: This review describes the use of Lipid-based Nanocarriers (LNCs) for the parenteral delivery of pharmaceutical actives. Firstly, the two generation of LNCs such as ''solid lipid nanoparticles'' (SLNs) and ''nanostructured lipid carriers'' (NLCs) are explained in term of preparation, characterization and stability. Although the use of LNCs through parenteral administration has shown many benefits, their use is limited by opsonization, an immune process that causes their short half-life (3-5 min). Therefore, many strategies are discussed to realize "stealth" systems suitable for parenteral administration. Successfully, the requirements and applications of parenteral lipid nanoparticles are reviewed for the delivery of natural compounds, synthetic drugs and genetic materials. In the last period, the latter application has been a remarkable interest due to the numerous benefits of mRNA vaccines to fight the Covid-19 pandemic.
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