Erufosine, a novel alkylphosphocholine, induces apoptosis in CLL through a caspase-dependent pathway.

The alkylphosphocholine (APC) erufosine is a synthetic phospholipid analogue with antineoplastic activity. APC are known to interact with lipid metabolism and modulate cellular signaling pathways, particularly the phosphorylation of Akt. Here, in primary CLL cells induction of apoptosis was detected with an IC50 of 22muM whereas healthy donor PBMC were less sensitive towards erufosine.

Quantification of erufosine, the first intravenously applicable alkylphosphocholine, in human plasma by isotope dilution liquid chromatography-tandem mass spectrometry using a deuterated internal standard.

A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of erucylphosphohomocholine (erufosine, ErPC(3)) in pharmacokinetic studies. Nine-fold deuterated ErPC(3) was used as the internal standard. Following protein precipitation, reversed phase chromatography was performed.

In vitro characterization of phosphatidylglyceroglycerol-based thermosensitive liposomes with encapsulated 1H MR T1-shortening gadodiamide.

Thermosensitive liposomes (TSL) with encapsulated proton (1H) magnetic resonance (MR) contrast agents have been proposed for noninvasive online temperature monitoring during tumor treatment using chemotherapy combined with hyperthermia (HT). The technique exploits the fact that water exchange between the TSL interior and exterior is increased and/or the encapsulated 1H MR contrast agent is released near the gel-to-liquid crystalline phase transition temperature (Tm) of TSL and thus shortens the 1H MR relaxation time of tissue. In this work, newly developed, phosphatidylglyceroglycerol (DPPGOG)-based TSL with encapsulated 1H MR longitudinal relaxation time (T1)-shortening gadodiamide (Gd-DTPA-BMA) were characterized in vitro by measuring the temperature dependence of the T1 of these gadodiamide-containing DPPGOG-TSL samples between 30 and 50 degrees C.

Dual role of hexadecylphosphocholine (miltefosine) in thermosensitive liposomes: active ingredient and mediator of drug release.

Lysolipid-based thermosensitive liposomes have been successfully introduced as efficient drug delivery system with fast drug release upon heat treatment. Hexadecylphosphocholine (HePC) is structurally related to 1-palmitoyl-2-lyso-sn-glycero-3-phosphocholine (P-lyso-PC) but chemically and metabolically more stable, thereby offering strong antineoplastic, antiprotozoal and antifungal activity. We investigated the properties of HePC in low temperature sensitive (LTSL) and high temperature sensitive liposomes (HTSL) based on 1,2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol (DPPGOG).

Erufosine, a novel alkylphosphocholine, in acute myeloid leukemia: single activity and combination with other antileukemic drugs.

Purpose: Alkylphosphocholines represent a new class of cytostatic drugs with a novel mode of action. Erufosine (ErPC3), the first compound of this class that can be administered intravenously, has recently been shown to be active against human tumor and leukemic cell lines.

Methods: In order to evaluate the antileukemic potential of ErPC3 in acute myeloid leukemia (AML) the lethal concentration 50% (LC 50) was determined using WST-1 assay.

Structural variation of cationic lipids: minimum requirement for improved oligonucleotide delivery into cells.

In vivo transfection efficiency (TE) using cationic liposome/oligonucleotide (ODN) complexes is often hampered by interactions with serum components. Novel cationic lipids with different hydroxyethyl or dihydroxypropyl ammonium backbones, esterified hydrocarbon chains and hydroxy substituents have been synthesized and applied in cationic liposome formulations with and without the helper lipid DOPE (1:1, m/m). Their properties for cellular ODN delivery were determined using fluorescently labeled ODNs (F-ODNs).

Novel temperature-sensitive liposomes with prolonged circulation time.

Hyperthermia increases the efficiency of various chemotherapeutic drugs and is administered as an adjunct to chemotherapy for the treatment of cancer patients. The temperature-dependent effect can be strongly increased by the use of temperature-sensitive liposomes in combination with regional hyperthermia, which specifically releases the entrapped drug in the heated tumor tissue. The novel lipid 1.