title: Cellular Uptake and Intracellular Cargo Release From Dextran Based Nanogel Drug Carriers.
abstract: Nanogels (NG) hold great promise as a drug delivery platform. In this work, we examine the potential of lysozyme-dextran nanogels (LDNG) as drug carriers in vitro using two cell lines: a model target tissue, human umbilical cord vein endothelial cells (HUVEC) and a model of the mononuclear phagocyte system (phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells). The LDNG (∼100 nm) were prepared with rhodamine-label dextran (LRDNG) via Maillard reaction followed by heat-gelation reaction and were loaded with a fluorescent probe, 5-hexadecanoylaminofluorescein (HAF), as a mock drug. Epifluorescence microscopy confirmed rapid uptake of LRDNG by HUVEC. Although LysoTracker Green staining indicated a lysosomal fate for LRDNG, the mock drug cargo (HAF) diffused extensively inside the cell within 15 min. Flow cytometry and confocal microscopy indicated slow uptake of LRDNG in PMA-stimulated THP-1 cells, with only 41% of cells containing LRDNG after 24 h exposure. Finally, 24 h exposure to LRDNG did not affect the viability of either cell type at the dose studied (20μg/ml). At a higher dose (200μg/ml), LRDNG resulted in a marked loss of viability of HUVEC and THP-1, measuring 30% and 38%, respectively. Collectively, our results demonstrate the great potential of LRDNG as a drug delivery platform, combining simple production, rapid uptake and cargo release in target cells with "stealth" properties and low cytotoxicity.
authors.affiliation: Department of Anesthesiology and Critical Care and Department of Materials Science and Engineering, University of Pennsylvania , Philadelphia, PA 19104.
authors.forename: M
authors.initials: M
authors.lastname: Carme Coll Ferrer
authors.forename: Peter
authors.initials: P
authors.lastname: Sobolewski
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Composto
authors.forename: David M
authors.initials: DM
authors.lastname: Eckmann
keywords: HUVEC; THP-1; dextran; drug delivery; lysozyme; nanogel
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