Browsing by Subject "Caco-2 cells"

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  • Bimbo, Luis M.; Sarparanta, Mirkka; Santos, Helder A.; Airaksinen, Anu J.; Makila, Ermei; Laaksonen, Timo; Peltonen, Leena; Lehto, Vesa-Pekka; Hirvonen, Jouni; Salonen, Jarno (AMERICAN CHEMICAL SOCIETY., 2010)
  • Bimbo, Luis M.; Sarparanta, Mirkka; Santos, Helder A.; Airaksinen, Anu J.; Makila, Ermei; Laaksonen, Timo; Peltonen, Leena; Lehto, Vesa-Pekka; Hirvonen, Jouni; Salonen, Jarno (AMERICAN CHEMICAL SOCIETY., 2010)
  • Harloff-Helleberg, Stine; Fliervoet, Lies A. L.; Fano, Mathias; Schmitt, Mechthild; Antopolski, Maxim; Urtti, Arto; Nielsen, Hanne Morck (2019)
    Oral drug delivery is an attractive noninvasive alternative to injectables. However, oral delivery of biopharmaceuticals is highly challenging due to low stability during transit in the gastrointestinal tract (GIT), resulting in low systemic bioavailability. Thus, novel formulation strategies are essential to overcome this challenge. An interesting approach is increasing retention in the GIT by utilizing mucoadhesive biomaterials as excipients. Here, we explored the potential of the GRAS excipient sucrose acetate isobutyrate (SAIB) to obtain mucoadhesion in vivo. Mucoadhesive properties of a 90% SAIB/10% EtOH (w/w) drug delivery system (DDS) were assessed using a biosimilar mucus model and evaluation of rheological behavior after immersion in biosimilar intestinal fluid. To ease readability of this manuscript, we will refer to this as SAIB DDS. The effect of SAIB DDS on cell viability and epithelial membrane integrity was tested in vitro prior to in vivo studies that were conducted using SPECT/CT imaging in rats. When combining SAIB DDS with biosimilar mucus, increased viscosity was observed due to secondary interactions between biosimilar mucus and sucrose ester predicting considerable mucoadhesion. Mucoadhesion was confirmed in vivo, as radiolabeled insulin entrapped in SAIB DDS, remained in the small intestine for up to 22 h after administration. Moreover, the integrity of the system was investigated using the dynamic gastric model under conditions simulating the chemical composition of stomach fluid and physical shear stress in the antrum under fasted conditions. In conclusion, SAIB is an interesting and safe biomaterial to promote high mucoadhesion in the GIT after oral administration.
  • Saarinen, Jukka; Sõzeri, Erkan; Fraser-Miller, Sara; Peltonen, Leena; A. Santos, Helder; Isomäki, Antti; Strachan, Clare J. (2017)
    We have used coherent anti-Stokes Raman scattering (CARS) microscopy as a novel and rapid, label-free and non-destructive imaging method to gain structural insights into live intestinal epithelial cell cultures used for drug permeability testing. Specifically we have imaged live Caco-2 cells in (bio)pharmaceutically relevant conditions grown on membrane inserts. Imaging conditions were optimized, including evaluation of suitable membrane materials and media solutions, as well as tolerable laser powers for non-destructive imaging of the live cells. Lipid structures, in particular lipid droplets, were imaged within the cells on the insert membranes. The size of the individual lipid droplets increased substantially over the 21-day culturing period up to approximately 10% of the volume of the cross section of individual cells. Variation in lipid content has important implications for intestinal drug permeation testing during drug development but has received limited attention to date due to a lack of suitable analytical techniques. CARS microscopy was shown to be well suited for such analysis with the potential for in situ imaging of the same individual cell-cultures that are used for permeation studies. Overall, the method may be used to provide important information about cell monolayer structure to better understand drug permeation results.
  • Donner, Thomas (Helsingin yliopisto, 2020)
    Research into the gut microbiome has increased in recent decades, in part due to advances in sequencing technologies. A number of different disease processes appear to be linked to disturbances in the microbiome and an increase in intestinal permeability. Thus, different methods of modulating the microbiome and intestinal permeability are of great interest when considering future treatment options for several diseases. The experimental part of this thesis examines the effects of a bacterial strain (Bacteroides Vulgatus) on intestinal permeability using a CaCo-2 cell model. The bacterial strain was chosen because previous research has suggested it has the ability to reduce production of interleukin-8 (IL-8). A reduced production of IL-8 is believed to have anti-inflammatory effects and possibly a positive effect on intestinal permeability.The literature review section of the thesis discusses the relationship between disturbances in the microbiome, increased intestinal permeability and inflammatory reactions, as well as possible ways to modulate these processes. Factors that may affect intestinal permeability are briefly discussed with special emphasis placed on dietary factors. Spondyloarthropathies are discussed as an example of a disease group with possible links to a disturbed microbiome and an increase in intestinal permeability. The results from the experimental part of this thesis suggest that the studied strain of B.vulgatus does not have any appreciable effect on intestinal permeability and is thus unlikely to be used for future therapeutic treatments targeting the microbiome.