Abstract
Lipid-like nanoparticles (LLNPs) have been shown to be an effective encapsulation and delivery tool for therapeutic molecules. While the preclinical development of lipid nanoparticle formulations has been of paramount importance, next-generation LLNPs present an opportunity of enhanced biocompatibility. With the change in amido functionality as part of the core backbone, our target, carbamate functionality within the LLNP core scaffold, was realized upon reaction of a protected amino alcohol onto the isocyanate generated in situ via a Curtius rearrangement. The single-step assembly of carbamate functionality starting from cyclohexane carboxylic acid in the presence of diphenylphosphoryl azide (DPPA) exceeds the metrics set forth for the rapid installment and enhanced biodegradability of next-generation lipid-like nanoparticles.
Published Version
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