Novel cubosome system resistant to lipid removal by serum albumin

Cubosomes are lipidic nanoparticles containing bicontinuous cubic structures. Their unique architecture and potential as drug delivery vehicles have attracted researchers’ attention. However, cubosome systems that are more robust in the presence of plasma components are being sought after for applications in intravenous administration. In this study, we prepared cubosomes consisting of 1,2-dioleoyl-sn-glycero-3-hex-ylphosphocholine (hexyl-DOPC) and compared their interaction with bovine serum albumin (BSA), the most abundant protein in plasma, with that of conventional cubosome systems consisting of several bicontinuous cubic phase-forming lipids, including 1-monoolein (MO), 1-O-(5,9,13,17-tetramethyloctadecanoyl)erythritol (EROCO C22), or 1-O-(5,9,13,17-tetramethyloctadecyl)-β-D-xylopyranoside (β-XP). The average number of lipids bound to each BSA molecule was between 1.2–4.0 for MO, EROCO C22, and β-XP. On the other hand, hexyl-DOPC exhibited negligible binding to BSA. This result suggests that hexyl-DOPC, which was shown to resist removal from particles by BSA, can be used as a new lipid component of cubosomes, and has higher plasma stability than the other cubic phase-forming lipids.