Cytocompatibility, Membrane Disruption, and siRNA Delivery using Environmentally Responsive Cationic Nanogels

Autor: David S. Spencer, Aaliyah B. Shodeinde, Hannah R. Hodges, David W. Beckman, Nicholas A. Peppas, Bryan C. Luu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: J Control Release
Popis: Advances in the formulation of nucleic acid-based therapeutics have rendered them a promising avenue for treating diverse ailments. Nonetheless, clinical translation of these therapies is hindered by a lack of strategies to ensure the delivery of these nucleic acids in a safe, efficacious manner with the required spatial and temporal control. To this aim, environmentally responsive hydrogels are of interest due to their ability to provide the desired characteristics of a protective carrier for siRNA delivery. Previous work in our laboratory has demonstrated the ability to synthesize nanoparticle formulations with targeted pK(a), swelling, and surface PEG density. Here, a library of nanoparticle formulations was assessed on their in vitro toxicity, hemolytic capacity, siRNA loading, and gene-silencing efficacy. Successful candidates exhibited the lowest degrees of cytotoxicity, pH-dependent membrane disruption potential, the highest siRNA loading, and the highest transfection efficacies.
Databáze: OpenAIRE