ganglioside--gd2 and sepantronium

Sepantronium bromide (YM155) is a hydrophilic quaternary compound that cannot be administered orally due to its low oral bioavailability; it is furthermore rapidly eliminated via the kidneys. The current study aims at improving the pharmacokinetic profile of YM155 by its formulation in immunoliposomes that can achieve its enhanced delivery into tumor tissue and facilitate uptake in neuroblastoma cancer cells.. PEGylated YM155 loaded liposomes composed of DPPC, cholesterol and DSPE-PEG. YM155 loaded immunoliposomes had a size of 170 nm and zeta potential of -10 mV, with an antibody coupling efficiency of 60% andYM155 encapsulation efficiency of14%. Targeted and control liposomal formulations were found to have similar YM155 release rates in a release medium containing 50% serum. An in-vitro toxicity study on KCNR cells showed less toxicity for immunoliposomes as compared to free YM155. In-vivo pharmacokinetic evaluation of YM155 liposomes showed prolonged blood circulation and significantly increased half-lives of liposomal YM155 in tumor tissue, as compared to a bolus injection of free YM155.. YM155 loaded immunoliposomes were successfully formulated and characterized, and initial in-vivo results show their potential for improving the circulation time and tumor accumulation of YM155.

Topics: Animals; Antibodies; Antineoplastic Agents; Cell Line, Tumor; Drug Compounding; Drug Liberation; Drug Stability; Female; Gangliosides; Half-Life; Humans; Hydrophobic and Hydrophilic Interactions; Imidazoles; Injections, Intravenous; Liposomes; Mice; Mice, Nude; Naphthoquinones; Neuroblastoma; Pilot Projects; Polyethylene Glycols; Survivin; Xenograft Model Antitumor Assays