Quantification of Surface GalNAc Ligands Decorating Nanostructured Lipid Carriers by UPLC-ELSD.

Autor: Gauthier L; Université Grenoble Alpes, CEA, LETI-DTBS, F-38000 Grenoble, France.; Université Grenoble Alpes, CEA, CNRS, IRIG-SyMMES, F-38000 Grenoble, France., Varache M; Université Grenoble Alpes, CEA, LETI-DTBS, F-38000 Grenoble, France., Couffin AC; Université Grenoble Alpes, CEA, LETI-DTBS, F-38000 Grenoble, France., Lebrun C; Université Grenoble Alpes, CEA, CNRS, IRIG-SyMMES, F-38000 Grenoble, France., Delangle P; Université Grenoble Alpes, CEA, CNRS, IRIG-SyMMES, F-38000 Grenoble, France., Gateau C; Université Grenoble Alpes, CEA, CNRS, IRIG-SyMMES, F-38000 Grenoble, France., Texier I; Université Grenoble Alpes, CEA, LETI-DTBS, F-38000 Grenoble, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2019 Nov 12; Vol. 20 (22). Date of Electronic Publication: 2019 Nov 12.
DOI: 10.3390/ijms20225669
Abstrakt: Nanoparticles have been extensively studied for drug delivery and targeting to specific organs. The functionalization of the nanoparticle surface by site-specific ligands (antibodies, peptides, saccharides) can ensure efficient recognition and binding with relevant biological targets. One of the main challenges in the development of these decorated nanocarriers is the accurate quantification of the amount of ligands on the nanoparticle surface. In this study, nanostructured lipid carriers (NLC) were functionalized with N-acetyl-D-galactosamine (GalNAc) units, known to target the asialoglycoprotein receptor (ASGPR). Different molar percentages of GalNAc-functionalized surfactant (0%, 2%, 5%, and 14%) were used in the formulation. Based on ultra-high-performance liquid chromatography separation and evaporative light-scattering detection (UPLC-ELSD), an analytical method was developed to specifically quantify the amount of GalNAc units present at the NLC surface. This method allowed the accurate quantification of GalNAc surfactant and therefore gave some insights into the structural parameters of these multivalent ligand systems. Our data show that the GalNAc decorated NLC possess large numbers of ligands at their surface and suitable distances between them for efficient multivalent interaction with the ASGPR, and therefore promising liver-targeting efficiency.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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