Abstract
Synthetic nanoparticle-based drug delivery system is widely known for its ability to increase the efficacy and specificity of loaded drugs, but it often suffers from relatively higher immunotoxicity and higher costs as compared to traditional drug formulations. Contrarily, plant-derived nanoparticles appear to be free from these limitations of synthetic nanoparticles; they are naturally occurring biocompatible vesicles that do not generate immunotoxicity and are easy to obtain. Additionally, lipids isolated from plant-derived nanoparticles have shown the capability of assembling themselves to spherical nano-sized liposomal particles. Herein, we employ lipids extracted from ginger-derived nanoparticles and load them with therapeutic siRNA (CD98-siRNA) to create CD98-siRNA/ginger-lipid nanoparticles. Characterization of the CD98-siRNA/ginger-lipid nanoparticles showed that they present a spherical shape, with a diameter of around 189.5 nm. The surface zeta potential of the nanoparticles varies from -18.1 to -18.4 mV. Furthermore, in recent research, the CD98-siRNA/ginger-lipid nanoparticles have shown specific colon targeting capability and excellent anti-inflammatory efficacy in a Dextran Sodium Sulfate (DSS) induced mouse model of colitis.
Keywords: Ginger-derived nanoparticles, Thin-film hydration, siRNA delivery, Anti-inflammatory, Colon-targeted
Background
Small interference RNAs (siRNAs) are a type of promising therapeutic agents that can treat various diseases by silencing the abnormally upregulated messenger RNAs (mRNAs) (Nikam and Gore, 2018). Despite the effectiveness of siRNAs, the safe and efficient delivery of the siRNAs to the therapeutic targets is still a challenging task (Tatiparti et al., 2017). Studies have shown that artificially synthesized nanoparticles can be used to target low doses of siRNAs to specific colonic cell types (e.g., epithelial cells and macrophages) (Zhang et al., 2016b). However, artificially synthetic nanoparticles have several limitations, such as potential in vivo immune toxicity and formidable production cost. What is currently needed is a safer and more economical platform for siRNA-based drug delivery.Our laboratory and others have recently shown that plant-derived nanoparticles are capable of specifically target the colon, and these naturally occurring nanoparticles are safer and cheaper than synthetic nanoparticles (Zhang et al., 2016a). Additionally, we can extract lipids from these plant-derived nanoparticles and reassemble them to siRNA-incorporated nanoparticles, creating a colon-targeting siRNA/lipid nanoparticle (Zhang et al., 2017). In the following protocol, we will use ginger-derived nanoparticles and CD98-siRNA as starting materials to demonstrate the process of making CD98 siRNA nanoparticles (CD98-siRNA/ginger-lipid). The nanoparticles prepared in this protocol have shown its effectiveness in treating ulcerative colitis in recent research (Zhang et al., 2017).
Materials and Reagents
Equipment
Procedure
Data analysis
Notes
Recipes
Acknowledgments
This work was supported by the National Institute of Health of Diabetes and Digestive and Kidney (RO1-DK-071594 to D.M.). This work was adapted and modified from Zhang et al., 2017.
Competing interests
The authors declare no conflicts of interest.
Ethics
All the experiments conducted involving mice were approved by institutional animal care and use committee (IACUC) at Georgia State University (Atlanta, GA, USA).
References
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