TY - JOUR
T1 - Lipid Nanoparticle Technologies after the mRNA Platform Era: Manufacturing Fragility, Platform Logic, and System Design
AU - Sven Larsson
AU - Erik Johansson
AU - Anna Nilsson
JF - EAMD 3
Y1 - 0
VL - 0
IS - 0
SP - 187
N2 - The clinical success of mRNA–lipid nanoparticle vaccines transformed lipid nanoparticle technology from a specialised drug delivery field into a central modality for modern biopharmaceutical development. That success demonstrated that nucleic acid therapeutics can be manufactured, distributed, and deployed at unprecedented speed when formulation science, process engineering, and regulatory urgency align. Yet the same success also exposed how dependent LNP products remain on tightly constrained composition, process history, and cold-chain stability. The central problem is that processes optimised rapidly under pandemic conditions do not automatically constitute robust manufacturing platforms. Many LNP processes remain product-specific, empirically tuned, and sensitive to changes in lipid composition, aqueous phase conditions, mixing geometry, and downstream handling. The language of “platform” is therefore often stronger than the underlying evidence for generalisable process robustness. The review maps the structural and functional logic of LNP platforms, evaluates how mRNA delivery requirements shaped formulation choices, and assesses preclinical and manufacturing evidence across laboratory, preclinical, and scalable production contexts. It identifies recurrent fragility points including mixing sensitivity, particle heterogeneity, aggregation, mRNA degradation, storage instability, and incomplete comparability evidence after process change. Five tables summarise platform design, mRNA delivery requirements, manufacturing evidence, fragility points, and a system design strategy for robust LNP production. The post-mRNA era requires a shift from emergency product development to platform-centred system design. LNP manufacturing must become modular, measurable, scalable, and quality-resilient rather than merely reproducible under narrowly defined conditions. Achieving this transition is essential if LNP technologies are to move beyond COVID-19 vaccines into broader therapeutic applications and more equitable global health deployment.
UR - https://pubsys.eshragh.co/n105134582
ER -