Serum albumin-lipid membrane interaction influencing the uptake of porphyrins

Rita Galántai, Irén Bárdos-Nagy, Károly Módos, József Kardos, Péter Závodszky, Judit Fidy

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23 Citations (Scopus)

Abstract

It is frequently observed in pharmaceutical practice that entrapped substances are lost rapidly when liposomes are used as carriers to introduce substances into cells. The reason for the loss is the interaction of serum components with liposomes. To elucidate the mechanism of this phenomenon the partition of mesoporphyrin (MP) was systematically studied in model systems composed of various lipids and human serum albumin (HSA). As surface charge is an important factor in the interaction, neutral (1,2-dimyristoyl-sn- glycero-3-phosphatidylcoline, DMPC) and negatively charged (1,2-dimyristoyl- sn-glycero-3-phosphatidylcoline/1,2-dimyristoyl-sn-glycero-3- phosphatidylglycerol, DMPC/DMPG = 19/1 w/w) lipids were compared. The liposome/apomyoglobin system was the negative control. The size distribution of sonicated samples was carefully analyzed by dynamic light scattering. Constants of association of MP to the proteins and to the liposomes were determined: K(p,1) = (2.5 ± 0.7) x 107 M-1, K(p,2) = (1.0 ± 0.7) x 108 M-1, K(L,1) = (1.3 ± 0.3) x 105 M-1, and K(L,2) = (3.2 ± 0.6) X 104 M-1 for HSA, apomyoglobin, DMPC, and DMPC/DMPG liposomes, respectively. These data were used to evaluate the partition experiments. The transfer of MP from the liposomes to the proteins was followed by fluorescence spectroscopy. In the case of apomyoglobin, the experimental points could be interpreted by ruling out the protein-liposome interaction. In the case of HSA, the efflux of MP from the liposomes was strongly inhibited above a critical HSA concentration range for negatively charged vesicles. This effect was interpreted as the result of HSA coat formation on the liposome surface. This direct interaction is significant for small liposomes. The interpretation is fully supported by differential scanning calorimetry experiments.

Original languageEnglish
Pages (from-to)261-270
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume373
Issue number1
DOIs
Publication statusPublished - Jan 1 2000

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Keywords

  • Differential scanning calorimetry
  • Fluorescence
  • Human serum albumin
  • Liposome
  • Mesoporphyrin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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