1-2-dioleoyloxy-3-(trimethylammonium)propane and dimyristoylphosphatidylglycerol

Topics: Dimyristoylphosphatidylcholine; Fatty Acids, Monounsaturated; Lipid Bilayers; Molecular Conformation; Molecular Docking Simulation; Phase Transition; Phosphatidylglycerols; Quaternary Ammonium Compounds; Temperature; Warfarin

The effects of a lipid composition on the physico-chemical and technological properties of a multidrug carrier (MDC) containing both gemcitabine (GEM) and tamoxifen (TMX), as well as its in vitro antitumoral activity on different breast cancer cell lines, were investigated. In particular, the following three different liposomal formulations were prepared: DPPC/Chol/DSPE-mPEG2000 (6:3:1 molar ratio, formulation A), DPPC/Chol/DOTAP (6:3:1 molar ratio, formulation B) and DPPC/Chol/DPPG (6:3:1 molar ratio, formulation C). The colloidal systems were obtained by the TLE technique and the extrusion process allowed us to obtain vesicles having mean sizes of 150-200 nm, while the surface charges varied between 50 mV and -30 mV. Formulation A showed the best encapsulation efficiency between the two compounds and the presence of TMX influenced the release profile of GEM (hydrophilic compound) as a consequence of its effect on the fluidity of the bilayer. An MDC of formulation A was used to effectuate the in vitro cytotoxicity experiments (MTT-test) on MCF-7 and T47D cells. The liposomal MDC provided the best results with respect to the single drug tested in the free form or entrapped in the same liposomal formulation. The CLSM experiments showed a great degree of cell interaction of liposomal MDC after just 6h.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Cholesterol; Colloids; Deoxycytidine; Dose-Response Relationship, Drug; Drug Compounding; Fatty Acids, Monounsaturated; Female; Gemcitabine; Humans; Kinetics; Lipids; Liposomes; Particle Size; Phosphatidylethanolamines; Phosphatidylglycerols; Polyethylene Glycols; Quaternary Ammonium Compounds; Selective Estrogen Receptor Modulators; Solubility; Tamoxifen; Technology, Pharmaceutical

Lipid monolayers have been shown to represent a powerful tool in studying mechanical and thermodynamic properties of lipid membranes as well as their interaction with proteins. Using Einstein's theory of fluctuations we here demonstrate that an experimentally derived linear relationship both between transition entropy S and area A as well as between transition entropy and charge q implies a linear relationships between compressibility κT, heat capacity cπ, thermal expansion coefficient αT, and electric capacity CT. We demonstrate that these couplings have strong predictive power as they allow calculating electrical and thermal properties from mechanical measurements. The precision of the prediction increases as the critical point TC is approached.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Algorithms; Biophysics; Calorimetry; Dimyristoylphosphatidylcholine; Fatty Acids, Monounsaturated; Hot Temperature; Lipids; Membranes; Phosphatidylglycerols; Phospholipids; Quaternary Ammonium Compounds; Reproducibility of Results; Temperature