PEGDA hydrogels as a replacement for animal tissues in mucoadhesion testing.

Utilization of animal parts in ex-vivo mucoadhesion assays is a common approach that presents many difficulties due to animal rights issues and large variance between animals. This study examines the suitability of two PEGDA (poly(ethylene glycol) diacrylate) based hydrogels to serve as tissue mimetics for mucoadhesion evaluation. One hydrogel, termed PEGDA-QT, was composed of pentaerythritol tetrakis (3-mercaptopropionate) and PEG and contained free thiol groups mimicking those found in natural mucosa. The other hydrogel was formed by UV (ultraviolet) curing of PEGDA and mimicked the mechanical property of mucosa but not its chemical constitute. When ranking different first generation mucoadhesive polymers using a tensile assay, both hydrogels showed good agreement with the ranking achieved for porcine small intestine. However, only PEGDA-QT and porcine small intestine shared a similar displacement curve. The same ranking for PEGDA-QT and porcine small intestine was also observed when comparing a second-generation mucoadhesive polymer, thiolated alginate, to native alginate. Our findings suggest that PEGDA-QT could serve as a replacement for porcine small intestine in both mucoadhesion evaluations using a tensile machine and the flow-through method for first and second-generation mucoadhesive polymers.

Mucoadhesive acrylated block copolymers micelles for the delivery of hydrophobic drugs.

Blockpolymer micelles having acrylated end groups were fabricated for the development of mucoadhesive drug loaded vehicle. The critical micelle concentration (CMC) of Pluronic(®) F127 modified with acrylate end groups (F127DA) was found to be similar to that of the unmodified Pluronic(®) F127 (F127). Small angle X-ray scattering verified existence of micelles with an inner core of 4.9±0.2 and 5.5±0.3 for F127 and F127DA respectively. Indomethacin, a hydrophobic drug, was incorporated into the micelles using the thin-film hydration method. In vitro drug release assay demonstrated that the micelles sustained the release of the drug in comparison with free drug in solution. Several methods were used for mucoadhesion evaluation. Viscosity profiling was performed by shear rate sweep experiment of hydrated commercial mucin, F127 or F127DA, and combination of both mucin and a copolymer. Elevated viscosity was achieved for acrylated micelles with mucin compared to mixtures of non-acrylated micelles with mucin. The mucoadhesivity of the acrylated micelles was further characterized using nuclear magnetic resonance (NMR); data affirmed the Michael type addition reaction occurred between acrylates on the micelles corona and thiols present in the mucin. SAXS scattering data further showed a modification in the scattering of F127DA micelles with the addition of pig gastric mucin. Cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) data detected increase in the aggregates size while using acrylated micelles enhance mucoadhesion. Thus acrylated F127DA micelles were found to be mucoadhesive, and a suitable and preferred candidate for micellar drug delivery to mucosal surfaces.

Effect of sex difference on platelet adhesion, spreading and aggregate formation under flow.

There are clear but poorly understood differences in the etiology and prognosis of thrombotic diseases in men and women. Due to the fact that platelets play a central role in the formation of occlusive thrombi in atherosclerotic coronary arteries, previous studies have examined whether sex differences exist for platelets, and have obtained conflicting results. Additionally, due to the increased use of genetically modified mouse models to explore the molecular mechanisms underlying platelet activation and thrombotic disorders, it is critical to determine if sex is a confounding variable. Our study of the role of sex differences in platelet function was designed to utilise purified platelets from inbred paired female/male littermates in order to minimise genetic and environmental variability. In the current study, we demonstrate that platelet adhesion to and spreading on immobilised fibrinogen, thrombin or collagen was equivalent for both female and male mouse platelets. The ability of the soluble agonist thrombin or convulxin to potentiate platelet P-selectin exposure, fibrinogen binding, or adhesion and spreading on immobilised fibrinogen was equivalent for both female and male mouse platelets. Our data show that an equivalent degree of platelet adhesion and aggregation on collagen or fibrinogen under shear flow was observed for both female and male mouse platelets. In conclusion, our data would argue against an intrinsic difference for female mouse platelets in regulating the major functional platelet responses: platelet adhesion, spreading, or aggregation under flow.