Abstract
Self-assembly of drug-polysacrrides conjugates forming nanostructures provides a simple and promising strategy for the extension of precorneal retention and enhancement of corneal permeability. In the present study, a series of dexamethasone-glycol chitosan (Dex-GCS) conjugates were synthesized and thoroughly characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and ultraviolet-visible (UV-Vis) spectroscopy. The resulting Dex-GCS conjugates were able to self-assemble into nanoparticles spontaneously with particle sizes in the range of 277-289 nm and a positive charge of approximately +15 mV. Roughly spherical nanoparticles were observed by transmission electron microscopy (TEM). The in vitro mucoadhesive properties of Dex-GCS nanoparticles were evaluated by recording the variations in the zeta potential after incubation with different concentrations of mucin. In vitro release studies performed in phosphate-buffered saline (PBS, pH = 7.4) indicated progressive Dex release up to 8 h, followed by a plateau up to 48 h. Dex-GCS nanoparticles caused slight cytotoxicity against L929, HCEC and RAW 264.7 cells after 24 h of incubation and displayed a nearly identical anti-inflammatory efficacy to dexamethasone sodium phosphate (Dexp) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. More importantly, the proposed Dex-GCS nanoparticles showed good ocular tolerance and provided a relatively longer precorneal duration compared with that of the aqueous solution formulation, which suggested that the self-assembled Dex-GCS nanoparticle might be a promising candidate for ophthalmic drug delivery.