Heating-driven self-assembled glycyrrhizin nanomicelles loading bisdemethoxycurcumin: Preparation, characterization, and efficacy evaluation on experimental dry eye

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2025-01, Vol.245, p.114206, Article 114206
• Main Authors: Yu, Linrong, Meng, Qingqian, Li, Mengshuang, Tian, Lei, Wu, Xianggen, Jie, Ying
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - administration & dosage; Antioxidants - chemistry; Antioxidants - pharmacology; Bisdemethoxycurcumin; Curcumin - administration & dosage; Curcumin - analogs & derivatives; Curcumin - chemistry; Curcumin - pharmacology; Diarylheptanoids - chemistry; Diarylheptanoids - pharmacology; Dry eye; Dry Eye Syndromes - drug therapy; Glycyrrhizic Acid - chemistry; Glycyrrhizic Acid - pharmacology; Glycyrrhizin; Heating-driven; Hot Temperature; Mice; Micelles; Nanoparticles - chemistry; Ophthalmic solution; Ophthalmic Solutions - chemistry; Ophthalmic Solutions - pharmacology; Particle Size
• ISSN: 0927-7765; 1873-4367; 1873-4367
• DOI: 10.1016/j.colsurfb.2024.114206

In this study, a simple but novel preparation method was developed by heating a mixture of dipotassium glycyrrhizinate (DG) and bisdemethoxycurcumin (BDMC) in aqueous solution, and a DG self-assembled nanomicelles-loading BDMC (named B@DNM) ophthalmic solution was successfully fabricated with this heating-driven process. AutoDock simulation analysis revealed that Pi-Alkyl hydrophobic interactions between BDMC and DG played important role in this self-assembled B@DNM. The optimized B@DNM, with a DG:BDMC mass ratio of 40:1 and heating time of 6 h, had a high encapsulation efficacy of 96.70 ± 0.13 % and particle sizes of 117.50 ± 6.07 nm. The apparent solubility of BDMC in B@DNM was significantly improved from bare BDMC (10.40 ± 0.16 μg/ml to 1405.60 ± 6.78 μg/ml) in artificial tears after 4 h incubation. B@DNM had great storage stability as an aqueous ophthalmic solution. B@DNM showed significantly improved in vitro antioxidant activity. Ex vivo hen’s egg test–chorioallantoic membrane assay and long-term in vivo mouse eye tolerance evaluation showed that B@DNM had good ocular safety profiles. B@DNM showed improved in vivo corneal permeation profiles in the mouse eyes. Topical administration of B@DNM achieved a significantly improved efficacy on a mouse model of dry eye disease (DED), including accelerating corneal wound healing, restoring corneal sensitivity, and inhibiting corneal neovascularization. Regulation of the high mobility group box 1 signal pathway was involved in B@DNM’s strong therapeutic effects. These findings demonstrate that heating is a simple method to prepare ocular nanoformulation with DG, and B@DNM might be a potential ocular drug for treating DED. •B@DNM ophthalmic solution was simply fabricated by a heating method.•The solubility of BDMC in B@DNM was significantly improved.•B@DNM demonstrated great ex vivo and in vivo safety profiles•B@DNM exhibited strong therapeutic potential against experimental dry eye.•Regulating HMGB1 signaling pathway was involved in this pharmacological activity.