Characterization of the epithelial permeation enhancing effect of basic butylated methacrylate copolymer--in vitro studies. 2008

Stefan Grube, and Uwe Wolfrum, and Peter Langguth
Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University, Saudinger Weg 5, Mainz, Germany.

Membrane destabilizing properties and increased efflux of doxorubicin from liposomes caused by basic butylated methacrylate copolymer (BBMC), better known under its commercial trade name EUDRAGIT E, have been described in the scientific literature. Here, we investigated the effect of BBMC on suspended and filter-grown Caco2 cells with respect to apical-to-basal transport and membrane permeabilization using transport assays, trypan blue exclusion assay, measurements of transepithelial electrical resistance (TEER), confocal laser scanning microscopy, and transmission electron microscopy. The effect of inhibiting protein phosphatase 2A (PP2A) by okadaic acid was investigated by measuring TEER, but a link between PP2A and the observed effects could not be established. Overall, membrane permeabilization of Caco2 cells by BBMC was demonstrated, which went along with increased apical-to-basal transport of the model compounds mannitol, talinolol, and trospium. The effect was concentration- and time-dependent, and reversible. Enhancement occurred at polymer concentrations as low as 20 microg/mL.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008689 Methacrylates Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group. Methacrylate
D008768 Methylmethacrylates The methyl esters of methacrylic acid that polymerize easily and are used as tissue cements, dental materials, and absorbent for biological substances.
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D016764 Cell Polarity Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. Cell Polarities,Polarities, Cell,Polarity, Cell
D054648 Protein Phosphatase 2 A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes. PPP2CA Phosphatase,PPP2CB Phosphatase,Protein Phosphatase 2, Catalytic Subunit,Protein Phosphatase 2, Catalytic Subunit, alpha Isoform,Protein Phosphatase 2, Catalytic Subunit, beta Isoform,Protein Phosphatase 2, Regulatory Subunit,Protein Phosphatase 2, Regulatory Subunit A, alpha Isoform,Protein Phosphatase 2, Regulatory Subunit A, beta Isoform,Protein Phosphatase 2, Regulatory Subunit B, alpha Isoform,Protein Phosphatase 2, Regulatory Subunit B, beta Isoform,Protein Phosphatase 2, Regulatory Subunit B, delta Isoform,Protein Phosphatase 2, Regulatory Subunit B, gamma Isoform,Protein Phosphatase 2A, Catalytic Subunit, alpha Isoform,Protein Phosphatase 2A, Catalytic Subunit, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit A , alpha Isoform,Protein Phosphatase 2A, Regulatory Subunit A, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, alpha Isoform,Protein Phosphatase 2A, Regulatory Subunit B, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, delta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, gamma Isoform,Protein Phosphatase-2A,Serine Threonine Protein Phosphatase 2A Catalytic Subunit beta Isoform,Serine-Threonine-Protein Phosphatase 2A Catalytic Subunit alpha Isoform,Phosphatase, PPP2CA,Phosphatase, PPP2CB,Protein Phosphatase 2A,Serine Threonine Protein Phosphatase 2A Catalytic Subunit alpha Isoform

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