Ascorbyl palmitate/DSPE-PEG nanocarriers for oral iron delivery: Preparation, characterisation and in vitro evaluation

The objective of this study was to encapsulate iron in nanocarriers formulated with ascorbyl palmitate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol (DSPE-PEG) for oral delivery. Blank and iron (Fe) loaded nanocarriers were prepared by a modified thin film method using ascorbyl palmitate and DSPE-PEG. Surface charge of the nanocarriers was modified by the inclusion of chitosan (CHI) during the formulation process. Blank and iron loaded ascorbyl palmitate/DSPE nanocarriers were visualised by transmission electron microscopy (TEM) and physiochemical characterisations of the nanocarriers carried out to determine the mean particle size and zeta potential. Inclusion of chitosan imparted a net positive charge on the nanocarrier surface and also led to an increase in mean particle size. Iron entrapment in ascorbyl palmitate-Fe and ascorbyl palmitate-CHI-Fe nanocarriers was 67% and 76% respectively, suggesting a beneficial effect of chitosan on nanocarrier Fe entrapment. Iron absorption was estimated by measuring Caco-2 cell ferritin formation using ferrous sulphate as a reference standard. Iron absorption from ascorbyl palmitate-Fe (592.17 ± 21.12 ng/mg cell protein) and ascorbyl palmitate-CHI-Fe (800.12 ± 47.6 ng/mg, cell protein) nanocarriers was 1.35-fold and 1.5-fold higher than that from free ferrous sulphate, respectively (505.74 ± 23.73 ng/mg cell protein) (n = 6, p < 0.05). This study demonstrates for the first time preparation and characterisation of iron loaded ascorbyl palmitate/DSPE PEG nanocarriers, and that engineering of the nanocarriers with chitosan leads to a significant augmentation of iron absorption

Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea-predominant irritable bowel syndrome measured using serial MRI

Background Previous assessments of colon morphology have relied on tests which were either invasive or used ionizing radiation. We aimed to measure regional volumes of the undisturbed colon in healthy volunteers (HV) and patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Methods 3D regional (ascending, transverse, and descending) colon volumes were measured in fasting abdominal magnetic resonance (MR) images of 75 HVs and 25 IBS-D patients. Thirty-five of the HV and all 25 IBS-D subjects were fed a standard meal and postprandial MRI data obtained over 225 min. Key Results Colonic regions were identified and 3D maps from cecum to sigmoid flexure were defined. Fasted regional volumes showed wide variation in both HVs being (mean ± SD) ascending colon (AC) 203 ± 75 mL, transverse (TC) 198 ± 79 mL, and descending (DC) 160 ± 86 mL with no difference from IBS-D subjects (AC 205 ± 69 mL, TC 232 ± 100 mL, and DC 151 ± 71 mL, respectively). The AC volume expanded by 10% after feeding (p = 0.007) in the 35 HV possibly due to increased ileo-colonic inflow. A later rise in AC volume occurred from t = 90 to t = 240 min as the meal residue entered the cecum. In contrast, IBS-D subjects showed a much reduced postprandial response of the AC (p < 0.0001) and a greater increase in TC volume after 90 min (p = 0.0244) compared to HV. Conclusions & Inferences We have defined a normal range of the regional volumes of the undisturbed colon in fasted and fed states. The AC in IBS-D appeared less able to accommodate postprandial inflow which may account for faster colonic transit

Cholesterol-bile salt vesicles as potential delivery vehicles for drug and vaccine delivery.

The aim of this study was to further investigate the interactions between cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium deoxycholate) and their suitability for drug and vaccine delivery. Insulin was used as a model protein to assess the ability of CH:BS vesicles to entrap a therapeutically relevant macromolecule. The association of protein (FITC-insulin) with the CH:BS structure was confirmed with fluorescence microscopy, and the overall morphology of the vesicles was examined with atomic force microscopy (AFM). Results demonstrate that the nature of the vesicles formed between CH and BS is dependent not only on the concentration of BS but also on the increasing CH concentration leading to CH crystal formation

Electroformation of Giant Vesicles from an Inverse Phase Precursor

We discuss a simple modification of the well-known method of giant vesicle electroformation that allows for a direct addition of water-soluble species to the phospholipid bilayers. Using this modified method, we prepare phospholipid vesicles decorated with chitosan, a water-soluble polysaccharide currently investigated for potential pharmacological applications. We find that the method allows this polysaccharide with primary amino groups on every glucose subunit to be tightly bound to the membrane, rather than simply being encapsulated

Effect of experimental stress on the small bowel and colon in healthy humans

BACKGROUND: Symptoms of irritable bowel syndrome (IBS) are frequently reported to be exacerbated by stress. Animal studies suggest that corticotrophin releasing hormone (CRH) mediates the effect of stress on the bowel. We have shown that stressed IBS patients with diarrhea have constricted small bowels. We hypothesized that we could mimic this effect by applying experimental stress in the form of either hand immersion in ice water or CRH injection in healthy volunteers (HV). METHODS: The postprandial effect of the cold pressor test (repeated hand immersion in ice cold water) and injection of CRH, were assessed vs control in two groups of 18 HVs. KEY RESULTS: CRH produced a significant rise from baseline salivary cortisol levels (p = 0.004) not seen with the cold pressor test. Small bowel water content (SBWC) fell postprandially on all four treatments. SBWC was significantly reduced by both stressors but CRH caused a greater effect (anova, p < 0.003 vs p = 0.02). Ascending colon (AC) volume was greater after CRH injection compared with saline (p = 0.002) but no differences were seen with the cold pressor test vs warm water. Postprandial increase in colon volume was also reduced by CRH which also increased the sensations of distension and bloating. CONCLUSIONS & INFERENCES: Two experimental stressors were shown to constrict the small bowel, mimicking the effect previously seen in IBS-D patients. CRH increased the volume of the AC. We speculate that stress accelerates transfer of water from the small bowel to the AC