ArticlePharmaceutical research2018
Influence of Fatty Acid Modification on Uptake of Lovastatin-Loaded Reconstituted High Density Lipoprotein by Foam Cells.
Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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0 citing papers in PubMed, 4 citations in OpenAlex.
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6 authors at 1 institution in 1 country.
Funding
Abstract
purposeSpherical reconstituted high density lipoprotein (rHDL) can target atherosclerotic lesions by the very low density lipoprotein (VLDL) receptor, which is seldom expressed in liver. By promoting this pathway, the targeting efficiency was hyphothesized to be improved due to avoiding undesired uptake in liver mediated by the scavenger receptor class B type I (SR-BI). In this study, how fatty acid modification in spherical rHDL influenced the VLDL receptor-mediated endocytosis pathway was investigated.
methodsStearic acid (SA) and arachidonic acid (AA) with different saturation levels were utilized to modify the lovastatin-loaded rHDL (LS-rHDL). Phagocytosis test on foam cells with or without cholesteryl ester transfer protein (CETP) expression was conducted to observe the cellular uptake of the SA or AA modified rHDL and the non-modified one. Raman spectroscopy, guanidine hydrochloride (Gdn-HCl) denaturation experiment and in vitro evaluation of drug release were used to analyze the related mechanism.
resultsIn comparison with the non-modified rHDL, AA modification could reduce the packing order of the rHDL phospholipid acyl chains, leading to the decreased apoA-I binding extent with lipid and the increased drug release, while the opposite was true for SA modification. The AA-modified rHDL exhibited a higher uptake of foam cells expressing CETP than the non-modified one, while the SA-modified one showed the lowest cellular uptake among the three rHDLs.
conclusionsIncreased unsaturation level can facilitate lipid-interchange process where the cargo in rHDL core may transfer to VLDL more easily, and then promote the endocytosis mediated by the VLDL receptor.
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