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22 BioPharm International ® Emerging Therapies 2022 eBook www.biopharminternational.com T he importance of messenger RNA (mRNA)- based vaccines and therapies in global healthcare is growing, spurred on by the success of Moderna's Spikevax and Pfizer– BioNTech's Comirnaty COVID-19 vaccines. Such ef- forts towards precision medicine, however, come with the challenge of increasing complexity (e.g., compared to small-molecule drugs). This complexity demands drug developers and manufacturers use the right ana- lytical tools to fully understand their products. Nowhere is this complexity more evident than in the lipid nanoparticles (LNPs) used to encapsulate f ragile mRNA cargo. Size, composition, aggrega- tion, surface charge, and structure of LNPs can all have significant effects on a therapeutic molecule's success; and optimizing one property may come at the detriment of another. These interdependent char- acteristics can impact stability during production, transport, and storage, or affect the delivery and re- lease of the drug product in target tissues. Challenges of LNP characterization Unlike small-molecule drugs or protein therapeutics, which are chemically or biologically synthesized, LNPs self-assemble during the mixing of their com- ponent ingredients. These components can include cationic lipids, helper lipids such as distearoylphos- phatidylcholine (DSPC), sterols such as cholesterol, and polyethylene glycol-containing (i.e., PEGylated) lipids (Figure 1). To ensure drug formulators achieve their final product, they must optimize the ratios of these ingredients and perfect the way in which these ingredients are mixed. Small batch-to-batch differences in mixing can re- sult in products that have significantly different com- positions. Similarly, changes in ingredient f low rates can alter the size of the final product. For example, faster f low rates produce smaller LNPs than slower ones. Throughout process development and optimi- zation, drug manufacturers need to confirm they are producing LNPs consistently and to specification. Shining a Light on Lipid Nanoparticle Characterization Hanna Jankevics Jones, PhD, and Natalia Markova, PhD, are pharmaceutical segment marketing managers at Malvern Panalytical. Using an orthogonal approach to lipid nanoparticle analysis can increase the odds of project success. LIK ANARIS - STOCK.ADOBE.COM