Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma

Juan Li,1 Shuangyan Tian,1 Qi Tao,2 Yawen Zhao,1 Ruyi Gui,1 Fan Yang,1 Lingquan Zang,3 Yanzhong Chen,4 Qineng Ping,5 Dongzhi Hou1 1Department of Pharmaceutics, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People&...

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Autores principales:	Li J, Tian S, Tao Q, Zhao Y, Gui R, Yang F, Zang L, Chen Y, Ping Q, Hou D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Montmorillonite Glaucoma Chitosan Betaxolol hydrochloride；Preocular retention Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b4ee526c32ef41b58fc207f52830a218
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spelling	oai:doaj.org-article:b4ee526c32ef41b58fc207f52830a2182021-12-02T07:11:42ZMontmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma1178-2013https://doaj.org/article/b4ee526c32ef41b58fc207f52830a2182018-07-01T00:00:00Zhttps://www.dovepress.com/montmorillonitechitosan-nanoparticles-as-a-novel-controlled-release-to-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Juan Li,1 Shuangyan Tian,1 Qi Tao,2 Yawen Zhao,1 Ruyi Gui,1 Fan Yang,1 Lingquan Zang,3 Yanzhong Chen,4 Qineng Ping,5 Dongzhi Hou1 1Department of Pharmaceutics, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2CAS Key Laboratory of Mineralogy and Metallogeny & Guangdong Provincial Key Laboratory of Mineral Physics and Materials, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, People’s Republic of China; 3Department of Pharmacology, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 5College of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Background: To date, the rapid clearance from ocular surface has been a huge obstacle for using eye drops to treat glaucoma, since it has led to the short preocular residence time and low bioavailability. Methods: The novel nanoparticles (NPs) were designed for topical ophthalmic controlled drug delivery system through intercalating the BH into the interlayer gallery of Na-montmorillonite (Na+Mt) and then further enchasing chitosan nanoparticles. The resulting nanoparticles had a positive charge (+29±0.18 mV) with an average diameter of 460±0.6 nm. Results: In vitro study of drug release profiles suggested controlled release pattern. The irritation experiment analysis on both human immortalized cornea epithelial cell (iHCEC) and chorioallantoic membrane-trypan blue staining (CAM-TBS) showed good tolerance for ocular tissues. It was interestingly found that the nanoparticles could enter into iHCEC from the result of cellular uptake experiment measured by confocal layer scan microscopy (CLSM). Meanwhile, multilayered iHCEC was used to simulate the barrier of corneal epithelial cells for in vivo preocular retention capacity study, which suggested that BH-Mt/CS NPs could prolong the retention time in comparison with BH solution. The ocular pharmacokinetics studied by microdialysis sampling technique showed that AUC0-t and MRT0-t of BH-Mt/CS NPs were 1.99-fold and 1.75-fold higher than those of BH solution, indicating higher bioavailability. Moreover, the study of blood drug concentration, few researchers have reported, showed that low level drug could enter into blood, suggesting lower systematic side effect. Importantly, pharmacodynamics studies suggested that BH-Mt/CS NPs could make a significant decreased intraocular pressure on glaucomatous rabbits. Conclusion: Inspired by these advance of montmorillonite/chitosan nanoparticles, we envision that the BH-Mt/CS NPs will be a potential carrier for BH, opening up the possible applications in glaucoma therapy. Keywords: montmorillonite, glaucoma, chitosan, betaxolol hydrochloride, preocular retentionLi JTian STao QZhao YGui RYang FZang LChen YPing QHou DDove Medical PressarticleMontmorilloniteGlaucomaChitosanBetaxolol hydrochloride；Preocular retentionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3975-3987 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Montmorillonite Glaucoma Chitosan Betaxolol hydrochloride；Preocular retention Medicine (General) R5-920
spellingShingle	Montmorillonite Glaucoma Chitosan Betaxolol hydrochloride；Preocular retention Medicine (General) R5-920 Li J Tian S Tao Q Zhao Y Gui R Yang F Zang L Chen Y Ping Q Hou D Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
description	Juan Li,1 Shuangyan Tian,1 Qi Tao,2 Yawen Zhao,1 Ruyi Gui,1 Fan Yang,1 Lingquan Zang,3 Yanzhong Chen,4 Qineng Ping,5 Dongzhi Hou1 1Department of Pharmaceutics, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2CAS Key Laboratory of Mineralogy and Metallogeny & Guangdong Provincial Key Laboratory of Mineral Physics and Materials, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, People’s Republic of China; 3Department of Pharmacology, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 5College of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Background: To date, the rapid clearance from ocular surface has been a huge obstacle for using eye drops to treat glaucoma, since it has led to the short preocular residence time and low bioavailability. Methods: The novel nanoparticles (NPs) were designed for topical ophthalmic controlled drug delivery system through intercalating the BH into the interlayer gallery of Na-montmorillonite (Na+Mt) and then further enchasing chitosan nanoparticles. The resulting nanoparticles had a positive charge (+29±0.18 mV) with an average diameter of 460±0.6 nm. Results: In vitro study of drug release profiles suggested controlled release pattern. The irritation experiment analysis on both human immortalized cornea epithelial cell (iHCEC) and chorioallantoic membrane-trypan blue staining (CAM-TBS) showed good tolerance for ocular tissues. It was interestingly found that the nanoparticles could enter into iHCEC from the result of cellular uptake experiment measured by confocal layer scan microscopy (CLSM). Meanwhile, multilayered iHCEC was used to simulate the barrier of corneal epithelial cells for in vivo preocular retention capacity study, which suggested that BH-Mt/CS NPs could prolong the retention time in comparison with BH solution. The ocular pharmacokinetics studied by microdialysis sampling technique showed that AUC0-t and MRT0-t of BH-Mt/CS NPs were 1.99-fold and 1.75-fold higher than those of BH solution, indicating higher bioavailability. Moreover, the study of blood drug concentration, few researchers have reported, showed that low level drug could enter into blood, suggesting lower systematic side effect. Importantly, pharmacodynamics studies suggested that BH-Mt/CS NPs could make a significant decreased intraocular pressure on glaucomatous rabbits. Conclusion: Inspired by these advance of montmorillonite/chitosan nanoparticles, we envision that the BH-Mt/CS NPs will be a potential carrier for BH, opening up the possible applications in glaucoma therapy. Keywords: montmorillonite, glaucoma, chitosan, betaxolol hydrochloride, preocular retention
format	article
author	Li J Tian S Tao Q Zhao Y Gui R Yang F Zang L Chen Y Ping Q Hou D
author_facet	Li J Tian S Tao Q Zhao Y Gui R Yang F Zang L Chen Y Ping Q Hou D
author_sort	Li J
title	Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
title_short	Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
title_full	Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
title_fullStr	Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
title_full_unstemmed	Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
title_sort	montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/b4ee526c32ef41b58fc207f52830a218
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Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma

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