Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

International Journal of Nanomedicine, Jan 2018

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier Shuangyan Tian,1 Juan Li,1 Qi Tao,2,3 Yawen Zhao,1 Zhufen Lv,4 Fan Yang,1 Haoyun Duan,5 Yanzhong Chen,4 Qingjun Zhou,5 Dongzhi Hou1 1Guangdong Engineering and Technology Research Center of Topical Precise Drug Delivery System, College of Pharmacy, Department of Pharmaceutics, Guangdong Pharmaceutical University, 2CAS Key Laboratory of Mineralogy and Metallogeny, 3Guangdong Provincial Key Laboratory of Mineral Physics and Materials, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, 4Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, 5State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China Background: Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods: To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion–solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Results: Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion: The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma. Keywords: glaucoma, montmorillonite, controlled release, betaxolol hydrochloride, preocular retention, microspheres

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Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

International Journal of Nanomedicine controlled drug delivery for glaucoma therapy using montmorillonite/eudragit microspheres as an ion-exchange carrier Juan li 2 Qi Tao 0 1 Yawen Zhao 2 Fan Yang 2 Qingjun Zhou 3 0 g uangdong Provincial Key laboratory of Mineral Physics and Materials, g uangzhou Institute of g eochemistry, c hinese a cademy of sciences 1 cas Key l aboratory of Mineralogy and Metallogeny 2 g uangdong engineering and Technology r esearch c enter of Topical Precise Drug Delivery system, c ollege of Pharmacy, Department of Pharmaceutics, g uangdong Pharmaceutical University 3 s tate Key l aboratory c ultivation Base, s handong Provincial Key laboratory of Ophthalmology, s handong eye Institute, s handong academy of Medical sciences , Qingdao, china 4 g uangdong Provincial Key l aboratory of a dvanced Drug Delivery s ystems, g uangdong Pharmaceutical University , guangzhou 8 1 0 2 - l u J - 3 1 n o 2 3 1 . 8 4 . 2 3 . 3 1 2 y b / m o c . s s e r p e v .do l.y fded roF PowerdbyTCPDF(ww.tcpdf.org) O r I g I N a l r e s e a r c h Zhufen lv 4 haoyun Duan 5 Yanzhong chen 4 Dongzhi hou 1 Background: Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods: To solve this, we successfully prepared novel controlled-release ionexchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion-solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Results: Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion: The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma. glaucoma; montmorillonite; controlled release; betaxolol hydrochloride; preocular - a o l n w o d e n i c i d e m o n a N f o l a n r u o J l a n o it a n r e t n I open access to scientific and medical research Introduction Glaucoma is a slowly progressive atrophy of the optic nerve, characterized by loss of peripheral visual function and an excavated appearance of the optic disc by ophthalmoscopy.1 It is commonly considered as the second leading cause of blindness and about 60.5 million individuals have been affected worldwide.2 High intraocular pressure (IOP) is the main risk factor, which leads to the degeneration of axons from the retinal ganglion cells. Therefore, many kinds of IOP lowering medications are used to manage the disease symptoms, such as timolol, betaxolol, epinephrine, pilocarpine, and dorzolamide.3 However, effective treatments are often limited owing to poor bioavailability of topically administered ocular drugs caused by a number of factors, including rapid tear turnover, transient residence time in the cul-de-sac, and washout of tear.4,5 These factors lead to rapid elimination of the drugs from the precorneal area. Thus, glaucoma therapy is still a significant challenge for clinical applications due to the absence of adequate drug concentration and short residence duration in the ocular tissues. In order to solve the problem, many significant efforts toward advanced ocular drug delivery systems 18 have been made over the last few decades. Thermosensitive l-u20 hydrogels, implants, and particulate carrier systems have been -J3 investigated to sustain the release of drug, prolong retention on1 time on the ocular surface, and improve bioavailability.6,7 .132 Among these strategies, particulate carrier systems have .48 gained considerable attention for ocular applications due to .233 their convenient application of liquid form, prolonged resiy21 dence time on the cornea, and low irritability.8 /bm Microspheres, as particulate carrier systems, are promis.sco ing drug delivery systems for eye application because of the (...truncated)


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Shuangyan Tian, Juan Li, Qi Tao, Yawen Zhao, Zhufen Lv, Fan Yang, Haoyun Duan, Yanzhong Chen, Qingjun Zhou, Dongzhi Hou. Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier, International Journal of Nanomedicine, 2018, pp. 415-428, DOI: 10.2147/IJN.S146346