Insights into intermediate phases of human intestinal fluids visualized by atomic force microscopy and cryo-transmission electron microscopy ex vivo

TY - JOUR

T1 - Insights into intermediate phases of human intestinal fluids visualized by atomic force microscopy and cryo-transmission electron microscopy ex vivo

AU - Müllertz, Anette

AU - Fatouros, Dimitrios G.

AU - Smith, James R.

AU - Vertzoni, Maria

AU - Reppas, Christos

PY - 2012/2/6

Y1 - 2012/2/6

N2 - The current work aims to study at the ultrastructural level the morphological development of colloidal intermediate phases of human intestinal fluids (HIFs) produced during lipid digestion. HIFs were aspirated near the ligament of Treitz early (30 min), Aspirate early, and 1 h, Aspirate 1h ave,comp, after the administration of a heterogeneous liquid meal into the antrum. The composition of the sample aspirated 1 h after meal administration was similar to the average lumenal composition 1 h after meal administration (Aspirate 1h ave,comp). The colloidal structures of individual aspirates and supernatants of aspirates after ultracentrifugation (micellar phase) were characterized by means of atomic force microscopy (AFM) and cryogenic transmission electron microscopy (Cryo-TEM). AFM revealed domain-like structures in Aspirate early and both vesicles and large aggregates Aspirate 1h ave,comp. Rough surfaces and domains varying in size were frequently present in the micellar phase of both Aspirate early and Aspirate 1h ave,comp. Cryo-TEM revealed an abundance of spherical micelles and occasionally presented worm-like micelles coexisting with faceted and less defined vesicles in Aspirate early and Aspirate 1h ave,comp. In Aspirate 1h ave,comp oil droplets were visualized with bilayers closely located to their surface suggesting lipolytic product phases accumulated on the surface of the oil droplet. In the micellar phase of Aspirate 1h ave,comp, Cryo-TEM revealed the presence of spherical micelles, small vesicles, membrane fragments, oil droplets and plate-like structures. In the micellar phase of Aspirate 1h ave,comp, the only difference was the absence of oil droplets. Visualization studies previously performed with biorelevant media revealed structural features with many similarities as presented in the current investigation. The impression of the complexity and diversion of these phases has been reinforced with the excessive variation of structural features visualized ex vivo in the current study offering insights at the ultrastuctural level of intermediate phases which impact drug solubilization.

AB - The current work aims to study at the ultrastructural level the morphological development of colloidal intermediate phases of human intestinal fluids (HIFs) produced during lipid digestion. HIFs were aspirated near the ligament of Treitz early (30 min), Aspirate early, and 1 h, Aspirate 1h ave,comp, after the administration of a heterogeneous liquid meal into the antrum. The composition of the sample aspirated 1 h after meal administration was similar to the average lumenal composition 1 h after meal administration (Aspirate 1h ave,comp). The colloidal structures of individual aspirates and supernatants of aspirates after ultracentrifugation (micellar phase) were characterized by means of atomic force microscopy (AFM) and cryogenic transmission electron microscopy (Cryo-TEM). AFM revealed domain-like structures in Aspirate early and both vesicles and large aggregates Aspirate 1h ave,comp. Rough surfaces and domains varying in size were frequently present in the micellar phase of both Aspirate early and Aspirate 1h ave,comp. Cryo-TEM revealed an abundance of spherical micelles and occasionally presented worm-like micelles coexisting with faceted and less defined vesicles in Aspirate early and Aspirate 1h ave,comp. In Aspirate 1h ave,comp oil droplets were visualized with bilayers closely located to their surface suggesting lipolytic product phases accumulated on the surface of the oil droplet. In the micellar phase of Aspirate 1h ave,comp, Cryo-TEM revealed the presence of spherical micelles, small vesicles, membrane fragments, oil droplets and plate-like structures. In the micellar phase of Aspirate 1h ave,comp, the only difference was the absence of oil droplets. Visualization studies previously performed with biorelevant media revealed structural features with many similarities as presented in the current investigation. The impression of the complexity and diversion of these phases has been reinforced with the excessive variation of structural features visualized ex vivo in the current study offering insights at the ultrastuctural level of intermediate phases which impact drug solubilization.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/mp200286x

DO - 10.1021/mp200286x

M3 - Journal article

C2 - 22136289

SN - 1543-8384

VL - 9

SP - 237

EP - 247

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 2

ER -