STAT6 siRNA Matrix-Loaded Gelatin Nanocarriers: Formulation, Characterization, and Ex Vivo Proof of Concept Using Adenocarcinoma Cells
STAT6 siRNA Matrix-Loaded Gelatin Nanocarriers: Formulation, Characterization, and Ex Vivo Proof of Concept Using Adenocarcinoma Cells
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STAT6 siRNA 基质负载明胶纳米载体：使用腺癌细胞的配方、表征和离体概念验证
DOI：
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发表时间：
2013
影响因子：
--
通讯作者：
M. Chougule
中科院分区：
文献类型：
--
作者：
Susanne R. Youngren;R. Tekade;B. Gustilo;P. Hoffmann;M. Chougule
siRNA治疗的临床应用由于细胞渗透性差、非特异性作用、快速降解和半衰期短而受到阻碍。因此，我们提出了通过将它们封装在明胶纳米载体（GNC）内来开发STAT 6 siRNA（S6 S）纳米载体剂的制剂。所制备的纳米制剂的大小，电荷，负载效率，释放动力学，稳定性，细胞毒性，和基因沉默测定进行了表征。还在不同pH值、血清水平和使用电泳测定的条件下评估了S6 S-GNC的稳定性。在MTT测定后，在人腺癌A549细胞中评价体外细胞毒性性能。开发的制剂的平均粒度、表面电荷和包封效率分别为70 ± 6.5 nm、+10 ± 1.5 mV和85 ± 4.0%。在缓冲溶液（pH 6.4至8.4）和FBS（10%v/v）存在下，S6 S-GNC显示出尺寸和电荷的不显著（P < 0.05）变化。使用未处理的细胞作为对照，用天然S6 S、S6 S-脂质体、安慰剂-GNC和S6 S-GNC处理A549细胞。观察到与天然S6 S（2.0 ± 0.55%）和S6 S-脂质体复合物（40 ± 3.1%）相比，S6 S-GNC使细胞活力显著降低55 ± 4.1%（P < 0.001）。这项研究推断，明胶聚合物为基础的纳米载体是一个强大的，稳定的，和生物相容性的战略，用于siRNA的交付。
The clinical utility of siRNA therapy has been hampered due to poor cell penetration, nonspecific effects, rapid degradation, and short half-life. We herewith proposed the formulation development of STAT6 siRNA (S6S) nanotherapeutic agent by encapsulating them within gelatin nanocarriers (GNC). The prepared nanoformulation was characterized for size, charge, loading efficiency, release kinetics, stability, cytotoxicity, and gene silencing assay. The stability of S6S-GNC was also assessed under conditions of varying pH, serum level, and using electrophoretic assays. In vitro cytotoxicity performance was evaluated in human adenocarcinoma A549 cells following MTT assay. The developed formulation resulted in an average particle size, surface charge, and encapsulation efficiency as 70 ± 6.5 nm, +10 ± 1.5 mV, and 85 ± 4.0%, respectively. S6S-GNC showed an insignificant (P < 0.05) change in the size and charge in the presence of buffer solutions (pH 6.4 to 8.4) and FBS (10% v/v). A549 cells were treated with native S6S, S6S-lipofectamine, placebo-GNC, and S6S-GNC using untreated cells as a control. It was observed that cell viability was decreased significantly with S6S-GNC by 55 ± 4.1% (P < 0.001) compared to native S6S (2.0 ± 0.55%) and S6S-lipofectamine complex (40 ± 3.1%). This investigation infers that gelatin polymer-based nanocarriers are a robust, stable, and biocompatible strategy for the delivery of siRNA.
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DOI：
10.1016/j.jconrel.2010.02.006
发表时间：
2010-06-01
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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作者：
Patlolla RR;Chougule M;Patel AR;Jackson T;Tata PN;Singh M
通讯作者：
Singh M
影响因子：
4
作者：
Randall D. Reif;Farzin Haque;Peixuan Guo
通讯作者：
Randall D. Reif;Farzin Haque;Peixuan Guo
影响因子：
5.8
作者：
Xu, Jing;Ganesh, Shanthi;Amiji, Mansoor
通讯作者：
Amiji, Mansoor
影响因子：
5.3
作者：
Chougule, Mahavir;Patel, Apurva R.;Sachdeva, Pratik;Jackson, Tanise;Singh, Mandip
通讯作者：
Singh, Mandip
影响因子：
4.2
作者：
Hoffmann, FuKun W.;Hashimoto, Ann C.;Hoffmann, Peter R.
通讯作者：
Hoffmann, Peter R.