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角膜内基因传递:基于固体脂质纳米粒载体的体外与离体评价。

Gene delivery in the cornea: in vitro & ex vivo evaluation of solid lipid nanoparticle-based vectors.

机构信息

Pharmacokinetic, Nanotechnology & Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, Spain.

Università degli Studi di Torino, Dipartimento di Scienza e Tecnologia del Farmaco, via Pietro Giuria 9, Turin, Italy.

出版信息

Nanomedicine (Lond). 2018 Aug 1;13(15):1847-1854. doi: 10.2217/nnm-2018-0112. Epub 2018 May 24.

Abstract

AIM

Inflammation is a process that underlies sight-threatening ocular surface diseases, and gene supplementation with the plasmid that encodes for p-IL10 will allow the sustained de novo synthesis of the cytokine to occur in corneal cells, and provide a long-term anti-inflammatory effect. This work describes the development of solid lipid nanoparticle systems for the delivery of p-IL10 to transfect the cornea.

RESULTS

In vitro, vectors showed suitable features as nonviral vectors (size, ζ-potential, DNA binding, protection and release), and they were able to enter and transfect human corneal epithelial cells. Ex vivo, the vectors were found to transfect the epithelium, the stroma and the endothelium in rabbit corneal explants. Distribution of gene expression within the cell layers of the cornea depended on the composition of the four vectors evaluated.

CONCLUSION

Solid lipid nanoparticle-based vectors are promising gene delivery systems for corneal diseases, including inflammation.

摘要

目的

炎症是一种潜在的致盲性眼表疾病,通过质粒 p-IL10 进行基因补充,可以使细胞持续从头合成细胞因子,从而产生长期的抗炎效果。本研究旨在开发用于将 p-IL10 递送至角膜的固体脂质纳米颗粒系统。

结果

体外实验表明,载体具有合适的非病毒载体特性(大小、ζ 电位、DNA 结合、保护和释放),并能够进入和转染人角膜上皮细胞。在兔角膜外植体中,载体可转染角膜上皮、基质和内皮。在角膜各层细胞中,基因表达的分布取决于所评估的四种载体的组成。

结论

基于固体脂质纳米颗粒的载体是治疗包括炎症在内的角膜疾病的有前途的基因传递系统。

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