Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Sep 10:8:100283.
doi: 10.1016/j.ijpx.2024.100283. eCollection 2024 Dec.

Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery

Affiliations
Review

Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery

Md Anamul Haque et al. Int J Pharm X. .

Abstract

Nucleic acid-based therapeutics are a common approach that is increasingly popular for a wide spectrum of diseases. Lipid nanoparticles (LNPs) are promising delivery carriers that provide RNA stability, with strong transfection efficiency, favorable and tailorable pharmacokinetics, limited toxicity, and established translatability. In this review article, we describe the lipid-based delivery systems, focusing on lipid nanoparticles, the need of their use, provide a comprehensive analysis of each component, and highlight the advantages and disadvantages of the existing manufacturing processes. We further summarize the ongoing and completed clinical trials utilizing LNPs, indicating important aspects/questions worth of investigation, and analyze the future perspectives of this significant and promising therapeutic approach.

Keywords: Lipid nanoparticles; Microfluidics; Transfection; mRNA; siRNA.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interest.

Figures

Unlabelled Image
Graphical abstract
Fig. 1
Fig. 1
Cellular uptake and endosomal escape of nucleic acid carrying lipid nanoparticles into the cytosol to modulate gene expression. Image was created using BioRender.com
Fig. 2
Fig. 2
Graphical illustration of lipid-based systems used for nucleic acid delivery. The image was created with BioRender.com
Fig. 3
Fig. 3
LNP formulation using microfluidic setups involves pump systems for regulating the flow of ethanolic and aqueous solutions for mixing in the microfluidic chip. (a) Representative formulation setup for LNPs; (b) Representative microfluidic chips used for mixing the two solutions and producing the LNPs. The image was created with BioRender.com

References

    1. Abrams M.T., Koser M.L., Seitzer J., Williams S.C., DiPietro M.A., Wang W., Shaw A.W., Mao X., Jadhav V., Davide J.P., Burke P.A., Sachs A.B., Stirdivant S.M., Sepp-Lorenzino L. Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle: effect of dexamethasone co-treatment. Mol. Ther. 2010;18:171–180. - PMC - PubMed
    1. Adams D., Gonzalez-Duarte A., O’Riordan W.D., Yang C.C., Ueda M., Kristen A.V., Tournev I., Schmidt H.H., Coelho T., Berk J.L., Lin K.P., Vita G., Attarian S., Planté-Bordeneuve V., Mezei M.M., Campistol J.M., Buades J., Brannagan T.H., 3rd, Kim B.J., Oh J., Parman Y., Sekijima Y., Hawkins P.N., Solomon S.D., Polydefkis M., Dyck P.J., Gandhi P.J., Goyal S., Chen J., Strahs A.L., Nochur S.V., Sweetser M.T., Garg P.P., Vaishnaw A.K., Gollob J.A., Suhr O.B. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 2018;379:11–21. - PubMed
    1. Akinc A., Maier M.A., Manoharan M., Fitzgerald K., Jayaraman M., Barros S., Ansell S., Du X., Hope M.J., Madden T.D., Mui B.L., Semple S.C., Tam Y.K., Ciufolini M., Witzigmann D., Kulkarni J.A., van der Meel R., Cullis P.R. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 2019;14:1084–1087. - PubMed
    1. Alabi C.A., Love K.T., Sahay G., Yin H., Luly K.M., Langer R., Anderson D.G. Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery. Proc. Natl. Acad. Sci. USA. 2013;110:12881–12886. - PMC - PubMed
    1. Albakr L., Alqahtani F.Y., Aleanizy F.S., Alomrani A., Badran M., Alhindas H., Al-Mohanna F. Improved delivery of miR-1296 loaded cationic nanoliposomes for effective suppression of triple negative breast cancer. Saudi Pharmaceut. J. 2021;29:446–455. - PMC - PubMed

LinkOut - more resources