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Jan A A M Kamps

Publications and source records attributed to Jan A A M Kamps.

16 recordsLinked to original sources
PubMed2007

Zeta-potentials of alginate-PLL capsules: a predictive measure for biocompatibility?

Alginate-poly-L-lysine (PLL) microencapsulation of cells is a promising approach to prevent rejection in the absence of immunosuppression. Clinical application, however, is hampered by insufficient insight in factors influencing biocompatibility of the capsules. By now, it has been accepted that not only the chemical composition of the materials applied but also other factors contribute to bioincompatibility. The zeta-potential serves as a measure for the electrical charge of the surface and has been shown to be a predictive value for the interfacial reactions between the biomaterial and the surrounding tissue in other applications. In the present study, we have assessed the streaming potential of alginate-PLL capsules composed of either low-, intermediate-, or high-guluronic (G) alginate to calculate the zeta-potential. The zeta-potentials of the capsules were compared to the biological response against the capsules at 4 weeks after implantation in the rat. We show that high-G and low-G alginates provoke a more severe response in the rat than capsules prepared of intermediate-G alginate. This correlates with a higher zeta-potential of the high-G and low-G alginates and by a change in zeta-potential at lower pH. These lower pH-levels are common directly after implantation as the consequence of a host-response associated with mandatory surgery. Our results suggest that we should not only consider the capsule properties under physiological circumstances to explain bioincompatibility but also the capsule features during common pathophysiological situations.

Alginates↗
PubMed2005

Interaction of targeted liposomes with primary cultured hepatic stellate cells: Involvement of multiple receptor systems.

BACKGROUND/AIMS: In designing a versatile liposomal drug carrier to hepatic stellate cells (HSC), the interaction of mannose 6-phosphate human serum albumin (M6P-HSA) liposomes with cultured cells was studied. METHODS: M6P-HSA was covalently coupled to the liposomal surface and the uptake and binding of 3H-labelled M6P-HSA liposomes by primary rat HSC and liver endothelial cells was determined. The targeting ability of M6P-HSA liposomes to HSC was tested in bile duct ligated rats using immunohistochemical methods. RESULTS: The association of M6P-HSA liposomes with HSC was 4-fold higher than of control liposomes. An excess of M6P-HSA inhibited this association by 58%, indicating M6P receptor specificity. The scavenger receptor competitor polyinosinic acid abolished association of M6P-HSA liposomes with HSC. M6P-HSA liposomes also amply associated with endothelial cells, which abundantly express scavenger receptors. Endocytosis of M6P-HSA liposomes by HSC was temperature dependent and could be inhibited by monensin. In the fibrotic liver M6P-HSA liposomes co-localised with HSC. CONCLUSIONS: Coupling of M6P-HSA to liposomes strongly increases the in vitro uptake of these liposomes by HSC and endothelial cells. Both the mannose 6-phosphate receptor and the scavenger receptors are involved in the uptake process. M6P-HSA liposomes are potential drug carriers to HSC in the fibrotic liver.

Animals↗
PubMed2005

The role of apolipoprotein E in the elimination of liposomes from blood by hepatocytes in the mouse.

We evaluated the role of apolipoprotein E (apoE) in the clearance of neutral and negatively charged liposomes by hepatocytes in apoE-deficient mice. Negatively charged liposomes were cleared at identical rates in apoE-deficient and wild-type mice; neutral liposomes were cleared at a 3.6-fold slower rate in apoE-deficient mice. ApoE deficiency did not affect hepatic uptake of negatively charged liposomes but lowered that of neutral liposomes >5-fold. Hepatocyte uptake of neutral liposomes was reduced >20-fold in apoE-deficient mice; that of negatively charged liposomes remained unchanged. We conclude that uptake of neutral liposomes by hepatocytes is nearly exclusively apoE-mediated.

Animals↗
PubMed2005

Kupffer cell depletion with liposomal clodronate prevents suppression of Ntcp expression in endotoxin-treated rats.

BACKGROUND/AIMS: In sepsis-associated cholestasis, expression of many genes involved in bile acid transport, including Ntcp, is suppressed by cytokines. Kupffer cells (KC) are an important source of cytokines in sepsis. To assess the consequences of KC depletion on hepatic Ntcp expression in endotoxemic rats. METHODS: Sprague-Dawley rats received liposomal clodronate (CLO) or vehicle (PBS) to deplete KC prior to lipopolysaccharide (LPS) exposure. Plasma and liver samples were taken 1 and 16 h after LPS exposure. RESULTS: Complete CLO-depletion of KC by was demonstrated by immunohistochemistry. Hepatic gene expression of IL-1beta and TNFalpha as well as TNFalpha plasma levels in CLO/LPS-injected animals were significantly reduced to a mean of 41, 36 and 23% of controls injected with LPS only. Ntcp RNA- and protein expression was significantly higher whereas plasma bile salt concentration was lower in CLO/LPS animals vs. animals injected with LPS only. Binding activity of transcription factors RXR:RAR and HNF1alpha was decreased in LPS only controls but preserved in CLO/LPS treated animals. CONCLUSIONS: Clodronate-depletion of KC blocks cytokine-mediated Ntcp suppression upon endotoxin exposure. KC may represent pharmacological targets for treatment of sepsis-associated cholestasis.

Animals↗
PubMed2005

Cell-specific targeting of lipid-based carriers for ODN and DNA.

It is well recognized that there is an urgent need for non-toxic systemically applicable vectors for biologically active nucleotides to fully exploit the current potential of molecular medicine in gene therapy. Cell-specific targeting of non-viral lipid-based carriers for ODN and DNA is a prerequisite to attain the concentration of nucleic acids required for therapeutic efficacy in the target tissue. In this review we will address the most promising approaches to selective targeting of liposomal nucleic acid carriers in vivo. In addition, the routes of entry and intracellular processing of these carrier systems are discussed as well as physiological factors potentially interfering with the biological and/or therapeutic activity of their nucleotide pay-load.

Active Transport, Cell Nucleus↗
PubMed2005

Liposome opsonization.

Adsorption of serum proteins to the liposomal surface plays a critical role in the clearance of liposomes from the blood circulation. In this review, we will discuss the role of the liposomal opsonins proposed so far in liposome clearance. Additional, related topics that will be addressed are the cell-surface receptors that might be involved in liposome elimination from the blood compartment and the effect of poly(ethylene glycol) (PEG) modification on prevention of liposome opsonization.

Animals↗
PubMed2005

Molecular pathways of endothelial cell activation for (targeted) pharmacological intervention of chronic inflammatory diseases.

In chronic inflammatory conditions, endothelial cells actively recruit immune cells from the circulation into the underlying tissue and participate in angiogenesis to support the continuous demand for oxygen and nutrients. They do so in response to activation by cytokines and growth factors such as tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL-1), vascular endothelial growth factor (VEGF), and fibroblast growth factors (FGFs). Receptor triggering initiates intracellular signal transduction leading to activation of nuclear factor kappaB (NFkappaB), mitogen activated protein kinase (MAPK) activity, and nitric oxide and reactive oxygen species production, among others. As a result, adhesion molecules, cytokines and chemokines, and a variety of other genes are being expressed that mediate and control the inflammatory process. In recent years, different classes of drugs have been developed that interfere with selected enzymes involved in the intracellular signalling cascades. In endothelial cell cultures, they exert potent inhibitory effects on the expression of genes, while several studies also report on in vivo effectiveness to confine the inflammatory responses. To prevent undesired toxicity and to improve drug behaviour and efficacy, drug carrier systems have been developed that selectively deliver the therapeutics into the activated endothelial cells. The above subjects are recapitulated to give an overview on the status of development of endothelial cell directed therapeutic strategies to pharmacologically interfere with chronic inflammatory diseases.

Animals↗
PubMed2004

Optimized targeting of polyethylene glycol-stabilized anti-intercellular adhesion molecule 1 oligonucleotide/lipid particles to liver sinusoidal endothelial cells.

We prepared polyethylene glycol (PEG)-stabilized antisense oligonucleotide (ODN)/lipid particles from a lipid mixture including the positively charged amphiphile 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and anti-intercellular adhesion molecule 1 (ICAM-1) antisense ODN by an extrusion method in the presence of 40% ethanol. These particles were targeted to scavenger receptors on liver endothelial cells by means of covalently coupled polyanionized albumin. Two types of such targeted particles were prepared, one with the albumin coupled to a maleimide group attached to the particle's lipid bilayer and the other with the protein coupled to a maleimide group attached at the distal end of added bilayer-anchored PEG chains. Upon intravenous injection, the ODN particles with bilayer-coupled albumin were cleared from the blood circulation at the same low rate as untargeted particles (<5% in 30 min). By contrast, the distal-end coupled particles were very rapidly cleared from the blood and preferentially taken up by the endothelial cells of the hepatic sinusoid (55% of injected dose after 30 min). Despite this substantial endothelial targeting, no consistent inhibition of ICAM-1 expression could be demonstrated in this cell type, either in vivo or in vitro. However, in J774 cells that also express scavenger receptors and ICAM-1, significant down-regulation of ICAM-1 mRNA was achieved with distal-end targeted lipid particles, as determined with real-time RT-PCR. It is concluded that massive delivery of ODN to cell types that express scavenger receptors can be achieved if lipid particles are provided with negatively charged albumin distally attached to bilayer anchored PEG chains.

Animals↗
PubMed2004

Stabilized lipid coated lipoplexes for the delivery of antisense oligonucleotides to liver endothelial cells in vitro and in vivo.

We report on the preparation and in vivo/in vitro disposition of antisense ODN encapsulating coated cationic lipoplexes (CCLs), prepared by a procedure essentially developed by Stuart and Allen (Stuart, D.D. and Allen, T.M. (2000) "A new liposomal formulation for antisense oligodeoxynucleotides with small size, high incorporation efficiency and good stability", Biochim. Biophys. Acta 1463, pp. 219-229). The behavior of untargeted CCLs was compared with CCLs that were targeted to scavenger receptors on liver endothelial cells by covalent coupling of the poly-anion aconitylated human serum albumin (Aco-HSA) to the particle surface. By means of cryo transmission electron microscopy (cryo-TEM) particles of high electron density could be distinguished from electron-translucent particles, representing high and low ODN encapsulation, respectively. The two populations were separated by sucrose density gradient centrifugation. Upon injection into rats, the untargeted particles showed long circulating properties with a half-life of >10 h. These untargeted CCLs barely bound to liver endothelial cells in vitro while Aco-HSA CCLs massively and specifically interacted with scavenger receptors on these cells. With J774 cells, a macrophage cell line expressing scavenger receptors, downregulation of ICAM-1 mRNA levels was achieved when the ODN was specifically delivered by Aco-HSA targeted CCLs.

Animals↗
PubMed2003

The influence of repeated injections on pharmacokinetics and biodistribution of different types of sterically stabilized immunoliposomes.

Sterically stabilized immunoliposomes (IL) with diameters of about 135 nm carrying mouse IgG, either coupled directly to the liposome surface, or linked to the terminal ends of grafted poly(ethylene glycol) (PEG) chains by a recently described conjugation procedure (Cyanur-PEG-PE), were intravenously injected into rats and the elimination kinetics and biodistribution were determined and compared with control liposomes. The amounts of conjugated antibodies were about 30 microg/micromol total lipid for all IL. In naive rats, plain pegylated liposomes displayed the longest blood circulation time, whereas the terminal-coupled IL exhibited the fastest elimination. Liposomes containing the underivatized anchor molecules circulate nearly as long as plain pegylated liposomes, indicating that the fast elimination of the IL can be attributed to the presence of antibodies.A second injection of identical liposomes 14 days after the first injection had a considerable influence on the pharmacokinetic parameters of the liposomes. The circulation time of plain pegylated liposomes drastically dropped by half and their uptake by the liver increased concomitantly, indicating that the PEG, upon repeated injection, ceases to function as an efficient barrier reducing opsonization and/or immune reactions. The circulation time of conventional IL was moderately reduced upon a second injection, whereas that of the terminally coupled IL was nearly unaffected. These differences among the IL demonstrate that the pharmacokinetic behavior of IL is strongly dependent on the antibody conjugation site on the liposome. The observed effects of repeated injections were similar for liposomes of 90-nm diameter. The phenomena described may have important implications for the repeated application of IL as drug carriers.

Animals↗
PubMed2003

Interaction of differently designed immunoliposomes with colon cancer cells and Kupffer cells. An in vitro comparison.

PURPOSE: Evaluate the effectiveness of distal-end coupling of a tumor-specific antibody to liposomal polyethylene glycol (PEG) chains to improve target binding and reduce interference by macrophage uptake. METHODS: Monoclonal antibody CC52, specific for CC531 rat colon carcinoma, was coupled to the bilayer of PEG-liposomes (type I) or to the distal end of bilayer-anchored PEG-chains (type II). Uptake of both (radiolabeled)liposome types by CC531 cells and rat liver macrophages was determined. RESULTS: With increasing antibody density, both immunoliposome types showed increased binding to target cells, but type II liposomes displayed better target recognition than type I. Uptake by macrophages increased with antibody density for both liposome types. Lowest uptake by macrophages was found for type II liposomes at low antibody densities. Unexpectedly, not only for type I but also for type II liposomes, in which the antibody is coupled via its Fc moiety, uptake by macrophages was inhibited by aggregated IgG, indicating involvement of Fc receptors. Also polyinosinic acid, an inhibitor of scavenger receptors, reduced uptake of type II liposomes. CONCLUSION: Although distal end coupling of antibodies to bilayer-anchored PEG chains in liposomes through the Fc moiety enhances target cell binding, it does not prevent the recognition by Fc receptors on macrophages.

Animals↗
PubMed2002

Efficient intracellular delivery of 5-fluorodeoxyuridine into colon cancer cells by targeted immunoliposomes.

Immunoliposomes, liposomes with monoclonal antibodies attached, are being developed for targeting the anti-cancer drug 5-fluoro-2'-deoxyuridine (FUdR) to colon cancer cells. A monoclonal antibody against the rat colon carcinoma CC531 was covalently coupled to liposomes containing a dipalmitoylated derivative of the anti-cancer drug FUdR (FUdR-dP) as a prodrug in their bilayers. We studied the association with the tumor cells of different types of immunoliposomes varying in the position and orientation of the antibody at the liposome surface. We also assessed the in vitro anti-tumor activity of these liposomes and the mechanism by which the active drug FUdR is delivered intracellularly. Specific binding of the immunoliposomes to the tumor cells was observed. Immunoliposomes containing FUdR-dP caused a much stronger inhibition of CC531 cell growth in vitro than FUdR-dP in non-targeted liposomes. After binding to the cell surface only limited amounts of the immunoliposomes were internalized. By contrast, already within 24 h immunoliposome-incorporated FUdR-dP was hydrolyzed virtually completely to the parent drug FUdR, intracellularly. The mechanism of intracellular delivery of the drug most likely involves a selective transfer of the lipophilic prodrug from the liposomes to the cell membrane and subsequent intracellular processing. In conclusion, we developed a targeted liposomal formulation, which is able to deliver FUdR to colon carcinoma cells intracellularly with high efficiency, without the need for the cells to internalize the liposomes as such. This approach may be attractive for other lipophilic anti-cancer (pro)drugs. In this sense our system also serves as a model for the development of new lipid-based drug delivery systems for anti-cancer therapy.

Antibodies, Monoclonal↗
PubMed2002

Massive and selective delivery of lipid-coated cationic lipoplexes of oligonucleotides targeted in vivo to hepatic endothelial cells.

PURPOSE: Previously we reported on massive uptake of liposomes surface-modified with negatively charged aconitylated albumin (AcoHSA) by liver sinusoidal endothelial cells (EC) in vivo. In the present work we applied this principle for the in vivo delivery of antisense oligonucleotides (ODN) to these cells. METHODS: Anti ICAM-1 ODN was complexed with the cationic lipid DOTAP and the complex was coated by an excess of neutral lipids including a lipid-anchored poly(ethylene glycol). Aco-HSA was coupled to the coated cationic lipoplexes (CCLs). Plasma disappearance, organ and intrahepatic distribution of Aco-HSA modified CCLs were determined in rats, using [3H]-cholesteryl oleyl ether and 32P-labeled ODN as markers. RESULTS: The Aco-HSA coupled CCLs were <160 nm in size, contained 1.03+/-0.35 nmol ODN and 54+/-18 microg Aco-HSA per micromol total lipid. These CCLs were rapidly eliminated from plasma, about 60% the injected dose of 3H- or 32P-label being recovered in the liver after 30 min. Within the liver, the EC accounted for two thirds of total liver uptake. Control non-targeted CCLs were eliminated very slowly: after 30 min still >90% of the particles was in the blood. CONCLUSIONS: Our results demonstrate efficient targeting of antisense ODN to EC in vivo, employing plasma-stable coated cationic lipoplexes, surface modified with negatively charged albumin. 40% of the injected ODN was delivered to the target cells within 30 min.

Aconitic Acid↗
PubMedDate not supplied

Interference of macrophages with immunotargeting of liposomes.

We investigated the binding, uptake and intracellular degradation of immunoliposomes by isolated rat liver macrophages in vitro. Immunoliposomes were prepared either by coupling a randomly thiolated anti-CC531 rat colon adenocarcinoma monoclonal antibody to bilayer-incorporated MPB-PE by means of a thioether linkage or by attaching it through its Fc moiety to the distal terminus of hydrazide-modified PEG-DSPE. The two immunoliposome preparations clearly differ in their interaction with the tumor target cells, as well as with the macrophages. At comparable antibody densities both cell types show 1.5-2-fold higher levels of association for the Hz-PEG-immunoliposomes than for the MPB-PEG-immunoliposomes. We provide evidence that immunoliposome macrophage-interaction is both Fc-receptor and scavenger receptor mediated to about equal extents. At low antibody density the hydrazide immunoliposomes favor interaction with the tumor cells to that with macrophages. At higher antibody densities, on the other hand, interaction of these liposomes with the macrophages is increasingly favored, mostly due to enhanced scavenger receptor mediated uptake. The rate of intracellular degradation of (immuno)liposomes internalized by liver macrophages is barely influenced by the presence of either PEG or immunoglobulins on the liposomal surface.

Animals↗