Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

The changing landscape of cancer drug discovery: a challenge to the medicinal chemist of tomorrow

noSince the development of the first cytotoxic agents, synthetic organic chemistry has advanced enormously. The synthetic and medicinal chemists of today are at the centre of drug development and are involved in most, if not all, processes of drug discovery. Recent decreases in government funding and reformed educational policies could, however, seriously impact on drug discovery initiatives worldwide. Not only could these changes result in fewer scientific breakthroughs, but they could also negatively affect the training of our next generation of medicinal chemists

Statistical Analysis of Solar Events Associated with Storm Sudden Commencements over One Year of Solar Maximum During Cycle 23: Propagation from the Sun to the Earth and Effects

International audienceTaking the 32 storm sudden commencements (SSCs) listed by the International Service of Geomagnetic Indices (ISGI) of the Observatory de l’Ebre during 2002 (solar activity maximum in Cycle 23) as a starting point, we performed a multi-criterion analysis based on observations (propagation time, velocity comparisons, sense of the magnetic field rotation, radio waves) to associate them with solar sources, identified their effects in the interplanetary medium, and looked at the response of the terrestrial ionized and neutral environment. We find that 28 SSCs can be related to 44 coronal mass ejections (CMEs), 15 with a unique CME and 13 with a series of multiple CMEs, among which 19 (68%) involved halo CMEs. Twelve of the 19 fastest CMEs with speeds greater than 1000 km s−1 are halo CMEs. For the 44 CMEs, including 21 halo CMEs, the corresponding X-ray flare classes are: 3 X-class, 19 M-class, and 22 C-class flares. The probability for an SSC to occur is 75% if the CME is a halo CME. Among the 500, or even more, front-side, non-halo CMEs recorded in 2002, only 23 could be the source of an SSC, i.e. 5%. The complex interactions between two (or more) CMEs and the modification of their trajectories have been examined using joint white-light and multiple-wavelength radio observations. The detection of long-lasting type IV bursts observed at metric–hectometric wavelengths is a very useful criterion for the CME–SSC events association. The events associated with the most depressed Dst values are also associated with type IV radio bursts. The four SSCs associated with a single shock at L1 correspond to four radio events exhibiting characteristics different from type IV radio bursts. The solar-wind structures at L1 after the 32 SSCs are 12 magnetic clouds (MCs), 6 interplanetary coronal mass ejections (ICMEs) without an MC structure, 4 miscellaneous structures, which cannot unambiguously be classified as ICMEs, 5 corotating or stream interaction regions (CIRs/SIRs), one CIR caused two SSCs, and 4 shock events; note than one CIR caused two SSCs. The 11 MCs listed in 3 or more MC catalogs covering the year 2002 are associated with SSCs. For the three most intense geomagnetic storms (based on Dst minima) related to MCs, we note two sudden increases of the Dst, at the arrival of the sheath and the arrival of the MC itself. In terms of geoeffectiveness, the relation between the CME speed and the magnetic-storm intensity, as characterized using the Dst magnetic index, is very complex, but generally CMEs with velocities at the Sun larger than 1000 km s−1 have larger probabilities to trigger moderate or intense storms. The most geoeffective events are MCs, since 92% of them trigger moderate or intense storms, followed by ICMEs (33%). At best, CIRs/SIRs only cause weak storms. We show that these geoeffective events (ICMEs or MCs) trigger an increased and combined auroral kilometric radiation (AKR) and non-thermal continuum (NTC) wave activity in the magnetosphere, an enhanced convection in the ionosphere, and a stronger response in the thermosphere. However, this trend does not appear clearly in the coupling functions, which exhibit relatively weak correlations between the solar-wind energy input and the amplitude of various geomagnetic indices, whereas the role of the southward component of the solar-wind magnetic field is confirmed. Some saturation appears for Dst values <−100 nT on the integrated values of the polar and auroral indices