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Rae Record

Publications and source records attributed to Rae Record.

4 recordsLinked to original sources

Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins.

The challenges faced to orally deliver therapeutic agents with unfavorable physicochemical properties, such as proteins, have been the primary motivation for the design and development of novel oral delivery systems that could circumvent biological barriers. In this work, we examined complexation-sensitive hydrogel nanospheres composed of poly[methacrylic acid-grafted-poly(ethylene glycol)] (P(MAA-g-EG)), on a model biological environment. For this purpose, a gastrointestinal cell culture model, the Caco-2 cell line, was employed to investigate the cytotoxic effects of the polymeric carrier and its effects on the cell monolayer integrity. The determination of the cytotoxic effects of the polymer network on the cell monolayer was performed by a colorimetric assay and by the counting of viable cells using the trypan blue exclusion method. Electrophysiological measurements were performed to measure the transepithelial electrical resistance changes in the monolayers in the presence and absence of the nanosphere suspension. The examination of the physicochemical interactions of the P(MAA-g-EG) nanosphere system with Caco-2 cell monolayers revealed that these systems possessed low cytotoxicity and were capable of opening the tight junctions between epithelial cells, therefore significantly reducing the transepithelial electrical resistance.

Administration, Oral↗

Fibronectin peptides mediate HMEC adhesion to porcine-derived extracellular matrix.

Extracellular matrices (ECM) derived from porcine tissues have been shown to support the successful repair and remodeling of injured tissues when evaluated in animal models. Cell-matrix interactions, including ligand-integrin associations that facilitate endothelial cell adhesion, are clearly important in the tissue remodeling process. The goal of the present study was to identify the peptide sequences within the ubiquitous protein fibronectin (FN) that may be important in the initial interactions between the host endothelial cells and the ECM scaffold. Human microvascular endothelial cells (HMEC) were seeded upon porcine ECM after having been subjected to pretreatment with peptide ligands derived from tissue FN and were allowed to attach for 20 min. Non-adherent cells were removed and the remaining, tritium-labeled cells attached to the ECM were counted. Results showed that cyclo-RGD and REDV, but not LDV or PHSRN, play a role in mediating the attachment of HMEC to porcine ECM.

Animals↗

Antimicrobial activity associated with extracellular matrices.

Materials derived from extracellular matrices (ECMs) are being evaluated as scaffolds for surgical reconstruction of damaged or missing tissues. It is important to understand the susceptibility of these biological materials to bacterial infections. ECMs derived from porcine small intestinal submucosa (SIS) and urinary bladder submucosa (UBS) were found to possess antimicrobial activity. ECM extracts, obtained by digesting these acellular matrices in acetic acid, demonstrated antibacterial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Antimicrobial activity was determined using a minimal inhibitory concentration assay. Bacteriostatic activity was detected at protein concentrations of ECM extracts equivalent to 0.77-1.60 mg/mL. ECM extracts were found to inhibit bacterial growth for up to at least 13 h. The resulting extracts consisted of water-soluble peptides and proteins with molecular weights ranging from <4 to >100 kDa and lower molecular weight compounds, as determined by size exclusion liquid chromatography.

Animals↗

pH-Sensitive hydrogels as gastrointestinal tract absorption enhancers: transport mechanisms of salmon calcitonin and other model molecules using the Caco-2 cell model.

The main interest of this work was the investigation of the transport mechanisms of salmon calcitonin through the epithelial cell monolayer in the presence and absence of pH-sensitive hydrogel nanospheres composed of poly(methacrylic acid-grafted-poly(ethylene glycol)) (PMAA-g-EG). For this purpose, a gastrointestinal cell culture model, the Caco-2 cell line, was employed. The transport of other macromolecules such as fluorescein sodium, fluorescein isothiocyanate dextran, and (14)C-mannitol were also investigated and compared. Transport experiments were conducted in the apical-to-basolateral direction at 37 and 5 degrees C and from the basolateral-to-apical direction at 37 degrees C. Results revealed that the presence of P(MAA-g-EG) nanospheres increased the transport of paracellularly transported molecules such as (14)C-mannitol and fluorescein isothiocyanate dextran when compared to controls. Fluorescein sodium salt solutions were investigated as an actively transported molecule. The transport of fluorescein was affected by the concentration of PEG chains in the structure. Salmon calcitonin transport was enhanced in the presence of the nanospheres. The comparison of the transport behavior of dextran and calcitonin revealed that the main transport mechanism for salmon calcitonin through epithelial cell monolayers is predominantly paracellular.

Biological Transport↗