Lipid-Polyhydroxyalkanoate Hybrid Nanoparticles as Sustainable Platform for mRNA delivery

Area of Science:

• Biotechnology
• Materials Science
• Nanomedicine

Background:

• The success of mRNA vaccines has spurred interest in mRNA therapeutics, necessitating advanced delivery systems.
• Lipid-based and polymeric nanoparticles are established delivery platforms, but hybrid systems offer enhanced properties.
• There is a need for sustainable alternatives to conventional materials like PLGA in nanoparticle formulation.

Purpose of the Study:

• To develop and characterize novel lipid-polymer hybrid nanoparticles (LPHNPs) for mRNA delivery.
• To evaluate sustainable medium-chain-length polyhydroxyalkanoates (mcl-PHAs) as a component in LPHNPs.
• To assess the physico-chemical properties, stability, and biological performance of mRNA-loaded LPHNPs.

Main Methods:

• Synthesis of LPHNPs using a scalable microfluidic process with mcl-PHAs and cationic lipids (DOTAP).
• Characterization of LPHNPs including physico-chemical properties, cell toxicity, and transfection efficiency in HeLa and hCMEC/D3 cells.
• Evaluation of lyophilization stability, storage at various temperatures, and in vivo biodistribution after intravenous injection in mice.

Main Results:

• LPHNPs were successfully synthesized with tunable properties based on polymer-to-lipid ratios and mcl-PHA composition.
• mRNA-LPHNPs demonstrated good transfection efficiency and stability in cell cultures, with no significant toxicity.
• Particles maintained their properties after lyophilization and prolonged storage, and showed broad organ distribution in vivo with limited blood interactions.

Conclusions:

• Modular LPHNPs based on sustainable mcl-PHAs offer a promising alternative to conventional mRNA delivery systems.
• The developed LPHNPs exhibit excellent stability, efficacy, and storage capabilities, suitable for therapeutic mRNA delivery.
• This approach advances the development of sustainable nanocarriers for next-generation mRNA therapeutics.