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 AUC0-6 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.

Ophthalmic solution of organic-inorganic layered double hydroxides hybrid nanocomposites based on layered double hydroxides(LDH)intercalated with pirenoxine sodium(PRN)and chitosan-glutathione(CG)was prepared, characterized and evaluated using rabbit precorneal retention. Mg-Al-PRN-LDH, Zn-Al-PRN-LDH and CG-PRN-LDH were synthesized by co-precipitation. The nanocomposites were characterized by laser particle sizer, powder X-ray diffraction(X-RD), fourier transform infrared spectra(FTIR)and transmission electron micrographs(TEM). The release of PRN from Mg-Al-PRN-LDH, Zn-Al-PRN-LDH, and CG-PRN-LDH nanocomposites and API in artificial tear was compared. Based on in vivo precorneal retention studies, PRN-LDH and CG-PRN-LDH nanocomposite dispersions showed significantly higher AUC(3. 72-, 7. 59-folds)and MRT(2. 18-, 2. 60-folds)than that of the commercial eye drops group. Organic-inorganic layered double hydroxides hybrid nanocomposites CG-PRN-LDH dispersions could remarkably improve precorneal retention of PRN.