Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures.

Purpose CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15. Methods Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2–10. Results This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a ‘classical’ tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton. Conclusion Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening

Search for invisible modes of nucleon decay in water with the SNO+ detector

This paper reports results from a search for nucleon decay through invisible modes, where no visible energy is directly deposited during the decay itself, during the initial water phase of SNO+. However, such decays within the oxygen nucleus would produce an excited daughter that would subsequently deexcite, often emitting detectable gamma rays. A search for such gamma rays yields limits of 2.5×1029  y at 90% Bayesian credibility level (with a prior uniform in rate) for the partial lifetime of the neutron, and 3.6×1029  y for the partial lifetime of the proton, the latter a 70% improvement on the previous limit from SNO. We also present partial lifetime limits for invisible dinucleon modes of 1.3×1028  y for nn, 2.6×1028  y for pn and 4.7×1028  y for pp, an improvement over existing limits by close to 3 orders of magnitude for the latter two