Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model

Orthmann, Andrea; Zeisig, Reiner; Koklic, Tilen; Šentjurc, Marjeta; Wiesner, Burkhard; Lemm, Margit; Fichtner, Iduna

doi:10.1002/jps.22001

Cited by 26 publications

(16 citation statements)

References 34 publications

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“…8,9,[15][16][17][18] Therefore, we assessed the transfection efficiency of pDNA into MDCK-I and MDCK-II cells using cationic liposomes (charge ratio at 1.0 : 2.3) under mechanical agitation. The expression levels of luciferase in both MDCK-I and MDCK-II cells were significantly high when the cells were agitated during transfection (Fig.…”

Section: Evaluation Of Cationic Liposome/pdna Complex Transport Acrosmentioning

confidence: 99%

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Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells

Kono

Iwasaki

Matsuoka

et al. 2016

Biological & Pharmaceutical Bulletin

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To develop an effective oral delivery system for plasmid DNA (pDNA) using cationic liposomes, it is necessary to clarify the characteristics of uptake and transport of cationic liposome/pDNA complexes into the intestinal epithelium. In particular, evaluation of the involvement of an unstirred water layer (UWL), which is a considerable permeability barrier, in cationic liposome transport is very important. Here, we investigated the effects of a UWL on the transfection efficiency of cationic liposome/pDNA complexes into a Caco-2 cell monolayer. When Caco-2 cells were transfected with cationic liposome/pDNA complexes in shaking cultures to reduce the thickness of the UWL, gene expression was significantly higher in Caco-2 cells compared with static cultures. We also found that this enhancement of gene expression by shaking was not attributable to activation of transcription factors such as activator protein-1 and nuclear factor-kappaB (NF-κB). In addition, the increase in gene expression by mechanical agitation was observed at all charge ratios (1.5, 2.3, 3.1, 4.5) of cationic liposome/pDNA complexes. Transport experiments using Transwells demonstrated that mechanical agitation increased the uptake of cationic liposome/pDNA complexes by Caco-2 cells, whereas transport of the complexes across a Caco-2 cell monolayer did not occurr. Moreover, the augmentation of the gene expression of cationic liposome/pDNA complexes by shaking was observed in Madin-Darby canine kidney cells. These results indicate that a UWL greatly affects the uptake and transfection efficiency of cationic liposome/pDNA complexes into an epithelial monolayer in vitro.

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Section: Evaluation Of Cationic Liposome/pdna Complex Transport Acrosmentioning

confidence: 99%

“…13) Therefore, it is very important to elucidate how a UWL affects the uptake and transport of cationic liposomes/pDNA complexes into epithelial cells in experiments performed in vitro. The characteristics or mechanisms of nanoparticle transport in epithelial cells have been reported, [14][15][16][17][18] whereas few reports have addressed the effect of UWLs.…”

mentioning

confidence: 99%

Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells

Kono

Iwasaki

Matsuoka

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Preclinical experiments further demonstrated that alkylphospholipids, if used in liposomal form, are able to abolish multi drug resistance in human breast cancer xenografts (Zeisig et al, 2004) and inhibit metastasis if combined with an aggregation inhibitor inside liposomes in murine syngene (Wenzel et al, 2010) and human xenograft breast cancer models (Wenzel et al, 2009). Perifosine in combination with dioleylphosphoethanolamine, as a component of the liposome bilayer, also enhances transport of drugs across the blood brain barrier and in this way improves the treatment of intracerebral tumours and metastases (Orthmann et al, 2010). Miltefosine was also tested as an alternative approach for the treatment of patients with progressive cutaneous lesions from breast cancer in Phase I and II studies, which indicated that Miltefosine (either used alone or in conjunction with other therapies for distant metastases) is an effective and tolerable local treatment for cutaneous breast cancer (Clive et al, 1999;Unger & Eibl, 1991).…”

Section: Alkylphospholipids In Clinical Trialsmentioning

confidence: 99%

Interaction of Alkylphospholipid Formulations with Breast Cancer Cells in the Context of Anticancer Drug Development

Koklic¹,

Podlipec²,

Mravljak³

et al. 2011

Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis

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“…A positive correlation between membrane fluidity in the upper part of the membrane bilayer and transcytosis was found [6]. Similarly, it has been suggested that also polyunsaturated fatty acids influence transendothelial transport of cortisol across an MDCK barrier by inducing changes in membrane fluidity and somehow affecting tight junction integrity [13].…”

Section: Introductionmentioning

confidence: 99%

“…Increased transendothelial delivery was observed for liposomes containing both DOPE and perifosine as well as for liposomes containing only perifosine [6]. This suggests that either perifosine influences destabilization of endosomal memebranes to a much greater extent than DOPE or that endocytosis with destabilization of endosomal membrane might not be the primary mode of transendothelial delivery.…”

Section: Introductionmentioning

confidence: 99%

Lysolipid containing liposomes for transendothelial drug delivery

Koklic

trancar

2012

BMC Res Notes

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BackgroundDesigning efficient 'vectors', to deliver therapeutics across endothelial barriers, in a controlled manner, remains one of the key goals of drug development. Recently, transcytosis of liposome encapsulated fluorescence marker calcein across a tight cell barrier was studied. The most efficient liposomes were found to be liposomes containing sufficient amount of alkyl phospholipid (APL) perifosine. APLs have similar structure as lysophosphatidyl choline (LPC), since APLs were synthesized as metabolically stable analogues of LPC, which increases endothelial permeability directly by inducing endothelial cell contraction, resulting in formation of gaps between endothelial cells. Since one of the unique properties of lysolipid, containing liposomal formulations is dynamic equilibrium of lysolipids, which are distributed among liposomes, micelles, and free form, such liposomes represent a reservoir of free lysolipids. On the other hand lysolipid containing liposomes also represent a reservoir of an encapsulated hydrophilic drug.Presentation of the hypothesisWe hypothesize that free lysolipids, with highest concentration in vicinity of drug carrying liposomes, compromise endothelial integrity, primarily where concentrations of liposomes is the highest, in a similar manner as LPC, by formation of gaps between endothelial cells. Liposome encapsulated drug, which leaks from liposomes, due to liposome destabilization, caused by lysolipid depletion, can therefore be efficiently transported across the locally compromised endothelial barrier.Testing the hypothesisThis hypothesis could be verified: by measuring binding of perifosine and other lysolipids to albumin and to lysophospholipid receptor (LPL-R) group; formation of stress fibers and subsequent cell contraction; activation of RhoA, and endothelial barrier dysfunction; by a synthesis of other LPC analogues with high critical micellar concentration and measuring their effect on transendothelial permeability in presence and absence of albumin.Implications of the hypothesisWe propose that lysolipid containing liposomal formulations might be used as nonspecific transendothelial transport vector, since leakage of liposome encapsulated active drug occurs simultaneously with the release of the lysolipids. The concentration of the active drug is therefore expected to be the highest at the site of compromised endothelial barrier. By appropriate choice of the lysolipids an endothelial barrier would stay open only for a short time. Use of such liposomes would potentially maximize the delivery of the drug while limiting the passage of toxic substances and pathogens across the endothelial barrier. Combining lysolipid containing liposomes with superparamagnetic iron oxide nanoparticles or a targeting ligand might be required to efficiently localize drug delivery to a disease affected tissue and to avoid endothelial disruption over the entire body.

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Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model

Cited by 26 publications

References 34 publications

Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells

Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells

Interaction of Alkylphospholipid Formulations with Breast Cancer Cells in the Context of Anticancer Drug Development

Lysolipid containing liposomes for transendothelial drug delivery

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