Ultra-small nanocomplexes based on polyvinylpyrrolidone K-17PF: A potential nanoplatform for the ocular delivery of kaempferol.

This study aims to create and evaluate a kaempferol (KAE) ophthalmic solution based on polyvinylpyrrolidone (PVP) nanocomplexes. KAE can be highly complexed with PVP K-17PF (17PF) to formulate an aqueous ophthalmic solution named 17PF-KAE. The optimized 17PF-KAE displays high complexing efficiency, an ultra-small size (8.628 ± 0.066 nm), and good aqueous dispersibility. 17PF-KAE did not show any obvious cytotoxicity or in vivo ocular tissue toxicity. Further, 17PF-KAE was observed to facilitate significant improvement in in vitro parallel artificial membrane permeability, in vitro cellular uptake, and ex vivo corneal permeation of KAE. Regarding the in vivo ocular absorption test, the KAE levels in the cornea and aqueous humor determined from the 17PF-KAE group were much higher than those in the free KAE solution group in addition to conjunctiva and the iris-ciliary body at certain time points. 17PF-KAE was also observed to promote remarkable improvement in in vitro antioxidant activity and in vivo anti-inflammatory activity. Moreover, a topical 17PF-KAE solution in mice eyes showed significant improvement in the treatment efficacy of corneal alkali burns over the free KAE solution. The therapeutic mechanism was also associated with inhibiting the production of key mediators of inflammation (CD54, IL-6, and TGF-β1) and angiogenic factors (VEGF). Therefore, these results demonstrate that 17PF-KAE may be a promising new ophthalmic formulation for the prophylaxis and treatment of oxidative stress and inflammation-related ocular diseases.