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Residual antibiotics reaching the colon have many deleterious effects on the colonic microbiota including the selection of new antibiotic resistances. In order to avoid the selection of ciprofloxacin resistance, intestine or colon-targeted zinc-pectinate beads containing activated charcoal (AC) were designed for the inactivation of residual ciprofloxacin in the gastrointestinal tract of rats. Bead stability after oral administration was adjusted by tuning the concentration of zinc in the gelling bath and the number of washings. Intestine and colon-targeted beads were administered along with 50mg/kg of ciprofloxacin and ciprofloxacin was dosed in the plasma and the feces using HPLC. Ciprofloxacin pharmacokinetics was not affected by the oral co-administration of beads. The co-administration of intestine-targeted beads led to a significant decrease of the residual fecal free ciprofloxacin with a pronounced dose effect. Our study suggests the rat model is not appropriate for the investigation of bacteria responsive colon-targeted beads probably due to the important anatomical and physiological differences between human and rat gastrointestinal tracts. The ability of AC loaded zinc-pectinate beads to selectively decrease the intestinal residual fraction of ciprofloxacin could provide a better protection of the intestinal microbiota and may prevent the emergence of ciprofloxacin resistance in the gastrointestinal tract.

The surface of polymeric nanocapsules used as ultrasound contrast agents (UCAs) was modified with PEGylated phospholipids in order to escape recognition and clearance by the mononuclear phagocyte system and achieve passive tumor targeting. Nanocapsules consisted of a shell of poly(lactide-co-glycolide) (PLGA) encapsulating a liquid core of perfluorooctyl bromide (PFOB). They were decorated with poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) incorporated in the organic phase before the solvent emulsification-evaporation process. The influence of DSPE-PEG concentration on nanocapsule size, surface charge, morphology, hydrophobicity and complement activation was evaluated. Zeta potential measurements, Hydrophobic interaction chromatography and complement activation provide evidence of DSPE-PEG presence at nanocapsule surface. Electronic microscopy reveals that the core/shell structure is preserved up to 2.64 mg of DSPE-PEG for 100 mg PLGA. In vivo ultrasound imaging was performed in mice bearing xenograft tumor with MIA PaCa-2 cells, either after an intra-tumoral or intravenous injection of nanocapsules. Tumor was observed only after the intra-tumoral injection. Despite the absence of echogenic signal in the tumor after intravenous injection of nanocapsules, histological analysis reveals their accumulation within the tumor tissue demonstrating that tissue distribution is not the unique property required for ultrasound contrast agents to be efficient.