Abstract
Cyclosporine A (CsA) is widely used to treat dry eye disease (DED), and ocular morbidity is on the rise and is a growing concern globally. However, several drug and formulation challenges, such as poor drug solubility, short pre-corneal residence time, and poor patient compliance, have limited the ocular bioavailability of CsA to in vitro drug release, ex vivo corneal permeation, and in vivo precorneal retention. Preclinical efficacy studies were performed to assess the efficacy of CsA-complex-loaded nano-reservoirs in an experimental dry-eye mouse model. Physicochemical characterization confirmed the formation of a stable complex and the improved solubility of CsA. In vitro release and ex vivo permeation studies indicated a controlled drug release and improved permeation, respectively. Furthermore, tear volume measurement and corneal damage assessment using slit-lamp imaging suggested decreased dry eye symptoms, significantly increasing tear volume in the drug-loaded nano-reservoir-treated group. Moreover, histopathological studies corroborated the tear volume and slit-lamp imaging results, with reduced inflammation and neovascularization. The poorly water-soluble drug with cyclodextrin complex incorporated nanoreservoir films presents a potential alternative for managing various ocular diseases. Graphical Abstract