Biosafety and Efficacy Studies of Colchicine-Encapsulated Liposomes for Ocular Inflammatory Diseases.

Abstract

Inflammation is a critical component in the progression of various ocular diseases, such as age-related macular degeneration, diabetic retinopathy, and uveitis, leading to significant vision loss. Colchicine has been used for treating gout with its anti-inflammatory effect. However, free colchicine demonstrated cytotoxicity to ocular cells and cannot directly be used for eye disease. Thus, this study introduces, for the first time, the development and use of colchicine-encapsulated liposomes as a novel therapeutic approach for managing inflammation-driven ocular conditions. The encapsulation of colchicine within liposomes represents a significant innovation, aimed at enhancing biocompatibility and therapeutic efficacy while minimizing cytotoxic effects associated with free colchicine. Our research synthesized colchicine-loaded liposomes and assessed their therapeutic impact on human monocytes, macrophages, and retinal pigment epithelium (RPE) cells in an inflammatory environment. The findings reveal a groundbreaking improvement in treatment strategies, with a substantial reduction in TNF-alpha-induced reactive oxygen species (ROS) and nitric oxide (NO) production in RPE cells. Moreover, the colchicine-loaded liposomes significantly inhibited the proliferation and ROS production in activated monocytes and macrophages and effectively decreased interleukin (IL)-1β and IL-6 secretion, highlighting their strong anti-inflammatory properties and showed slightly better suppression of these two cytokines than dexamethasone-liposomes.