fig , confocal fluorescence images of bt cells stained with mitotracker red after exposure for lohrs to dna green complexed with cdqasomes left column circular mlspdna conjugate, right column linearized mlspdna conjugate top row a and b red channel, middle row gabapentin dosage nerve pain c and d green channel, bottom row e and f corresponding overlaid images figure shows confocal fluorescence micrographs of cells incubated with mlspdna conjugates, which were vectorized with vesicles made from gabapentin dosage nerve pain the cyclohexyl derivative of dequalinium cdqasomes for the cell exposures gabapentin dosage nerve pain imaged in the left column panels �, � and e gabapentin dosage nerve pain the nonrestricted, ie circular form of pdna was used, while for the experiments pictured in the right column panels b, d and f, the plasmid dna was linearized before dqaplex formation the characteristic red mitochondrial staining pattern panels a and b shows the functional viability of the imaged cells and the intracellular green fluorescence panels � and d demonstrates efficient cell internalization of the fluorescein labeled dna the green and red fluorescence channels gabapentin dosage nerve pain were then overlaid to produce the composite image seen in panels e and f, where the regions of true colocalization gabapentin dosage nerve pain of red and green fluorescence were pseudocolored in white for better gabapentin dosage nerve pain visualization strikingly, in the overlaid images, there is hardly any green fluorescence detectable nearly all areas of green fluorescence in panels � and d appeared as white areas in panels e gabapentin dosage nerve pain and f, strongly suggesting that almost the entire dna has gabapentin dosage nerve pain been delivered not only towards mitochondria, but also into the organelle however, whether all or at least a portion of the pdna has actually entered the mitochondrial matrix, ie has crossed gabapentin dosage nerve pain both mitochondrial membranes, and therefore would potentially be accessible to the mitochondrial transcription machinery, remains yet to be determined dqasomes as carriers of proapoptotic drugs dysregulation of the apoptotic machinery is generally accepted as an almost universal component of the transformation process of normal cells into cancer cells and a large body of experimental data demonstrates that mitochondria play a key role in the complex apoptotic mechanism consequently, any therapeutic strategy aimed at specifically triggering apoptosis in cancer cells is believed to gabapentin dosage nerve pain have potential therapeutic effect, several clinically approved drugs such as vp etoposide, arsenite and vinorelbine, as well as an increasing number of experimental anticancer drugs reviewed by constantini et al, such as betulinic acid, lonidamine, ceramide and cd have been found to act directly on mitochondria, resulting in triggering apoptosis in order to maximize the therapeutic potential of such anticancer drugs, which gabapentin dosage nerve pain are known to act at or inside mitochondria, the use of gabapentin dosage nerve pain dqasomes as a mitochondriaspecific drug delivery system has been proposed hypothetically, dqasomebased anticancer chemotherapy entails features which would make it putatively superior to conventional chemotherapeutic approaches on the cellular, as well as the subcellular level firstly, the delivery of drugs known gabapentin dosage nerve pain to act directly on mitochondria may trigger apoptosis in circumstances gabapentin dosage nerve pain in which conventional drugs fail to act, because endogenous, upstream of gabapentin dosage nerve pain mitochondria apoptosis induction pathways are disrupted secondly, transporting the cytotoxic gabapentin dosage nerve pain drug to its intracellular target could overcome multidrug resistance by hiding the drug inside the delivery system until it becomes selectively gabapentin dosage nerve pain released at the particular intracellular site of action, ie mitochondria gabapentin dosage nerve pain thirdly, many carcinoma cells, including human breast adenocarcinoma derived cells, have an elevated plasma membrane potential relative to their normal gabapentin dosage nerve pain parent cell lines in addition to the higher mitochondrial membrane potential, they could provide the basis for a doubletargeting effect of gabapentin dosage nerve pain dqasomes, ie on the cellular level normal cells vs carcinoma gabapentin dosage nerve pain cells, and on the subcellular level mitochondria versus nucleus first data gabapentin dosage nerve pain involving the encapsulation of anticancer drugs into dqasomes have been published most recently in this study, paclitaxel was chosen as a model compound paclitaxel is known as a potent antitubulin agent used in the treatment of malignancies its therapeutic potential, however, is limited due to a very narrow span between the gabapentin dosage nerve pain maximal tolerated dose and intolerable toxic levels in addition, its poor aqueous solubility requires the formulation of emulsions containing cremophor el�, gabapentin dosage nerve pain an oil of considerable toxicity by itself recently, it has gabapentin dosage nerve pain been demonstrated that clinically relevant concentrations of paclitaxel target mitochondria directly and trigger apoptosis by inducing cytochrome � release in a permeability transition pore ptpdependent manner this mechanism of action is known from the other proapoptotic, directly on mitochondria acting agents a hour delay between the treatment with paclitaxel or with other gabapentin dosage nerve pain ptp inducers, and the release of cytochrome � in cellfree systems, compared with intact cells, has been explained by the existence of several drug targets inside the cell, making only a subset of the drug available for mitochondria consequently, paclitaxel was considered a prime candidate to benefit from a mitochondriaspecific drug delivery gabapentin dosage nerve pain system such as dqasomes it was demonstrated that paclitaxel can be incorporated into dqasomes at a stoichiometric molar ratio of paclitaxel to dequalinium considering the known spherical character of dqasomes, the results of an electron microscopic em analysis of dequasomal incorporated gabapentin dosage nerve pain paclitaxel, however, seem rather surprising the transmission em image fig , gabapentin dosage nerve pain left panel and the cryoem image fig of an identical gabapentin dosage nerve pain sample show a remarkable conformity worm or rodlike structures approximately nm in length, the size of which could also be confirmed by the size distribution analysis shown in fig , right panel the molecular structureof this wormlike complex remains to be determined nevertheless fig left panel transmission electron microscopic image uranyl acetate staining of dqasomal incorporated paclitaxel mol taxolmol dequalinium right panel size distribution analysis of identical preparation shown in left panel the formation gabapentin dosage nerve pain of wormlike micelles as described for selfassembling amphiphilic block copolymers gabapentin dosage nerve pain appears possible � s � i in a preliminary study, paclitaxelloaded dqasomes were tested for their ability to inhibit the growth gabapentin dosage nerve pain of human colon cancer cells in nude mice for controls gabapentin dosage nerve pain with free paclitaxel, the drug was suspended in dmso at mm, stored at �c and immediately diluted in warm medium before gabapentin dosage nerve pain use atenolol and hydroxytryptophan in all controls, the respective dose of free paclitaxel and empty dqasomes was adjusted according to the dose of paclitaxel and dequalinium given in the paclitaxelloaded dqasome sample due to the lack of any inhibitory effect on tumor growth, the gabapentin dosage nerve pain dose was tripled after weeks figure shows that at concentrations where free paclitaxel and r hepes buffer v free paclitaxel empty dqasomes ?