Diffusion of univalent ions across the lamellae of swollen phospholipids

Bangham, A. D.; Standish, M. M.; Watkins, Johnathan

doi:10.1016/s0022-2836(65)80093-6

Cited by 4,078 publications

(1,789 citation statements)

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“…Liposomes are vesicles consisting of an aqueous core surrounded by a phospholipid bilayer [1]. They have the ability to incorporate both amphiphilic and lipophilic compounds in their membrane-like bilayer as well as to encapsulate hydrophilic compounds [2].…”

Section: Introductionmentioning

confidence: 99%

Asymmetric flow field‐flow fractionation of liposomes: optimization of fractionation variables

Hupfeld

Ausbacher

Brandl

2009

J of Separation Science

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Original Paper Asymmetric flow field-flow fractionation of liposomes: optimization of fractionation variablesThe purpose of this study was to investigate the influence of ionic strength of the carrier liquid, cross flow rate, focus flow rate, and sample load on the retention behavior of liposomes in asymmetric flow field-flow fractionation (AF4). Two differently prepared samples of large unilamellar vesicles (LUV) were used. Experiments were performed varying the factors systematically and evaluating their effect on both retention behavior of the liposomes and on particle size as obtained from online coupled multi-angle light scattering (MALS) analysis. The results showed that the focus flow rate had the least influence on the elution of liposomes. Elution of LUV is mainly governed by the chosen cross flow condition and ionic strength of the carrier liquid as well as its sample load. Optimal fractionation and size analysis were achieved using a sample load of about 10 lg, a cross flow gradient from 1.0 to 0.1 mL/min over 35 min and a carrier solution of NaNO 3 with a concentration of 10 mM. IntroductionLiposomes are vesicles consisting of an aqueous core surrounded by a phospholipid bilayer [1]. They have the ability to incorporate both amphiphilic and lipophilic compounds in their membrane-like bilayer as well as to encapsulate hydrophilic compounds [2]. Due to this ability liposomes have contributed to improving drug delivery of e.g., anthracyclines and play an important role in drug delivery research. It is widely accepted that liposomes as drug carriers may improve drug delivery in terms of therapeutic activity and safety [3 -5]. The size distribution of liposomes is important in terms of both the systemic circulation time upon injection into the blood stream and targeting abilities [3,6,7]. A study of the biodistribution of liposomes showed that the average size of the samples does not supply enough information and rather the size distribution should be used, especially for less homogeneous samples [7]. Asymmetric flow FFF (AF4) in combination with multi-angle light scattering (MALS) is the mostly applied sub-class of the FFF family and has gained increasing importance in the field of protein and peptide therapeutics as well as natural and synthetic polymers in recent years [8,9]. However, the number of publications about FFF of liposomes is rather limited compared to other applications and the technique has still not found widespread use despite it has various promising advantages over current particle size analysis methods such as photon correlation spectroscopy (PCS), and size exclusion chromatography [10,11]. For liposomal drug carriers a reliable size determination over the whole particle size spectrum from a few nanometers up to a micrometer could not be achieved with a single method so far. Such information on the other hand is essential for stringent control of the particle size which is governing the biodistribution and tumor targeting [7]. Despite a handful of successful attempts to characterize ...

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Section: Introductionmentioning

confidence: 99%

Asymmetric flow field‐flow fractionation of liposomes: optimization of fractionation variables

Hupfeld

Ausbacher

Brandl

2009

J of Separation Science

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“…Following their original description more than 30 years ago (Bangham et al, 1965), the prospect of their application to the arena of targeted drug delivery was rapidly appreciated (Gregoriadis et al, 1974). However, such conventional liposomes failed to fulfil their early promise, largely as a result of rapid clearance by the reticulo-endothelial system (RES), unpredictable patterns of extravasation and lack of longterm physicochemical stability (Gabizon, 1994).…”

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Influence of tumour size on uptake of111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model

et al. 2000

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SummaryThe relationship between tumour size and uptake of 111 In-DTPA-labelled pegylated liposomes has been examined in a human head and neck cancer xenograft model in nude mice. The mean tumour uptake of 111 In-labelled pegylated liposomes at 24 hours was 7.2 ± 6.6% ID/g. Liposome uptake for tumours < 0.1 g, 0.1-1.0 g and > 1.0 g was 15.1 ± 10.8, 5.9 ± 2.2 and 3.0 ± 1.3% ID/g, respectively. An inverse correlation between tumour weight and liposome uptake was observed by both Spearman's rank correlation test (r s = -0.573, P < 0.001) and Pearson's correlation coefficient (r s = -0.555, P < 0.001). For 18 tumours with macroscopic central necrosis, the ratio of uptake in the tumour rim relative to the necrotic tumour core was 11.2 ± 6.4. Measurement of tumour vascular volume for tumours of various sizes revealed an inverse correlation between tumour weight and tumour vascular volume (Spearman's rank correlation test, r s = -0.598, P < 0.001), consistent with poor or heterogeneous vascularization of larger tumours. These data have important implications for the clinical application of pegylated liposome targeted strategies for solid cancers which are discussed in detail.

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“…After dialysis against T N buffer immediately before use, the exchange protein was concentrated to a final concentration of 200 pg/mL against Ficoll. Hand-shaken multilamellar vesicles were freshly prepared from egg PC, 10% egg PA, and a trace of [ 14C]cholesteryl oleate, essentially as described by Bangham et al (1965) in T N buffer. After 1 h at room temperature they were centrifuged at 20000g for 30 min.…”

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confidence: 99%

Phospholipid asymmetry in Semliki Forest virus grown on baby hamster kidney (BHK-21) cells

Meer¹,

Simons²,

Kamp³

et al. 1981

Biochemistry

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ABSTRACT:The distribution of the different phospholipid classes over the two leaflets of the membrane of Semliki Forest virus, grown on baby hamster kidney cells (BHK-21), was studied. To localize the phospholipids we have used a phosphatidylcholine-specific exchange protein, a nonspecific exchange protein, phospholipases A2 and C, sphingomyelinase, and the amino group labeling reagent trinitrobenzenesulfonate. When low concentrations of exchange proteins and phospholipases were used, only those phospholipids present in lysed or otherwise defective virions were detected. Up to 10% of the phospholipids are present in such particles, and this amount correlated well with the amount of ribonuclease-degradable RNA present in each virus preparation. In the actual localization experiments, carried out with higher concentrations of exchange proteins and phospholipases as well as with trinitrobenzenesulfonate, the various independent techniques An asymmetric distribution of the different phospholipid classes over the two membrane monolayers has been observed in a variety of biological membranes. The concept of lipid asymmetry has been best documented for plasma membranes from cells which do not contain additional intracellular membrane systems such as erythrocytes, bacteria, and viruses [for a review, see Op den Kamp (1979)l. Phospholipid localization studies on plasma membranes from nucleated eukaryotic cells are much more complicated and have been carried out mainly with derivatives of the plasma membrane. In general, two approaches have been followed to obtain plasma membrane derived structures.Through the uptake of latex beads by mouse LM' cells, phagolysosomes are formed, which were considered to represent inside-out plasma membrane derivatives (Sandra & Payielded identical results. The outer membrane layer of the virus contains 52% of the phosphatidylcholine, 22% of the phosphatidylethanolamine, and 33% of the sphingomyelin. Phosphatidylserine could not be localized. Altogether 30% of the total phospholipids could be assigned to the outer layer and 50% to the inner membrane leaflet whereas 20% could not be localized. Calculations, based on the size of the Semliki Forest virus and the number of phospholipid molecules per virion, indicate it to be unlikely that the phospholipids which could not be localized are present in the inner bilayer leaflet. The present data on phospholipid composition and distribution have been compared with previous results on the lipid distribution in plasma membrane derived structures. It is concluded that an asymmetric distribution of phospholipids in the plasma membrane of various mammalian cells is apparent.

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Diffusion of univalent ions across the lamellae of swollen phospholipids

Cited by 4,078 publications

References 20 publications

Asymmetric flow field‐flow fractionation of liposomes: optimization of fractionation variables

Asymmetric flow field‐flow fractionation of liposomes: optimization of fractionation variables

Influence of tumour size on uptake of111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model

Phospholipid asymmetry in Semliki Forest virus grown on baby hamster kidney (BHK-21) cells

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