Yi Huang,1 Qi Tao,2 Dongzhi Hou,1 Sheng Hu,1 Shuangyan Tian,1 Yanzhong Chen,3 Ruyi Gui,1 Lingling Yang,4 Yao Wang5 1College of Pharmacy, Guangdong Pharmaceutical University, 2Key Laboratory of Mineralogy and Metallogeny, Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Mineral Physics and Materials, 3Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, 4State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, 5Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China Abstract: As a novel ion-exchange carrier with high surface area and excellent exchangeability, montmorillonite (Mt) was intercalated with betaxolol hydrochloride (BH) to form a nanocomposite and then encapsulated by liposomes (Mt-BH-LPs) for an ophthalmic drug-delivery system. The Mt-BH and Mt-BH-LPs were prepared by an acidification process and ethanol injection combined with ammonium sulfate gradient methods. The successful formation of Mt-BH and Mt-BH-LPs was verified by thermogravimetric analysis, X-ray diffraction, Fourier-transform infrared spectra, and transmission electron microscopy. Mt-BH-LPs possessed the favorable physical characteristics of encapsulation efficiency, drug loading, mean particle size, and ζ-potential. In vitro release studies indicated Mt-BH-LPs effectively maintained a relatively sustained slow release. Immortalized human corneal epithelial cell cytotoxicity, in vivo rabbit eye-irritation tests, and chorioallantoic membrane–trypan blue staining all revealed that Mt-BH-LPs had no obvious irritation on ocular tissues. A new in vitro tear-turnover model, including inserts containing human corneal epithelial cells, was designed to evaluate the precorneal retention time of Mt-BH-LPs. The results showed that Mt-BH-LPs maintained a certain BH concentration in tear fluid for a longer period than the BH solution. In vivo precorneal retention studies also indicated Mt-BH-LPs prolonged drug retention on the ocular surface more than the BH solution. Furthermore, pharmacodynamic studies showed that Mt-BH-LPs had a prolonged effect on decreasing intraocular optical pressure in rabbits. Our results demonstrated that Mt-BH-LPs have potential as an ophthalmic delivery system. Keywords: liposome, montmorillonite, irritation, precorneal retention time, intraocular optical pressure
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