Innovative approaches in polymer nanoparticle synthesis for RNA therapeutics

RNA therapy with polymer nanoparticles is considered a promising approach for the treatment of various illnesses. It involves the use of polymers as "nanocarriers" to transport RNA drugs precisely to the correct target cells. Manufacturing such polymers, however, has proven to be complex and difficult.

In a recent study by the research group of Olivia Merkel, Professor of Drug Delivery in the Department of Pharmacy at LMU, so-called spermine-modified poly(beta-amino esters) (PBAEs), a polymer type that is frequently used for the formulation and delivery of nucleic acids were focused on. "We synthesized and characterized a library of 27 different polymers, taking into account various factors such as the ratios of starting materials, the temperature, and the reaction time," explains Merkel.

A design-of-experiment approach, whereby the significant factors of experiments are identified by means of statistical analyses, enabled the researchers to derive a wealth of information out of just a few experiments. The polymers were chemically analyzed to understand their composition and molecular properties. In addition, a computer-based protocol was developed to better capture the complex process of polymerization and predict it for future syntheses. "Our research helps to improve the quality, efficiency, and precision of RNA drugs," says Merkel regarding the results of the study.

 

Source:
Journal reference:

Kromer, A. P. E., et al. (2024). Design of Experiments Grants Mechanistic Insights into the Synthesis of Spermine-Containing PBAE Copolymers. ACS Applied Materials & Interfaces. doi.org/10.1021/acsami.4c06079.

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