An assessment of pH-sensitive cationic lipid nanoparticles for drug delivery
A recent review in the Chemical and Pharmaceutical Bulletin looks at the molecular design of pH-sensitive cationic lipids and their applications for various tissues and cell types. The researchers also describe the application of lipid nanoparticles (LNPs) for delivering various macromolecules including small interfering ribonucleic acid (siRNA), antisense oligonucleotide, messenger RNA (mRNA), and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system. A variety of diseases caused by mutations and misregulation of gene expressions are difficult to treat using conventional drugs due to limitations in their selectivity, affinity, and the role of untranslated RNAs. Therefore, several alternative approaches have been adopted to treat various refractory diseases. For example, Onpattro® is a first-ever RNA interference (RNAi) medicine that is used in the treatment of familial amyloid polyneuropathy caused by mutations in the transthyretin gene.
These siRNA medicines and mRNA vaccines are lipid nanoparticle (LNP) preparations. LNP encapsulates the drug or protein of interest, thereby protecting it from enzymatic degradation and efficiently delivering it into the cytosol of the target cells. Typically, LNPs are composed of 4 types of lipids including a cationic lipid (CL), a phospholipid (PL), cholesterol, and a pegylated (PEG)-lipid. Currently, pH-sensitive CLs are the gold standard. More specifically, the tertiary amine-based pH-sensitive CLs are near neutral at physiological pH and develop cationic properties in a weakly acidic environment. With research into the best endosomal escape, stability maximized fusogenic activity, cytosolic delivery, and efficient activity, the development of potent CLs is one of the breakthroughs in the field of LNPs. The current study also addresses the important aspects of how to improve the biosafety of the LNPs including maximizing hepatocyte-specificity, reducing the CL dose, and developing of biodegradable CLs.
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