Learn More
A two-chamber culture system has been used to examine the ability of small liposomes to cross an endothelial cell barrier in response to various stimuli. Transendothelial transit of liposomes was almost negligible in the presence of intact, healthy endothelial cells (EC). Addition of histamine induced a concentration-dependent increase in the movement of(More)
The development of long-circulating formulations of liposomes (S-liposomes), sterically stabilized with lipid derivatives of poly(ethylene glycol) (PEG), has increased the likelihood that these liposomes, coupled to targeting ligands such as antibodies, could be used as drug carriers to deliver therapeutic drugs to specific target cell populations in vivo.(More)
Several coupling methods for binding antibodies (Ab) to liposomes have previously been developed. We were interested in examining if some of these methods would be suitable for attaching Ab to long-circulating formulations of liposomes (SL), sterically stabilized with poly(ethylene glycol) (PEG). We studied three 'classical' coupling methods in which Ab was(More)
Cationic liposomes are considered to be safe vectors for gene transfer, but they are less efficient at delivering DNA to cells when compared with retroviral vectors. Cationic liposomes complexed with DNA were targeted to specific cells in vitro by means of monoclonal antibodies (mAbs) or ligands associated with the liposomes. Significant increases in(More)
The goal of this study was to develop a small, stable liposomal carrier for antisense oligodeoxynucleotides (asODN) that would have high trapping efficiencies and long circulation times in vivo. Traditional cationic liposomes aggregate to large complexes and, when injected intravenously, rapidly accumulate in the liver and lung. We produced(More)
A number of Mannich bases of alicyclic ketones containing one and two basic centres were prepared in order to evaluate the theory of sequential cytotoxicity and develop structure-activity relationships in these series of compounds. The compounds were evaluated in vitro against murine P388 D1 lymphocytic leukemia cells. The data generated supported the(More)
A number of 1-aryl-1-penten-3-ones 1 and related Mannich bases 2 were synthesized and converted either directly or indirectly to the corresponding biscarbohydrazones 3 and 4. Reaction of representative unsaturated ketones with thiocarbohydrazide led to the formation of only the monothiocarbohydrazones 5. The cytotoxicity of these compounds against murine(More)
Dopamine sulfate (DAS) is formed by the action of phenolsulfotransferase (PST) on dopamine (DA). Since probenecid is often used to investigate the transport of monoamine acidic metabolites such as DAS from the brain, we investigated the effect of probenecid on rat brain PST activity utilizing DA as substrate. In the presence of 30 or 90 microM DA,(More)
Reaction of 1-(4-bromophenyl)-4,4-dimethyl-5-(1-piperidino)-1-penten-3-one hydrochloride (1f) with sodium 2-mercaptoethanesulphonate (mesna) gave rise to the thiol adduct. 3. Recrystallization of this compound led to the formation of the corresponding zwitterion 4f. A series of analogues of 4f were prepared and the structure of a representative compound was(More)
The syntheses of a series of 1-aryl-5-diethylamino-1-penten-3-one hydrochlorides 1 and 1-aryl-3-diethylamino-1-propanone hydrochlorides 4 were accomplished. Attempts to prepare the corresponding bis(5-aryl-3-oxo-4-pentenyl)ethylamine hydrochlorides 2 and bis(3-aryl-3-oxopropyl)ethylamine hydrochlorides 5 led to the formation of a series of(More)