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Nanolipoprotein Particles as a Delivery Platform for Fab Based Therapeutics
Martine Darwish1, Whitney Shatz1, Brandon Leonard1
1Genentech, South San Francisco, California 94088, United States.
Bioconjugate Chemistry
|July 24, 2020
Summary
Nanolipoprotein particles (NLPs) enable high-density multivalent delivery of antibody fragments (Fabs). This novel Fab-NLP platform demonstrates enhanced stability and manufacturability for therapeutic applications.
Area of Science:
- Biotechnology
- Nanomedicine
- Drug Delivery Systems
Background:
- Nanolipoprotein particles (NLPs) are a lipid bilayer nanoparticle platform for in vivo molecule delivery.
- The potential of NLPs for delivering high-valency antibody fragments (Fabs) has not been explored.
Purpose of the Study:
- To develop, optimize, and characterize nanolipoprotein particle-Fab (Fab-NLP) conjugates.
- To evaluate the manufacturability and stability of Fab-NLPs for therapeutic delivery.
Main Methods:
- NLPs were assembled with maleimide-reactive lipids at pH 6 for site-specific Fab conjugation.
- Conjugation efficiency, particle characteristics (molecular weight, hydrodynamic radius), viscosity, and lyophilization stability were assessed.
- Fab activity and serum stability of Fab-NLPs were evaluated.
Main Results:
- Up to 30 Fabs were conjugated per NLP with minimal impact on hydrodynamic radius.
- Fab-NLPs achieved higher concentrations than Fab-PEG conjugates and maintained Fab activity.
- Fab-NLPs exhibited increased stability in 50% serum (>63% intact after 24h at high ratios).
Conclusions:
- Fab-NLPs represent a promising platform for multivalent Fab delivery.
- The platform is compatible with manufacturing processes and shows enhanced stability and activity.
- This technology holds potential for targeted delivery of Fabs in various therapeutic settings.
