title: A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride.
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.
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Mineralogy and Metallogeny, Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Mineral Physics and Materials.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tao
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University.
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Hou
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University.
authors.forename: Sheng
authors.initials: S
authors.lastname: Hu
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University.
authors.forename: Shuangyan
authors.initials: S
authors.lastname: Tian
authors.affiliation: Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Gui
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001546:Bentonite / Q000737:chemistry*; D015784:Betaxolol / Q000008:administration & dosage* / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D003315:Cornea / Q000187:drug effects; D003956:Dialysis; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005123:Eye / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005629:Frozen Sections; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007474:Ion Exchange; D008081:Liposomes; D053761:Nanocomposites / Q000737:chemistry; D010316:Particle Size; D011817:Rabbits; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D008081:Liposomes; D012996:Solutions; D001546:Bentonite; D015784:Betaxolol
keywords: intraocular optical pressure; irritation; liposome; montmorillonite; precorneal retention time