Dextran-pegylated microparticles for enhanced cellular uptake of hydrophobic drugs.

TitleDextran-pegylated microparticles for enhanced cellular uptake of hydrophobic drugs.
Publication TypeJournal Article
Year of Publication2013
AuthorsCassano R, Ferrarelli T, Schätzlein AG, Uchegbu IF, Trombino S
JournalEur J Pharm Biopharm
Volume84
Issue3
Pagination540-8
Date Published2013 Aug
ISSN1873-3441
KeywordsCaco-2 Cells, Cell Line, Dextrans, Drug Carriers, Drug Design, HT29 Cells, Humans, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Inhibitory Concentration 50, Ketoconazole, Microscopy, Confocal, Microscopy, Electron, Scanning, Microspheres, Mucus, Polyethylene Glycols, Polymers, Spectroscopy, Fourier Transform Infrared, Time Factors, Water
Abstract

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.

DOI10.1016/j.ejpb.2013.01.017
Alternate JournalEur J Pharm Biopharm
PubMed ID23419813