Lyophilization of nucleic acid nanoparticles

Kasper, Julia Christina (2012): Lyophilization of nucleic acid nanoparticles: Formulation Development, Stabilization Mechanisms, and Process Monitoring. Dissertation, LMU München: Faculty of Chemistry and Pharmacy

Abstract

The objective of the thesis was the lyophilization of cationic polymer-based pDNA or siRNA nanoparticles (i.e. polyplexes) with a special focus on the development of long-term stable formulations, the investigation of stabilization mechanisms especially during freezing, and the advanced monitoring of the lyophilization process. It was shown that an up-scaled preparation method in combination with subsequent lyophilization is a promising approach to reproducibly achieve long-term stable pDNA or siRNA polyplexes maintaining particle size and biological activity at pharmaceutically defined high quality. The results demonstrated that formulation development, highly dependent on the used type of polymer or nucleic acid, and process development, with a strong focus on the freezing, in combination with appropriate process monitoring needs always to be performed hand in hand. All in all, this thesis makes an essential contribution in order to move closer from a promising biotechnological approach towards clinic-friendly drugs.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Lyophilization, Freeze-Drying, Freezing, Nanoparticles, Polyplexes, siRNA, pDNA, Formulation, Process Monitoring
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 540 Chemistry and allied sciences
• Faculties: Faculty of Chemistry and Pharmacy
• Language: English
• Date of oral examination: 17. April 2012
• 1. Referee: Frieß, Wolfgang
• Signature of the printed copy: 0001/UMC 20653