Effect of PEGylation on the toxicity and permeability enhancement of chitosan

Casettari, Luca, Vllasaliu, Driton, Mantovani, Guiseppe , Howdle, Steven M., Stolnik, Snow and Illum, Lisbeth (2010) Effect of PEGylation on the toxicity and permeability enhancement of chitosan. Biomacromolecules, 11 (11). pp. 2854-2865. ISSN 1525-7797

Full content URL: http://dx.doi.org/10.1021/bm100522c

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Item Type:Article
Item Status:Live Archive


The aim of the present work is to investigate if conditions can be devised where PEGylation of chitosan would reduce its toxicity toward the nasal mucosa while maintaining its ability to open the cellular tight junctions and, consequently, produce an enhancement of macromolecular permeability. A series of mPEG-g-chitosan copolymers with varying levels of mPEG substitution, mPEG molecular weight, and chitosan molecular weight were synthesized by grafting carboxylic acid-terminated mPEGs (M w 1.9 and 5.0 × 10 3 g mol -1) to chitosans (M w 28.9 and 82.0 × 10 3 g mol -1) using a NHS/EDC coupling system. The synthesized mPEG-g-chitosans were fully characterized using a number of techniques, including FT-IR, 1H NMR, and SEC-MALLS and their physicochemical properties were analyzed by TGA and DSC. Thereafter, the conjugates were tested for their cytotoxicity and tight junction modulating property in a relevant cell model, a mucus producing Calu-3 monolayer. mPEG-g-chitosan conjugates exhibited reduced toxicity toward cells, as compared to unmodified chitosan counterparts. Furthermore, the conjugates demonstrated a dramatic effect on cell monolayer transepithelial electrical resistance (TEER) and enhancement of permeability of model macromolecules. TEER and permeability-enhancing effects, as measurable indicators of tight junction modulation, were found to be pH-dependent and were notably more pronounced than those exhibited by unmodified chitosans. This work therefore demonstrates that conditions can be contrived where PEGylation improves the toxicity profile of chitosan, while preserving its effect on epithelial tight junctions in the nose.

Keywords:Cell monolayers, Permeability enhancement, Reduced toxicity, Tight junctions, Transepithelial electrical resistance
Subjects:B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
Divisions:College of Science > School of Pharmacy
ID Code:6850
Deposited On:16 Nov 2012 12:24

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