Down regulation of inflammatory cytokines by the bioactive resveratrol-loaded chitoniosomes in induced ocular inflammation model

Abstract

Resveratrol (RSV); a natural polyphenol possess anti-inflammatory property through reduction of proinflammatory cytokines tumor-necrosis factor-alpha (TNFα) and interleukin (IL)-6 which play a key role in eye inflammation. Ocular inflammation results in irreversible tissues damage and impaired vision if left untreated. Surface coating of niosomes with chitosan can enhance their efficacy. Therefore the aim was to develop RSV-loaded chitosan-coated niosomes (Chitoniosomes) for topical ocular delivery. Chitoniosomes were formulated by ethanol-injection method. The selected formula (RSV.CsNiPolx) was composed of Span 60, Poloxamer407 and Cholesterol (3.5:3.5:3) coated with 0.6% w/v Chitosan. RSV.CsNiPolx showed particle size 363.1nm, PDI (0.21), zeta potential (+17.9), 90.3% entrapment efficiency, mucoadhesive efficiency with a sustained-release profile (56%) after 6 h. TEM showed circular shape niosomes surrounded by a relatively faded coat. The formula kept stable at 4 °C for 6 months storage. Good ocular tolerance of Chitoniosomes formulation without any inflammatory response to the rabbit eyes was confirmed by histological examination. Invivo antiinflammatory effects after 3 days treatment revealed reduced gene expressions of TNFα and IL-6, down to 49% and 55% respectively, in treated groups compared to control group. In conclusion, the results offer a promising nanoplatforms for topical application of the natural bioactive resveratrol in ocular inflammation.