Ophthalmic solution of pirenoxine sodium-layered double hydroxide nanosheets and intercalated nanoparticles

The aim of this study was to evaluate the potential application of layered double hydroxide(LDH)nanosheets for ocular drug delivery. Using LDH nanosheets as carriers, carboxymethyl cellulose(CMC)as a stabilizer and pirenoxine sodium(PRN)as the model drug, CMC-PRN-LDH nanosheets were prepared. PRN-LDHs nanoparticles were synthesized via co-precipitation method. X-ray diffraction, atomic force microscopy, transmission electron microscopy and laser particle sizer were employed to characterize the physicochemical properties of LDH nanosheets, CMC-LDH nanosheets and PRN-LDH nanocomposites. Stability, accumulative release in vitro and precorneal retention in vivo of both CMC-PRN-LDH nanosheets and PRN-LDHs nanoparticles were evaluated. It was found that CMC-PRN-LDH nanosheets were electrostatically stabilized by CMC absorbed on the surface of LDH nanosheets, but PRN-LDHs nanoparticles aggregated in phosphate buffered saline. 12-hr accumulative release percentage of PRN from CMC-PRN-LDH nanosheets and PRN-LDHs nanoparticles were 70. 44% and 44. 21% in vitro, respectively. Compared with the commercial PRN eye drops, there existed 4. 18-fold increase in AUC_{0-6 h} and 1. 79-fold in mean retention time of CMC-PRN-LDH nanosheets. Negligible levels of PRN-LDHs nanoparticles might be attributed to inter-groups difference. Draize test showed that CMC-PRN-LDH nanosheets were non-irritant to the rabbit eyes after single and repeated dosing. It suggest that this novel LDH nanosheet could be a promising carrier for ocular drug delivery with prolonged residence time.