Toward a large-batch manufacturing process for silicon-stabilized lipid nanoparticles: A highly customizable RNA...

Area of Science:

• Biotechnology
• Nanomedicine
• Drug Delivery

Background:

• Lipid nanoparticles (LNPs) are crucial for RNA therapeutics but face challenges in RNA stability and shelf life.
• Silicon-stabilized hybrid lipid nanoparticles (sshLNPs) offer enhanced stability and post-hoc RNA loading capabilities.
• Previous sshLNP production methods were not suitable for large-scale manufacturing.

Purpose of the Study:

• To develop a scalable manufacturing process for silicon-stabilized hybrid lipid nanoparticles (sshLNPs).
• To enable multikilogram batch production of sshLNPs for clinical translation.
• To ensure the physical and functional equivalence of large-scale produced sshLNPs compared to small-scale methods.

Main Methods:

• Developed a revised protocol using solvent injection mixing for nanoparticle formation.
• Incorporated in-flow extrusion for multiliter volumes.
• Optimized tangential flow filtration for residual organic solvent removal.

Main Results:

• Successfully established a manufacturing process enabling 2 kg finished batches of sshLNPs.
• Demonstrated that large-scale produced sshLNPs possess equivalent physical and functional properties to small-scale batches.
• The new workflow supports Good Manufacturing Practice (GMP) protocols.

Conclusions:

• A scalable, solvent-injection-based manufacturing process for sshLNPs has been successfully developed.
• This advancement facilitates the clinical translation and large-scale deployment of sshLNP technology for RNA therapeutics.
• The optimized process ensures the quality and efficacy of sshLNPs for future therapeutic applications.