Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery.
Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery.
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DOI：
10.2147/ijn.s148104
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发表时间：
2018
影响因子：
8
通讯作者：
Cao F
中科院分区：
文献类型：
--
作者：
Xu T;Xu X;Gu Y;Fang L;Cao F
为提高眼内生物利用度，传统的治疗策略主要是通过带正电荷的纳米载体、巯基化聚合物、吸收促进剂等来延长角膜前滞留时间和改善角膜通透性，而甘氨酰肌氨酸（Glycylsarcosine，GS）作为肽转运体-1（PepT-1）的活性靶配体，能特异性地与角膜表面的PepT-1相互作用，将纳米粒导向治疗部位。本研究的目的是探索基于壳聚糖-谷胱甘肽-甘氨酰肌氨酸（CG-GS）和层状双氢氧化物（LDH）的主动靶向插层纳米复合物作为治疗中后部疾病的新型载体。采用共沉淀-水热法制备了CG-GS-LDH插层纳米复合材料。在体兔角膜前滞留实验、离体荧光成像实验、体内分布实验和刺激性实验。在人角膜上皮原代细胞（HCEpiC）中研究了细胞毒性和细胞摄取。成功制备了CG-GS-LDH纳米复合材料，并通过FTIR和XRD对其进行了表征。兔实验表明，较长的角膜前滞留和较高的荧光探针/模型药物的分布。在体外细胞学研究中，CG-GS-LDH纳米复合物表现出比纯药物溶液更高的细胞摄取。此外，细胞摄取机制的研究表明，PepT-1的主动转运和网格蛋白介导的内吞作用都参与了CG-GS-LDH插层纳米复合材料的内化。眼刺激性研究和细胞毒性试验表明，这些纳米复合材料没有产生显着的刺激作用。活性靶向插层纳米复合材料具有延长药物在眼表滞留时间、提高药物透过角膜的能力，并能有效地将药物递送至靶点等优点，在眼局部给药方面具有巨大的潜力。
To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site.