Transport and transfer of bioactive substances with high density lipoprotein particles

Publikation: KonferenzbeitragPoster

Abstract

Transport and transfer of bioactive substances with high-density lipoprotein particles

Lipoprotein particles are micellar, natural transport vehicles in higher organisms, consisting of distinct proteins and non-covalently bound lipids in the range of a few nanometers up to a hundred nanometers. Besides, lipoproteins can be used as an effective shuttle for food supplements (vitamins), since the core is very well suited for the absorption of many hydrophobic antineoplastic (water-insoluble) active substances and can keep them encapsulated until they are released. In addition, hydrophilic agents can be incorporated into HDL shell after chemical binding to lipids for drug delivery. Due to its controlled dynamic metabolism, its stability in blood plasma and cell type-specific interaction, lipoprotein mimetic offers excellent opportunities to design a promising drug shuttle. The aim of this work is to use HDL particles as drug carriers and suppliers in therapeutic applications. Specifically, HIS6-labelled lipophobic drugs were anchored to the envelope of the HDL particles via 18:1 DGS Ni-NTA lipid head groups. To characterize the loading efficiency, the co-localization of fluorescence-labelled HDL proteins and DGS Ni-NTA lipids (ATTO 488) was analyzed using Single Molecule Florescence Microscopy (SMFM). Moreover, the interaction and transfer efficiency of drug carrying HDL shuttles was investigated by diffusional analysis of dual labeled HDL particles on supported lipid membranes. As a demonstration of the biologically active effect of the anchored drugs in the HDL shuttles, supplied HIS6-labelled insulin was used to stimulate the translocation of transiently transfected GLUT4-eGFP1 within CHOK1 cells. The mean membrane intensity of stimulated cells was determined in giant plasma membrane vesicles via FM.
Based on our previously published data2 we can assume that HDL particles fuse with artificial membranes. Indeed, by adding preloaded HDL particles to a planar lipid membrane, we observed transfer and diffusion of anchored active substances. Diffusion analysis yielded a successful in-cooperation of HIS6-tagged lipophobic drugs anchored via Ni-NTA-lipids within membranes. The cell-based tests have demonstrated that the HDL-anchored insulin retains its biological activity. Recently, we demonstrated that hydrophobic dietary supplements can be incorporated into the HDL core by reconstitution of HDL particles. These two approaches show an effective use of HDL particles as a drug delivery system.

1. Lanzerstorfer P, Stadlbauer V, Chtcheglova LA, et al. Identification of novel insulin mimetic drugs by quantitative total internal reflection fluorescence (TIRF) microscopy. Br J Pharmacol. 2014;171(23):5237-5251. doi:10.1111/bph.12845
2. Plochberger B, Röhrl C, Preiner J, et al. HDL particles incorporate into lipid bilayers-a combined AFM and single molecule fluorescence microscopy study. Sci Rep. 2017;7(1). doi:10.1038/s41598-017-15949-7

OriginalspracheDeutsch (Österreich)
Seiten-
Seitenumfang1
PublikationsstatusVeröffentlicht - 2020
VeranstaltungLinz Winter Workshop 2020 - Linz, Österreich
Dauer: 31 Jän 20203 Feb 2020

Konferenz

KonferenzLinz Winter Workshop 2020
Land/GebietÖsterreich
OrtLinz
Zeitraum31.01.202003.02.2020

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