Pentablock copolymer dexamethasone nanoformulations elevate MYOC: in vitro liberation, activity and safety in human trabecular meshwork cells
Pentablock copolymer dexamethasone nanoformulations elevate MYOC: in vitro liberation, activity and safety in human trabecular meshwork cells
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DOI：
10.2217/nnm-2017-0140
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发表时间：
2017-08-01
期刊：
影响因子：
5.5
通讯作者：
Mitra, Ashim K.
中科院分区：
文献类型：
--
作者：
Agrahari, Vibhuti;Li, Guorong;Mitra, Ashim K.
目的：本研究的目的是检测地塞米松（DEX）包封的五块共聚物纳米颗粒（np） （DEX-PB- np）长期治疗人小梁网（HTM）细胞时MYOC的升高。材料与方法：合成了PB共聚物和DEX-PB-NPs，并利用核磁共振、凝胶渗透色谱和x射线衍射分析对其进行了表征。western blot （WB）检测热媒细胞MYOC水平。结果：制备的DEX-PB-NPs的粒径范围为109 +/- 3.77 nm （n = 3）。三个多月后观察到NPs的长期DEX释放。使用pb -共聚物或DEX-PB-NPs治疗12周后，细胞活力和细胞毒性未受影响。5株HTM细胞株的WB数据显示，DEX-PB-NPs的存在使MYOC水平在4、8和12周分别提高了5.2 +/- 1.3、7.4 +/- 4.3和2.8 +/- 1.1倍，而对照组的MYOC水平分别为9.2 +/- 3.8、2.2 +/- 0.5和1.5 +/- 0.3倍（n = 5）。根据从对照井中提取DEX后MYOC水平的下降，DEX- pb - nps释放DEX至少10周。结论：本研究分析了DEX-PB-NPs对热媒细胞的作用。本文开发的体外细胞系统是一种有价值的工具，用于确定从聚合物np释放的类固醇的安全性和效果。
Aim: The aim of this study is to examine the elevation of MYOC in long-term treatment of human trabecular meshwork (HTM) cells using dexamethasone (DEX) encapsulated pentablock (PB) copolymer-based nanoparticles (NPs) (DEX-PB-NPs). Materials & methods: PB copolymers and DEX-PB-NPs were synthesized and characterized using nuclear magnetic resonance, gel permeation chromatography, and X-ray diffraction analyses. MYOC levels secreted from HTM cells were measured by western blot (WB) analysis. Results: DEX-PB-NPs were formulated in the size range of 109 +/- 3.77 nm (n = 3). A long term DEX release from the NPs was observed over three months. Cell viability and cytotoxicity were not affected up to 12 weeks of treatment with PB-copolymer or DEX-PB-NPs. WB data from five HTM cell strains showed that MYOC levels increased by 5.2 +/- 1.3, 7.4 +/- 4.3, and 2.8 +/- 1.1-fold in the presence of DEX-PB-NPs compared with 9.2 +/- 3.8, 2.2 +/- 0.5, and 1.5 +/- 0.3-fold at 4, 8 and 12 weeks in control-DEX treatment group, respectively (n = 5). Based on the decline in MYOC levels after withdrawal of DEX from control wells, DEX-PB-NPs released the DEX for at least 10 weeks. Conclusion: The treatment of HTM cells using DEX-PB-NPs were analyzed in this study. The in vitro cell-based system developed here is a valuable tool for determining the safety and effects of steroids released from polymeric NPs.