Formulation of Biocompatible Targeted ECO/siRNA Nanoparticles with Long-Term Stability for Clinical Translation of RNAi
| Autor: | Da Sun, Andrew L Schilb, Ryan C. W. Hall, Michelle Yin, Zheng-Rong Lu, Josef H Scheidt, X. Liu, Nadia Ayat, Zhanhu Sun, Amita M. Vaidya |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Biocompatibility Nanoparticle Biocompatible Materials Nanotechnology Biochemistry Polyethylene Glycols 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Study report RNA interference Cell Line Tumor parasitic diseases Drug Discovery PEG ratio Genetics Humans RNA Small Interfering Molecular Biology RNA Double-Stranded Chemistry technology industry and agriculture Translation (biology) Original Articles Biocompatible material 030104 developmental biology 030220 oncology & carcinogenesis Nanoparticles Molecular Medicine RNA Interference |
| Zdroj: | Nucleic Acid Ther |
| ISSN: | 2159-3345 2159-3337 |
| DOI: | 10.1089/nat.2019.0784 |
| Popis: | Nanoparticle based siRNA formulations often suffer from aggregation and loss of function during storage. We in this study report a frozen targeted RGD-polyethylene glycol (PEG)-ECO/siβ3 nanoparticle formulation with a prolonged shelf life and preserved nanoparticle functionality. The targeted RGD-PEG-ECO/siβ3 nanoparticles are formed by step-wised self-assembly of RGD-PEG-maleimide, ECO, and siRNA. The nanoparticles have a diameter of 224.5 ± 9.41 nm and a zeta potential to 45.96 ± 3.67 mV in water and a size of 234.34 ± 3.01 nm and a near neutral zeta potential in saline solution. The addition of sucrose does not affect their size and zeta potential and substantially preserves the integrity and biological activities of frozen and lyophilized formulations of the targeted nanoparticles. The frozen formulation with as low as 5% sucrose retains nanoparticle integrity (90% siRNA encapsulation), size distribution (polydispersity index [PDI] ≤20%), and functionality (at least 75% silencing efficiency) at -80°C for at least 1 year. The frozen RGD-PEG-ECO/siβ3 nanoparticle formulation exhibits excellent biocompatibility, with no adverse effects on hemocompatibility and minimal immunogenicity. As RNAi holds the promise in treating the previously untreatable diseases, the frozen nanoparticle formulation with the low sucrose concentration has the potential to be a delivery platform for clinical translation of RNAi therapeutics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|