulation efficiency -- FBS fetal bovine serum -- HD5 SLN Compritol HD5 ATO SLN -- PBS phosphate-buffered saline -- PI propidium iodide -- ROS reactive oxygen species -- SLNs solid lipid nanoparticles -- 888 SLN Compritol 888 ATO SLN; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2021.108906
• Languages: English
• ISSNs: 0014-4835

Abstract

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. Graphical abstract: Image 1 Highlights: Novel application of compritol nanoparticles in compound delivery in Müller cells. First attempt to encapsulate betulinic acid derivatives in compritol nanoparticles. Greatly enhanced protective effect on human Müller cells against oxidative stress.