Cytocompatibility, membrane disruption, and siRNA delivery using environmentally responsive cationic nanogels.

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 pKa, 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.

Control of Cationic Nanogel PEGylation in Heterogeneous ARGET ATRP Emulsion Polymerization with PEG Macromonomers.

Crosslinked cationic nanoscale networks with hydrophobic cores are an environmentally robust alternative to self-assembled polymeric drug delivery carriers with respect to therapeutic encapsulation and stability to dilution. However, the ability to tune the degree of PEG incorporated into nanogels during synthesis is more challenging. In this work, biodegradable cationic nanogels were synthesized by ARGET ATRP emulsion polymerization in a single step. The density of PEG in the final nanogels ranged from zero to 40 wt % and was dependent on the feed concentration of PEG monomer, surfactant concentration, surfactant hydrophilic-lipophilic balance, and the ratio of cationic to nonionic surfactant. A comprehensive analysis of nanogel material properties as a function of PEG graft density is presented including analysis of composition, monomer conversion, thermal properties, size, surface charge, and degradation. This study provides a robust analysis for the synthesis of degradable cationic nanogels via a controlled radical polymerization with predictable degrees of PEGylation.