Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model

Jantscheff, Peter; Ziroli, Vittorio; Esser, N.; Graeser, Ralph; Kluth, Jessica; Sukolinskaya, Alena; Taylor, Lenka A.; Unger, Clemens; Massing, Ulrich

doi:10.1007/s10585-009-9288-1

Cited by 30 publications

(26 citation statements)

References 49 publications

(71 reference statements)

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“…Recently, a strong antimetastatic effect of empty liposomes consisting only of hydrogenated PC and cholesterol was reported in two different orthotopic pancreatic tumor models in mice (AsPC1, LNCaP) while the growth of the primary tumors was not affected [35,36]. Investigating the underlying mode of action revealed that the PC degradation product, namely hydrogenated lysoPC, is most likely pivotal for the observed effect.…”

Section: Introductionmentioning

confidence: 99%

Health effects of dietary phospholipids

Küllenberg¹,

Taylor

Schneider³

et al. 2012

Lipids Health Dis

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435

305

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Beneficial effects of dietary phospholipids (PLs) have been mentioned since the early 1900's in relation to different illnesses and symptoms, e.g. coronary heart disease, inflammation or cancer. This article gives a summary of the most common therapeutic uses of dietary PLs to provide an overview of their approved and proposed benefits; and to identify further investigational needs.From the majority of the studies it became evident that dietary PLs have a positive impact in several diseases, apparently without severe side effects. Furthermore, they were shown to reduce side effects of some drugs. Both effects can partially be explained by the fact that PL are highly effective in delivering their fatty acid (FA) residues for incorporation into the membranes of cells involved in different diseases, e.g. immune or cancer cells. The altered membrane composition is assumed to have effects on the activity of membrane proteins (e.g. receptors) by affecting the microstructure of membranes and, therefore, the characteristics of the cellular membrane, e.g. of lipid rafts, or by influencing the biosynthesis of FA derived lipid second messengers. However, since the FAs originally bound to the applied PLs are increased in the cellular membrane after their consumption or supplementation, the FA composition of the PL and thus the type of PL is crucial for its effect. Here, we have reviewed the effects of PL from soy, egg yolk, milk and marine sources. Most studies have been performed in vitro or in animals and only limited evidence is available for the benefit of PL supplementation in humans. More research is needed to understand the impact of PL supplementation and confirm its health benefits.

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Section: Introductionmentioning

confidence: 99%

Health effects of dietary phospholipids

Küllenberg¹,

Taylor

Schneider³

et al. 2012

Lipids Health Dis

Self Cite

435

305

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show abstract

“…The results in terms of cytotoxic activity were very promising in different in vitro and in vivo studies [13][14][15][16][17]. In our previous work, in order to obtain both a physical and a chemical protection of the drug, we have synthesized and incorporated into liposomes lipophilic GEM prodrugs that were obtained by linking the N 4 -amino group with linear acyl chains of different length which enhanced drug incorporation and antitumoral activity [18,19].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-coated liposomes for active targeting of gemcitabine

Berlier

Lerda

Pozza

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

125

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The aim of this work was the preparation, characterization and preliminary evaluation of the targeting ability towards pancreatic adenocarcinoma cells of liposomes containing the gemcitabine lipophilic prodrug [4-(N)-lauroyl-gemcitabine, C12GEM]. Hyaluronic acid (HA) was selected as targeting agent since it is biodegradable, biocompatible, can be chemically modified and its cell surface receptor CD44 is overexpressed on various tumors.For this purpose, conjugates between a phospholipid, the 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and HA of two different low molecular weights 4800 Da (12 disaccharidic units) and 12000 Da (32 disaccharidic units), were prepared, characterized and introduced in the liposomes during the preparation.Different liposomal formulations were prepared and their characteristics were analyzed: size, Z potential and TEM analyses underline a difference of the HA-liposomes from the non-HA ones. In order to better understand the HA-liposome cellular localization and to evaluate their interaction with CD44 receptor, confocal microscopy studies were performed. The results demonstrate that HA facilitates the recognition of liposomes by MiaPaCa2 cells (CD44 + ) and that the uptake increases with increasing of the polymer molecular weight.Finally, the cytotoxicity of the different preparations was evaluated and data show that incorporation of C12GEM increases their cytotoxic activity and that HA-liposomes inhibit cell growth more than plain liposomes.Altogether the results demonstrate the specificity of C12GEM targeting towards CD44-overexpressing pancreatic adenocarcinoma cell line using HA as a ligand.

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“…However, the limitation of gemcitabine is its rapid inactivation by the deoxycytidine deaminase following intravenous administration, which leads to the use of innovative drug delivery systems, such as liposomes, for improving its pharmacological and biopharmaceutical properties. To overcome these limitations of gemcitabine, various types of delivery systems, including liposomes, had been studied for anticancer effects in prostate cancer 26 , lung cancer 27 and pancreatic cancer 28 .…”

Section: Introductionmentioning

confidence: 99%