A liposomal formulation of doxorubicin, composed of hexadecylphosphocholine (HePC): physicochemical characterization and cytotoxic activity against human cancer cell lines.

The overall goal of this study was to prepare a novel liposomal formulation of doxorubicin, composed of hexadecylphosphocholine (HePC), as a combined formulation and to study its activity against cancer cells and peripheral blood mononuclear cells (PBMCs), in terms of efficacy and toxicity. Liposomes composed of HePC/egg phosphatidylcholine/stearylamine (HePC/EPC/SA) 10:10:0.1 (molar ratio) (1) and EPC/SA 10:0.1 (molar ratio) (2) were prepared and doxorubicin was encapsulated using the pH gradient method. Determination of lipids and doxorubicin has been achieved by high-performance thin-layer chromatography coupled with a flame-ionization detector. Prepared liposomes were characterized for their size distribution and their zeta-potential at each step of the preparation procedure. In vitro release studies have been evaluated in buffer and culture medium at 25 and 37 degrees C for 24 hours period. Liposomal formulations, free doxorubicin and HePC were tested against cancer cell lines and PBMCs, using sulforhodamine B (SRB) assay. Doxorubicin was encapsulated into the liposomes 1 and 2 at a drug to lipid molar ratio of 1.08 and 0.77, respectively, with an entrapping efficiency almost 100% in both cases. Doxorubicin was retained into liposome 1 up to 70% at 25 degrees C in TES, while up to 80% was released from 1 when liposomes were incubated at 37 degrees C either in culture medium or in the TES buffer at 24 hours. The activity of doxorubicin was retained or slightly improved when entrapped into liposomes 1 and 2, while liposomal formulation 1 encapsulating doxorubicin was found to be less toxic against normal cells (PBMCs). The combination of HePC and doxorubicin in one combined formulations justified as an improvement of the therapeutic index (TI) of doxorubicin in terms of efficacy and toxicity.

Doxorubicin-PAMAM dendrimer complex attached to liposomes: cytotoxic studies against human cancer cell lines.

Liposomes composed of HePC:EPC:SA 10:10:0.1 (molar ratio) (1) and EPC:SA 10:0.1 (molar ratio) (2) were prepared and were used for incorporating the doxorubicin-PAMAM complex (3:1 molar ratio) (3). The doxorubicin-PAMAM complex was attached to liposomes and the incorporation efficiency was 91 and 95% for 1 and 2, respectively. The incorporation efficiency for doxorubicin into PAMAM was almost 97% while doxorubicin to PAMAM molar ratio was 3.56+/-0.04. The release rate of doxorubicin as doxorubicin-PAMAM complex from liposomes 1 and 2 and from the complex 3, was studied using buffers and 50% RPMI cell culture medium at 37 and 25 degrees C. The low release rate of doxorubicin as well as the high incorporation efficiency of doxorubicin-PAMAM complex into liposomes are considered as beneficial factors concerning the activity of doxorubicin. The cytotoxic activity of the liposomal formulation 1 incorporating doxorubicin-PAMAM complex, based on doxorubicin activity, was compared to that of 2 incorporating doxorubicin-PAMAM complex and to that of 3. The results showed that complex 1 was the most active formulation against all cancer cell lines compared to that of 2 and 3. Liposomal formulations composed of lipids and of a drug-dendrimer complex could be characterized as modulatory liposomal controlled release system (MLCRS), and could provide benefits to the delivery of drugs and modulate their release.

Rapid alterations of serum fatty acids with the intravenous administration of an arachidonate solution.

Polyunsaturated fatty acids (PUFAs) have been shown to possess a considerable anti-tumor and anti-bacterial effect in vitro. In an attempt to achieve serum concentrations of these acids similar to those applied in vitro, a solution of ethyl ester of arachidonic acid (AA) was administered intravenously at 25 mg/kg within 10 min in six male rabbits. Blood samples were collected before and 60 min after infusion from catheters inserted in the hepatic veins and in the carotid artery. Analysis of serum fatty acids was performed by gas chromatography mass spectrometry. Elevated concentrations of elongated fatty acids were detected in the hepatic veins after infusion. Mean concentrations of arachidonate in the hepatic veins and the carotid arteries after infusion of AA were 2.77 and 3.73 microM, respectively. It is concluded that the intravenous administration of a solution of AA might result in increased hepatic biosynthesis of serum saturated and unsaturated fatty acids of elongated carbon chains. The increasing interest for the application of PUFAs in therapeutics renders further study mandatory to clarify the significance of these findings.