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Kumari Kajal, Shrestha Ishita, Singh Hare Ram, Sampath Muthu Kumar
Keywords: Solid lipid nanoparticles, Drug delivery systems, mRNA delivery, Preparation-characterization techniques
Lipid nanoparticles have emerged as versatile and biocompatible nanocarriers, capable of improving the solubility, stability, and bioavailability of hydrophilic and hydrophobic therapeutic agents. This review summarizes major preparation techniques, which comprise high-pressure homogenization, solvent emulsification-evaporation, solvent injection, microemulsion templating, phase inversion temperature processing, and supercritical fluid-based methods, with the emphasis on their operational principles, advantages, and limitations. The most relevant characterization strategies, like particle sizing, surface charge analysis, crystallinity assessment, and microscopic imaging, are introduced with the aim of emphasizing their importance to determine critical physicochemical quality and performance attributes of LNPs. The review further examines the current applications of LNPs in drug delivery, including gene therapy, mRNA vaccines, monoclonal antibody expression, and regenerative medicine, pointing out their ability to protect labile molecules, enhance targeting, and provide for controlled release. Besides established capabilities, this manuscript discusses the major challenges that constrain broader clinical translation: namely, formulation instability, limited loading of certain drugs, processing variability during scale-up, and inconsistent in vivo behaviour driven by protein corona formation and rapid clearance. Future advances are foreseen with rational lipid design, hybrid lipid–polymer systems, continuous-flow manufacturing, and computational formulation tools, which together hold promise to address these bottlenecks and extend the therapeutic potential of LNPs. Overall, this review provides a consolidated perspective on current methodologies, functional attributes, emerging challenges, and forward-looking strategies that will shape the next generation of lipid nanoparticle-based drug delivery systems.
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Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, India