Lipid Nanoparticles for Drug Delivery

TLDR

Lipid nanoparticles have garnered significant interest over the past two decades, achieving clinical success since Doxil in 1995 and demonstrating strong potential for delivering nucleic acid drugs, including RNA therapies and mRNA COVID‑19 vaccines. This review aims to provide an overview of lipid nanoparticle classes—liposomes, solid lipid nanoparticles, and nanostructured lipid carriers—and to introduce their preparation methods. The authors review lipid nanoparticle characterization techniques and highlight their use for encapsulating hydrophobic, hydrophilic, and RNA drugs, as well as strategies to overcome delivery barriers such as the blood–brain barrier, targeted delivery, and diverse administration routes. Lipid nanoparticles offer biocompatibility, ease of preparation, scalable production, non‑toxicity, and targeted delivery, yet further research is needed on structure–function relationships, large‑scale manufacturing, and precise targeting to fully realize their clinical potential.

Abstract

Lipid nanoparticles have attracted significant interests in the last two decades, and have achieved tremendous clinical success since the first clinical approval of Doxil in 1995. At the same time, lipid nanoparticles have also demonstrated enormous potential in delivering nucleic acid drugs as evidenced by the approval of two RNA therapies and mRNA COVID‐19 vaccines. In this review, an overview on different classes of lipid nanoparticles, including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, is first provided, followed by the introduction of their preparation methods. Then the characterizations of lipid nanoparticles are briefly reviewed and their applications in encapsulating and delivering hydrophobic drugs, hydrophilic drugs, and RNAs are highlighted. Finally, various applications of lipid nanoparticles for overcoming different delivery challenges, including crossing the blood–brain barrier, targeted delivery, and various routes of administration, are summarized. Lipid nanoparticles as drug delivery systems offer many attractive benefits such as great biocompatibility, ease of preparation, feasibility of scale‐up, nontoxicity, and targeted delivery, while current challenges in drug delivery warrant future studies about structure–function correlations, large‐scale production, and targeted delivery to realize the full potential of lipid nanoparticles for wider clinical and pharmaceutical applications in future.