Factors Affecting Enhanced Permeation of Amphotericin B Across Cell Membranes and Safety of Formulation

Autor: Tan Suwandecha, Kajiram Adhikari, Ekawat Thawithong, Teerapol Srichana, Wilaiporn Buatong
Rok vydání: 2015
Předmět:
Lipopolysaccharide
Chemistry
Pharmaceutical
Lipid Bilayers
Phospholipid
Pharmaceutical Science
Nanotechnology
02 engineering and technology
Aquatic Science
030226 pharmacology & pharmacy
Permeability
Cell Line
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Griess test
Amphotericin B
Ergosterol
parasitic diseases
Drug Discovery
Humans
Lipid bilayer
Ecology
Evolution
Behavior and Systematics
Phospholipids
Chromatography
Ecology
urogenital system
Chemistry
Cell Membrane
technology
industry
and agriculture
General Medicine
Permeation
bacterial infections and mycoses
021001 nanoscience & nanotechnology
Lipids
Drug Combinations
Membrane
Cholesterol
HEK293 Cells
Alveolar macrophage
lipids (amino acids
peptides
and proteins)
0210 nano-technology
Agronomy and Crop Science
Deoxycholic Acid
Zdroj: AAPS PharmSciTech. 17(4)
ISSN: 1530-9932
Popis: The aim of this study was to determine amphotericin B (AmB) permeation across lipid bilayer membranes mounted on Transwell® and to observe the phagocytosis of the AmB and the AmB-lipid formulations by alveolar macrophage (AM) cell lines using a fluorescence microscope. The lipid bilayer membranes were prepared from phospholipid and ergosterol as well as phospholipid and cholesterol in a ratio (67:33 mol%). AmB-lipid formulations were prepared from AmB incorporated with four lipid derivatives during a lyophilization process. In vitro cytotoxicity studies were carried out on kidney cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of nitric oxide production by AMs exposed to these AmB-lipid formulations were determined by the Griess reaction. Phagocytosis of the AmB-lipid formulations was carried out using AM cells. The lipid bilayer membranes and AmB-lipid formulations were successfully prepared. In vitro cytotoxicity results showed less toxicity to kidney cells than pure AmB, and a 1,000-fold less production of nitric oxide by NR8383 cell lines was obtained when compared to lipopolysaccharide. Permeation results were two- to fivefold higher than for pure AmB in the ergosterol containing lipid bilayer and two- to fourfold higher than AmB in the cholesterol containing compositions, both of which were enough to kill the fungi according to their MICs and MFCs. AM phagocytosed the AmB-lipid formulations. We suggest that these products especially the AmB-sodium deoxycholate sulfate are potential candidates for targeting AM cells for the treatment of invasive pulmonary aspergillosis.
Databáze: OpenAIRE
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