PLGA-PEG-Mal from PolySciTech used in investigating hypergravity effects on intestinal permeability during space travel.

 

Various physiological conditions are affected by surrounding environment. In general, on Earth, the gravitational force is constant (1G) in the absence of rapid acceleration or spinning motion. Within the context of an eventual time when space-travel becomes common-place enough for such parameters as gravitational force to matter, there should be at least some understanding around intestinal uptake under this condition. Recently, researchers at Universidade do Porto (Portugal), European Space Agency, Amsterdam University Medical Center (Netherlands), and CESPU (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create particles decorated with Fc receptors to investigate intestinal uptake under varying gravitational forces. Having some understanding around this process will become relevant in the future with increased space travel. Read more: Azevedo, Cláudia, Maria Helena Macedo, Andreia Almeida, Soraia Pinto, Jack JWA van Loon, and Bruno Sarmento. "The effect of hypergravity in intestinal permeability of nanoformulations and molecules." European Journal of Pharmaceutics and Biopharmaceutics (2021). https://www.sciencedirect.com/science/article/pii/S0939641121000801

“Highlights: First study describing the impact of hypergravity on intestinal absorption. Metabolic activity and integrity of intestinal cells are not influenced by hypergravity. Hypergravity can affect the expression of different proteins on intestinal cells. The effect of hypergravity on intestinal absorption is dependent of the molecule and absorption mechanism. Abstract: The oral administration of drugs remains a challenge due to rapid enzymatic degradation and minimal absorption in the gastrointestinal tract. Mechanical forces, namely hypergravity, can interfere with cellular integrity and drug absorption, and there is no study describing its influence in the intestinal permeability. In this work, it was studied the effect of hypergravity on intestinal Caco-2 cells and its influence in the intestinal permeability of different nanoformulations and molecules. It was shown that the cellular metabolic activity and integrity were maintained after exposure to different gravity-levels (g-levels). Expression of important drug transporters and tight junctions’ proteins was evaluated and, most proteins demonstrated a switch of behavior in their expression. Furthermore, paracellular transport of FITC-Dextran showed to significantly increase with hypergravity, which agrees with the decrease of transepithelial electrical resistance and the increase of claudin-2 at higher g-levels. The diffusion of camptothecin released from polymeric micelles revealed a significant decrease, which agrees with the increased expression of the P-gp observed with the increase in g-levels, responsible for pumping this drug out. The neonatal Fc receptor-mediated transport of albumin-functionalized nanoparticles loaded with insulin showed no significant changes when increasing the g-levels. Thus, this study supports the effect of hypergravity on intestinal permeability is dependent on the molecule studied and the mechanism by which it is absorbed in the intestine.”