Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma
Authors Li J, Tian S, Tao Q, Zhao Y, Gui R, Yang F, Zang L, Chen Y, Ping Q, Hou D
Received 12 January 2018
Accepted for publication 8 May 2018
Published 10 July 2018 Volume 2018:13 Pages 3975—3987
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Farooq Shiekh
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
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
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