Dextran-pegylated microparticles for enhanced cellular uptake of hydrophobic drugs

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 84; no. 3; pp. 540 - 548
• Main Authors: Cassano, Roberta, Ferrarelli, Teresa, Schätzlein, Andreas G., Uchegbu, Ijeoma F., Trombino, Sonia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2013
• Subjects: Caco-2 Cells; Cell Line; Dextran; Dextrans - chemistry; Drug Carriers - chemistry; Drug Design; HT29 Cells; Humans; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydrophobic drugs; Inhibitory Concentration 50; Ketoconazole - administration & dosage; Ketoconazole - chemistry; Microscopy, Confocal; Microscopy, Electron, Scanning; Microspheres; Mucoadhesion; Mucus - drug effects; Polyethylene glycol; Polyethylene Glycols - chemistry; Polymeric microspheres; Polymers - chemistry; Spectroscopy, Fourier Transform Infrared; Time Factors; Uptake studies; Water - chemistry; Dextran; Uptake studies; Hydrophobic drugs; Polymeric microspheres; Mucoadhesion; Polyethylene glycol
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2013.01.017

Polymeric mucoadhesive systems based on dextran and polyethylene glycol were prepared for the oral controlled release of a hydrophobic model drug. Though mucus is a barrier, the presence of PEG and dextran chains could have potentiated the consolidation stage of mucoadhesion by increasing microspheres–mucus interaction. Polyethylene glycol monosubstituted with a polymerizable acrylic moiety was linked to 6-carboxy free position on dextran side chains and then subjected to radical polymerization with a comonomer in order to obtain microspheres for the oral controlled release of ketoconazole, a hydrophobic model drug. Microparticles were submitted to studies on their ability to absorb and retain water. Cell uptake studies, in the presence and absence of mucus, across two different monolayers, respectively, HT29-MTX-E12 and Caco-2, were done. Cytotoxicity studies were carried out to calculate the IC50 value. The ability of microspheres to open monolayers tight junctions was tested by measuring their TEER values. Images of cell uptake were visualized by CLSM. In HT29-MTX-E12 cells, more mucoadhesion and drug internalization is seen thanks to the presence of PEG and dextran chains.