We report a family of monomers that are built from renewable resources and use the elimination of small molecules to access aliphatic polyesters, circumventing challenging monomer syntheses to make these functionalism polymers.

Eliminating small molecules from dioxolane rings affords isotactic poly(mandelic acid), with competing chain transfer overcome through dynamic vacuum polymerisation.

Polymeric nanoparticles (NPs) are attractive candidates for the controlled and targeted delivery of therapeutics in vitro and in vivo. However, detailed understanding of the uptake, location, and ultimate cellular fate of the NPs is necessary to satisfy safety concerns, which is difficult because of the nanoscale size of these carriers. In this work, we show how small chemical labels can be appended to poly(lactic acid-co-glycolic acid) (PLGA) to synthesize NPs that can then be imaged by stimulated Raman scattering microscopy, a vibrational imaging technique that can elucidate bond-specific information in biological environments, such as the identification of alkyne signatures in modified PLGA terpolymers. We show that both deuterium and alkyne labeled NPs can be imaged within primary rat microglia, and the alkyne NPs can also be imaged in ex vivo cortical mouse brain tissue. Immunohistochemical analysis confirms that the NPs localize in microglia in the mouse brain tissue, demonstrating that these NPs have the potential to deliver therapeutics selectively to microglia.

Novel vaccine platforms for delivery of nucleic acids based on viral and non-viral vectors, such as recombinant adeno associated viruses (rAAV) and lipid-based nanoparticles (LNPs), hold great promise. However, they pose significant manufacturing and analytical challenges due to their intrinsic structural complexity. During product development and process control, their design, characterization, and quality control require the combination of fit-for-purpose complementary analytical tools. Moreover, an in-depth methodological expertise and holistic approach to data analysis are required for robust measurements and to enable an adequate interpretation of experimental findings. Here the combination of complementary label-free biophysical techniques, including dynamic light scattering (DLS), multiangle-DLS (MADLS), Electrophoretic Light Scattering (ELS), nanoparticle tracking analysis (NTA), multiple detection SEC and differential scanning calorimetry (DSC), have been successfully used for the characterization of physical and chemical attributes of rAAV and LNPs encapsulating mRNA. Methods’ performance, applicability, dynamic range of detection and method optimization are discussed for the measurements of multiple critical physical−chemical quality attributes, including particle size distribution, aggregation propensity, polydispersity, particle concentration, particle structural properties and nucleic acid payload.

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