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Factors affecting acoustically triggered release of drugs from polymeric micelles
No full textA custom ultrasonic exposure chamber with real-time fluorescence detection was used to measure acoustically-triggered drug release from Pluronic P-105 micelles under continuous wave (CW) or pulsed ultrasound in the frequency range of 20 to 90 kHz. The measurements were based on the decrease in fluorescence intensity when drug was transferred from the micelle core to the aqueous environment. Two fluorescent drugs were used: doxorubicin (DOX) and its paramagnetic analogue, ruboxyl (Rb). Pluronic P-105 at various concentrations in aqueous solutions was used as a micelle-forming polymer. Drug release was most efficient at 20-kHz ultrasound and dropped with increasing ultrasonic frequency despite much higher power densities. These data suggest an important role of transient cavitation in drug release. The release of DOX was higher than that of Rb due to stronger interaction and deeper insertion of Rb into the core of the micelles. Drug release was higher at lower Pluronic concentrations, which presumably resulted from higher local drug concentrations in the core of Pluronic micelles when the number of micelles was low. At constant frequency, drug release increased with increasing power density. At constant power density and for pulse duration longer than 0.1 s, peak release under pulsed ultrasound was the same as stationary release under CW ultrasound. Released drug was quickly re-encapsulated between the pulses of ultrasound, which suggests that upon leaving the sonicated volume, the non-extravasated and non-internalized drug would circulate in the encapsulated form, thus preventing unwanted drug interactions with normal tissues
Stabilization of Pluronic P-105 Micelles with an Interpenetrating Network of N,N-Diethylacrylamide
No full textN,N-Diethylacrylamide (NNDEA) was polymerized in the presence of Pluronic P-105 micelles. The polymerizations resulted in an interpenetrating network of poly(NNDEA) and P-105 that stabilized the micelles at concentrations below the critical micellar concentration of free P-105. The NNDEA was cross-linked with N,N′-bis(acryoyl)cystamine (BAC), and the degree of micellar stability was determined using dynamic light scattering and the fluorescent probe diphenylhexatriene (DPH).The increased micellar stability was not permanent and disappeared over a time period of days to weeks
DNA damage induced by micellar-delivered doxorubicin and ultrasound: comet assay study
No full textTo minimize adverse side effects of chemotherapy, we have developed a micellar drug carrier that retains hydrophobic drugs, and then releases the drug by ultrasonic stimulation. This study investigated the DNA damage induced by doxorubicin (DOX) delivered to human leukemia (HL-60) cells from pluronic P-105 micelles with and without the application of ultrasound. The comet assay was used to quantify the amount of DNA damage. No significant DNA damage was observed when the cells were treated with 0.1, 1 and 10 wt% P-105 with or without ultrasound (70 kHz, 1.3 W/cm2) for 1 h or for up to 3 h in 10 wt% P-105. However, when cells were incubated with 10 μg/ml free DOX for up to 9 h, DNA damage increased with incubation time (P=0.0011). Exposure of cells to the same concentration of DOX in the presence of 10-wt% P-105 showed no significant DNA damage for up to 9 h of incubation. However, when ultrasound was applied, a rapid and significant increase in DNA damage was observed (P=0.0001). The application of ultrasound causes the release of DOX from micelles or causes the HL-60 cells to take up the micelle encapsulated DOX. Our experiments indicated that the combination of DOX, ultrasound and pluronic P105 causes the largest DNA damage to HL-60 cells. We believe that this technique can be used for controlled drug delivery
L'integration des expatries dans leur nouveau poste : une analyse contingente et quantitative
No full textL’expatriation est une forme particulière de transfert (Feldman et Thompson, 1992; Carter, 1989). Plusieurs études (Hall, 1990; d’Iribarne, 1989) montrent que les différences inter-culturelles peuvent avoir des implications humaines et économiques importantes, à la fois pour le migrant, pour ses proches, et pour l’entreprise concernée. L’objectif de notre étude est de mettre en évidence les principaux facteurs qui influencent l’adaptation des salariés après un transfert à l’étranger. La partie empirique de la recherche a été conduite en Norvège, un des pays occidentaux où les expatriés français éprouvent le plus de difficultés à s’adapter (Billeau, 1993). Dans une première partie, nous présenterons d’abord une revue de littérature et un modèle d’analyse qui servira de base à la formulation de nos hypothèses. La seconde partie présentera la méthode utilisée, puis les résultats sont présentés et discutés dans les deux dernières parties
Eastern Germany's Transportation System: Can it Compete in Europe 1992?
No full textThe eastern German rail system is operating with one half the line network of western Germany, but approximately the same numer of employees and amount of freight carriage. The two rail systems are proportionately about the same size (Railway Lines to Area Ratio). The eastern German road network proportionately is much smaller than the western (Main Roads to Area Ratio), but transports 83% as much freight as western Germany. The inland waterway system in eastern Germany is proportionately somewhat larger than western Germany (Waterways to Area Ratio), and transports approx. the same amount of freight. In every east German modal system a substandard infrastructure handles a disproportionate amount of freight compared to the west. This indicates that Eastern Germany could be extremely efficient with a modern, state-of-the-art transportation infrastructure