Issue link: https://www.e-digitaleditions.com/i/1478917
www.biopharminternational.com Emerging Therapies 2022 eBook BioPharm International ® 25 Analytics vectors in gene therapy, antibody-drug conjugates, and antibody aggregation. The power of orthogonal approaches In the complex world of mRNA-based vaccines and ther- apies, tried and tested analytical technologies, such as DLS/MADLS, NTA, and ELS, are shining a light on the LNPs that help those medicines survive the journey from lab to factory to cellular site-of-action. Researchers are further augmenting those insights by evolving and ex- panding the applications of DSC and SEC–SLS to build further a more reliable picture of LNP attributes, improv- ing the chances for project success. Although individual biophysical characterization techniques provide valuable insights into the nature of LNPs, no single technology can provide a complete picture. Instead, orthogonal and complementary ap- proaches are needed to provide a more comprehensive understanding of the critical quality attributes that de- fine product quality, consistency, and, ultimately, effi- cacy (Table I). This prospect may be daunting if a company is unfa- miliar with some of these techniques. The broad exper- tise of an analytical partner can, therefore, help in the development of the applications needed to achieve a deeper understanding of LNPs. References 1. R. Kedmi, N. Ben-Arie, and D. Peer, Biomaterials 31 (26) 6867–6875 (2010). 2. R . Pat t ipei lu hu , e t a l., A dvanced Mate r ial s 3 4 , 2201095 (2022). 3. Malvern Panalytical, Developing an Analytical Work- f low for Nanomedicine and 3rd Generation Vaccine Pro- duction at Scale, Whitepaper (2022). 4. N. Markova, et al. Vaccines 10, 49 (2022). ■ FIGURE 3. Using size-exclusion chromatography–static light scattering (SEC–SLS) to show that the weight fraction (Wt fr) of messenger RNA (mRNA) within mRNA–lipid nanoparticles (LNPs) varies across both a single formulation and between different formulations: (a) mRNA–LNP1; (b) mRNA–LNP2 (4). RI is refractive index. TABLE I. Proven analytical technologies monitor a range of lipid nanoparticle attributes (4). DLS is dynamic light scattering. MADLS is multi-angle light scattering. NTA is nanoparticle tracking analysis. ELS is electrophoretic light scattering. SEC–SLS is size-exclusion chromatography–static light scattering. DSC is differential scanning calorimetry. Particle size Polydispersity Particle concentration Surface charge Thermal stability Higher-order structure Particle composition DLS ✓ ✓ ✓ MADLS ✓ ✓ ✓ NTA ✓ ✓ ✓ ELS ✓ SEC–SLS ✓ ✓ ✓ ✓ DSC ✓ ✓