AAPS PharmSci

Factors influencing the choice of optimal individualized dosing strategies targeting a drug concentration or effect

Siv Jönsson

Katalin Matolcsi

Mats O. Karlsson

影响以药物浓度或效应为目标的最佳个体化给药策略选择因素

Small interfering RNA (siRNA) can induce RNA interference, which leads to the knockdown of messenger RNA (mRNA) and protein. As a result, siRNA is often used in vitro and in vivo to unravel the function of genes and as a therapeutic agent to disrupt excessive expression of disease-related genes. However, there is a large gap between in vitro and in vivo models in terms of simplicity, flexibility, throughput, and translatability. This gap could be bridged by using precision-cut tissue slices, which represent viable explants prepared from animal or human tissue that can be cultured ex vivo. Previously, we demonstrated that self-deliverable siRNA (Accell siRNA) induced significant mRNA knockdown in lung slices. The goal of this study, however, was to investigate whether Accell siRNA also induced protein knockdown in murine lung slices. Slices were incubated for up to 96 h with no siRNA (untransfected), non-targeting siRNA (control), or gene-targeting siRNA (Gapdh, Ppib, Serpinh1, and Bcl2l1). Overall, untransfected and transfected slices remained viable during an incubation of 96 h. In addition, gene-targeting siRNAs induced not only significant and specific mRNA knockdown but also protein knockdown. Finally, protein knockdown of fibrogenesis-related targets (Ppib, Serpinh1, and Bcl2l1) was shown to influence fibrogenesis on mRNA level, thereby demonstrating this model its utility in functional genomics and translational research.

Mitchel Ruigrok

Jia Ling Xian

H.W. Frijlink

Barbro Melgert

Wouter Hinrichs

Peter Olinga

siRNA-mediated protein knockdown in precision-cut lung slices

siRNA介导的精准切割肺切片中的蛋白质敲降

F. Selmin

S. Franzè

U. Musazzi

P. MInghetti

F. Cilurzo

Protecting Effect of Threalose and PVP in Freeze-Drying Liposomes Prepared by Ethanol Injection

乙醇注射法制备的脂质体中苏拉糖和PVP的保护作用

Valentyn Mohylyuk

Kavil Patel

Darragh Murnane

Craig Richardson

Fang Liu

Investigation into the internal structure of coated microparticles to support formulation and coating process development

研究涂层微粒内部结构以支持制剂与涂层工艺开发

Atif Madi

Jeremiah Kelleher

Gareth C. Gilvary

David Jones

Shu Li

Yiwei Tian

Ammar Almajaan

Zoe Senta Loys

Gavin Andrews

Anne-Marie Healy

Manufacture of a Fixed Dose Combination Product for the Treatment of Type II Diabetes by Hot Melt Continuous Granulation

通过热熔连续造粒法制备治疗2型糖尿病的固定剂量复方制剂

Jincheng Yang

The Effects of Differential Scanning Calorimetry Conditions on the Determined Solubility of Felodipine in Soluplus

差示扫描量热法条件对非洛地平在Soluplus中溶解度测定影响的研究

Effect of Preparation Method and Method Conditions on the Stability of High Drug-Loaded (60% w/w) Amorphous Solid Dispersion (ASD) of Felodipine-Soluplus®

制备方法及方法条件对高载药量（60% w/w）非洛地平-Soluplus®无定形固体分散体（ASD）稳定性的影响

差示扫描量热法条件对Soluplus中非洛地平溶解度测定影响的研究

制备方法及条件对高载药量（60% w/w）非洛地平-Soluplus®无定形固体分散体稳定性的影响

差示扫描量热法条件对Soluplus中非洛地平溶解度测定结果的影响

Publication Information	Publisher: American Association of Pharmaceutical Scientists，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1999，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

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Factors influencing the choice of optimal individualized dosing strategies targeting a drug concentration or effect

siRNA-mediated protein knockdown in precision-cut lung slices

Protecting Effect of Threalose and PVP in Freeze-Drying Liposomes Prepared by Ethanol Injection

Investigation into the internal structure of coated microparticles to support formulation and coating process development

Manufacture of a Fixed Dose Combination Product for the Treatment of Type II Diabetes by Hot Melt Continuous Granulation

The Effects of Differential Scanning Calorimetry Conditions on the Determined Solubility of Felodipine in Soluplus

Effect of Preparation Method and Method Conditions on the Stability of High Drug-Loaded (60% w/w) Amorphous Solid Dispersion (ASD) of Felodipine-Soluplus®

The Effects of Differential Scanning Calorimetry Conditions on the Determined Solubility of Felodipine in Soluplus

Effect of Preparation Method and Method Conditions on the Stability of High Drug-Loaded (60% w/w) Amorphous Solid Dispersion (ASD) of Felodipine-Soluplus®

The Effects of Differential Scanning Calorimetry Conditions on the Determined Solubility of Felodipine in Soluplus