In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice

We describe a two-photon microscopy-based method to evaluate the in vivo systemic transport of compounds. This method comprises imaging of the intact liver, kidney and intestine, the main organs responsible for uptake and elimination of xenobiotics and endogenous molecules. The image quality of the acquired movies was sufficient to distinguish subcellular structures like organelles and vesicles. Quantification of the movement of fluorescent dextran and fluorescent cholic acid derivatives in different organs and their sub-compartments over time revealed significant dynamic differences. Calculated half-lives were similar in the capillaries of all investigated organs but differed in the specific sub-compartments, such as parenchymal cells and bile canaliculi of the liver, glomeruli, proximal and distal tubules of the kidney and lymph vessels (lacteals) of the small intestine. Moreover, tools to image immune cells, which can influence transport processes in inflamed tissues, are described. This powerful approach provides new possibilities for the analysis of compound transport in multiple organs and can support physiologically based pharmacokinetic modeling, in order to obtain more precise predictions at the whole body scale

Dual delivery of hydrophilic and hydrophobic drugs from chitosan/diatomaceous earth composite membranes

Oral administration of drugs presents important limitations, which are frequently not granted the importance that they really have. For instance, hepatic metabolism means an important drug loss, while some patients have their ability to swell highly compromised (i.e. unconsciousness, cancer...). Sublingual placement of an accurate Pharmaceutical Dosage Form is an attractive alternative. This work explores the use of the beta-chitosan membranes, from marine industry residues, composed with marine sediments for dual sublingual drug delivery. As proof of concept, the membranes were loaded with a hydrophilic (gentamicin) and a hydrophobic (dexamethasone) drug. The physico-chemical and morphological characterization indicated the successful incorporated of diatomaceous earth within the chitosan membranes. Drug delivery studies showed the potential of all formulations for the immediate release of hydrophilic drugs, while diatomaceous earth improved the loading and release of the hydrophobic drug. These results highlight the interest of the herein developed membranes for dual drug delivery.The research leading to these results has received funding from Erasmus Mundus Joint Programmes, ERDF / POCTEP 2007-2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the North Portugal Regional Operational Programme (ON.2 - O Novo Norte), within the National Strategic Reference Framework (QREN 2007-2013) under the project NORTE-01-0124-FEDER-000018. Portuguese Foundation for Science and Technology is also acknowledged for the post-doctoral fellowship SFRH/BPD/112140/2015, for the doctoral fellowship SFRH/BD/112139/2015 and for the funds provided under the program Investigador FCT 2012 (IF/00423/2012). Dr. Helder Santos (University of Helsinki) is also acknowledged for valuable discussions on the concept.The research leading to these results has received funding from Erasmus Mundus Joint Programmes, ERDF / POCTEP 2007–2013 under project 0687_NOVOMAR_1_P, from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement number REGPOT-CT2012-316331-POLARIS, and from the North Portugal Regional Operational Programme (ON.2 – O Novo Norte), within the National Strategic Reference Framework (QREN 2007-2013) under the project NORTE-01-0124-FEDER-000018. Portuguese Foundation for Science and Technology is also acknowledged for the post-doctoral fellowship SFRH/BPD/112140/2015, for the doctoral fellowship SFRH/BD/112139/2015 and for the funds provided under the program Investigador FCT 2012 (IF/00423/2012). Dr. Hélder Santos (University of Helsinki) is also acknowledged for valuable discussions on the concept.info:eu-repo/semantics/publishedVersio