New heat pads: dynamic PK data from dry powders, with XposeALI
XposeALI now simulates lung conditions more closely. New heat pads keep the system’s pumped perfusate at body temperature, 370 C. As a result XposeALI now provides PK (pharmacokinetic) data and a PK prolife of the behaviors of substances in the lung over time: A valuable benefit for drug development as well as environmental research.
XposeALI delivers dynamic data from dry powder aerosols. It is already valued by environmental researchers for its ability to expose cells cultured at an Air / Liquid Interface (ALI) to fine, evenly dispersed aerosols. This makes it possible to, for example, study the effects of airborne nanoparticle pollutants, and monitor how they affect the cellular viability and inflammatory response.
But now new features, including pumped perfusate and heated pads, keep the module’s perfusate at body temperature, letting XposeALI generate PK data over time and plot a PK profile, including cmax and tmax, – a significant advantage for inhaled drug developers.
How do the perfusate heating pads work?
Maria Malmlöf, ISAB’s in vitro studies manager: “The perfusate is heated to 370 inside the pad, and pumped just below the Transwell membrane that the cells are cultivated on. As in the real lung, cells are exposed to aerosols from above. We measure how particles dissolve in the lungs over time by collecting fractions of the perfusate at intervals over time. After the sample analysis a PK profile with cmax and tmax characteristics can be plotted.”
Moving closer to IVIVC with dynamic perfusion
IVIVC (in vivo in vitro correlation) is becoming ever more strategically important for inhalation researchers. Regulators in Europe, for example, recently accepted in vitro findings in early stage inhaler trials. Being able to get in vitro data that reliably predicts in vivo data early on can save a lot of money – preventing costly reformulation of test substances and even clinical failure during drug development.
However, most aerosol and cell R&D technologies are essentially static perfusion systems, gathering samples in the media underneath the exposed cell layer. Static perfusion can often underestimate absorption rates of inhalants because of saturation, producing non-in-vivo-like absorption curves. XposeALI has both dynamic and static diffusion modes, enabling in-vivo-like data, cross validation with ex vivo / in vivo models and avoiding the risk of saturating the receiving medium.
“We want both our in vitro lung simulation module, DissolvIt, and our cell culturing module XposeALI, to be used side-by-side and complement each other,” says Malmlöf. “XposeALI is excellent at understanding the effects of airborne particles inhaled in the lung over time.”