Title

Lipidoid nanoparticles increase ATP uptake into hypoxic brain endothelial cells

DOI

10.1016/j.ejpb.2022.10.011

Document Type

Journal Article

Publication Date

11-1-2022

Publication Title

European Journal of Pharmaceutics and Biopharmaceutics

Volume

180

First Page

238

Last Page

250

ISSN

9396411

Keywords

ATP delivery, Brain endothelial cells, C12-200, Lipidoid nanoparticle, PEG-DMG

Abstract

Lipidoid nanoparticles (LNPs) are clinically successful carriers for nucleic acid delivery to liver and muscle targets. The ability of LNPs to load and deliver small molecule drugs has not been reported yet. We propose that the delivery of adenosine triphosphate (ATP) to brain endothelial cells (BECs) lining the blood–brain barrier may increase cellular energetics of the injured BECs. We formulated and studied the physicochemical characteristics of ATP-loaded LNPs using the C12-200 ionizable cationic lipid and other helper lipids. Polyethylene glycol-dimyristoyl glycerol (PEG-DMG), one of the helper lipids, played a crucial role in maintaining colloidal stability of LNPs over time whereas the inclusion of both ATP and PEG-DMG maintained the colloidal stability of LNPs in the presence of serum proteins. ATP-LNPs formulated with PEG-DMG resulted in a 7.7- and 6.6- fold increased uptake of ATP into normoxic and hypoxic BECs, respectively. Altogether, our results demonstrate the potential of LNPs as a novel carrier for the delivery of small molecular mass actives to BECs—a CNS target.

Open Access

Green Accepted

Share

COinS