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Design of Experiments Grants Mechanistic Insights into the Synthesis of Spermine-Containing PBAE Copolymers.
- Source :
-
ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2024 Jul 24; Vol. 16 (29), pp. 37545-37554. Date of Electronic Publication: 2024 Jul 10. - Publication Year :
- 2024
-
Abstract
- Successful therapeutic delivery of siRNA with polymeric nanoparticles seems to be a promising but not vastly understood and complicated goal to achieve. Despite years of research, no polymer-based delivery system has been approved for clinical use. Polymers, as a delivery system, exhibit considerable complexity and variability, making their consistent production a challenging endeavor. However, a better understanding of the polymerization process of polymer excipients may improve the reproducibility and material quality for more efficient use in drug products. Here, we present a combination of Design of Experiment and Python-scripted data science to establish a prediction model, from which important parameters can be extracted that influence the synthesis results of polybeta-amino esters (PBAEs), a common type of polymer used preclinically for nucleic acid delivery. We synthesized a library of 27 polymers, each one at different temperatures with different reaction times and educt ratios using an orthogonal central composite (CCO-) design. This design allowed a detailed characterization of factor importance and interactions using a very limited number of experiments. We characterized the polymers by analyzing the resulting composition by 1H-NMR and the size distribution by GPC measurements. To further understand the complex mechanism of block polymerization in a one-pot synthesis, we developed a Python script that helps us to understand possible step-growth steps. We successfully developed and validated a predictive response surface and gathered a deeper understanding of the synthesis of polyspermine-based amphiphilic PBAEs.
Details
- Language :
- English
- ISSN :
- 1944-8252
- Volume :
- 16
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- ACS applied materials & interfaces
- Publication Type :
- Academic Journal
- Accession number :
- 38985802
- Full Text :
- https://doi.org/10.1021/acsami.4c06079