Ruppel, Paula Marie (2023) DEVELOPMENT OF A ROBUST PRODUCTION METHOD OF LIPID NANOPARTICLES FOR mRNA DELIVERY. Master's Research Project 2, Medical Pharmaceutical Sciences.
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Abstract
After the approval of ONPATTRO and the mRNA-based SARS-COVID-19 vaccines the field of nanomedicine jumped forward and revolutionized the treatment of genetic diseases and vaccination. In this thesis, the formulation of ONPATTRO will be employed to develop a robust microfluidic production process for mRNA-carrying lipid nanoparticles (LNPs) that can be utilized for pulmonary vaccination in the future. Therefore, quality criteria for the particle size, the polydispersity index, the zeta potential, and the encapsulation efficiency were introduced as the goal of the production method. With the aim of process optimization different variables were altered and adjusted. Two different microfluidic pumps were tested for their ability to produce LNPs of the expected quality. Furthermore, flow rates and mixing dynamics were changed to improve the production, and the partial or complete replacement of cholesterol with β-sitosterol was analyzed. The LNPs with the best quality were ultimately successfully tested in HeLa cells for quantitative and in a lung cell line for qualitative uptake. These results build a solid fundament for the successful production of LNPs for future applications.
| Item Type: | Thesis (Master's Research Project 2) |
|---|---|
| Supervisor name: | Frijlink, H.W. and Hinrichs, W.L.J. and Jansen, E.M. |
| Degree programme: | Medical Pharmaceutical Sciences |
| Thesis type: | Master's Research Project 2 |
| Language: | English |
| Date Deposited: | 27 Nov 2023 09:16 |
| Last Modified: | 27 Nov 2023 09:16 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/31679 |
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