TY - JOUR
T1 - Co-existing colloidal phases of human duodenal aspirates
T2 - Intraindividual fluctuations and interindividual variability in relation to molecular composition
AU - Elvang, Philipp A
AU - Bohsen, Mette Sloth
AU - Stein, Paul C
AU - Bauer-Brandl, Annette
AU - Riethorst, Danny
AU - Brouwers, Joachim
AU - Augustijns, Patrick
AU - Brandl, Martin
N1 - Copyright © 2019 Elsevier B.V. All rights reserved.
PY - 2019/6/5
Y1 - 2019/6/5
N2 - We investigated the ultrastructural pattern of colloidal phases in human duodenal fluids. Aspirates were collected from three volunteers in both fasted and fed nutritional states. Analysis methods comprised the combination of asymmetric flow field-flow fractionation (AF4) and multi-angle laser light scattering (MALLS). Furthermore, dynamic light scattering (DLS) and diffusion-ordered NMR spectroscopy (DOSY-NMR) were employed as alternative analytical approaches for comparison. By AF4/MALLS, up to four, and in some cases up to five distinct co-existing fractions could be differentiated in the sub-micron size-range, which, in accordance with a previous study (Elvang et al., 2018), may be assigned to three main types, namely small bile salt micelles, intermediate size mixed bile salt/phospholipid micelles and large phospholipid aggregates / vesicles. Although more or less the same colloidal phases were found to co-exist in all aspirates, their prevalence was found to vary, both over time and between the three individual human volunteers. Any uniform changes of patterns of colloidal phases over time, however, could not be identified. On the other hand, prevalence of specific colloidal phases was identified for aspirates of individual volunteers, which correlated reasonably well with the prevalence of certain lipid species in their molecular composition. It remains to be investigated whether such prevalence of specific colloidal phases influences drug solubilizing capacity as well as drug absorption. If so, this may help to better understand the substantial inter-individual variability seen in many drug absorption profiles.
AB - We investigated the ultrastructural pattern of colloidal phases in human duodenal fluids. Aspirates were collected from three volunteers in both fasted and fed nutritional states. Analysis methods comprised the combination of asymmetric flow field-flow fractionation (AF4) and multi-angle laser light scattering (MALLS). Furthermore, dynamic light scattering (DLS) and diffusion-ordered NMR spectroscopy (DOSY-NMR) were employed as alternative analytical approaches for comparison. By AF4/MALLS, up to four, and in some cases up to five distinct co-existing fractions could be differentiated in the sub-micron size-range, which, in accordance with a previous study (Elvang et al., 2018), may be assigned to three main types, namely small bile salt micelles, intermediate size mixed bile salt/phospholipid micelles and large phospholipid aggregates / vesicles. Although more or less the same colloidal phases were found to co-exist in all aspirates, their prevalence was found to vary, both over time and between the three individual human volunteers. Any uniform changes of patterns of colloidal phases over time, however, could not be identified. On the other hand, prevalence of specific colloidal phases was identified for aspirates of individual volunteers, which correlated reasonably well with the prevalence of certain lipid species in their molecular composition. It remains to be investigated whether such prevalence of specific colloidal phases influences drug solubilizing capacity as well as drug absorption. If so, this may help to better understand the substantial inter-individual variability seen in many drug absorption profiles.
KW - Bile salts
KW - Colloids
KW - Field-flow fractionation
KW - Gastrointestinal
KW - Human bile
KW - Light scattering
KW - Micelles
U2 - 10.1016/j.jpba.2019.03.026
DO - 10.1016/j.jpba.2019.03.026
M3 - Journal article
C2 - 30903926
VL - 170
SP - 22
EP - 29
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
IS - June
ER -