NDLI: N-Trimethyl Chitosan Chloride as a Potential Absorption Enhancer Across Mucosal Surfaces: In Vitro Evaluation in Intestinal Epithelial Cells (Caco-2)

Content Provider	Springer Nature Link
Author	Kotzé, Awie R Lueβen, Henrik L. de Leeuw, Bas J. de Boer, ABert G. Verhoef, J. Coos Junginger, Hans E.
Copyright Year	1997
Abstract	Purpose. Previous studies have established that chitosan hydrochloride and glutamate are potent absorption enhancers for large hydrophilic compounds across mucosal surfaces. However, these compounds lack solubility at neutral pH values. A partially quaternized and well-soluble derivative of chitosan, N-trimethyl chitosan chloride, was synthesized and the effects of this polymer on the transepithelial electrical resistance and permeability of intestinal epithelial cells were investigated in vitro. Methods. N-trimethyl chitosan chloride was synthesized by reductive methylation and characterized with NMR. The effect of this polymer (1.0−2.5% w/v) on the transepithelial electrical resistance of intestinal epithelial cells, using Caco-2 cell monolayers, was investigated. Permeation of the hydrophilic model compounds [$^{l4}$C]-mannitol (MW 182.2), FITC-Dextran (MW 4400) and the peptide drug buserelin (MW 1299.5), in the presence of N-trimethyl chitosan chloride (1.5−2.5% w/v), was followed for 3 hours. The transport process of the fluorescent marker, FITC-Dextran 4400, across the cell monolayers was visualised with confocal laser scanning microscopy. Viability of the cells was checked with the trypan blue exclusion technique. Results. N-trimethyl chitosan chloride was found to be a perfectly water-soluble, partially quaternized (about 12%) derivative of chitosan. This polymer (1.5−2.5% w/v) caused a pronounced and immediate reduction (25−85%) in the transepithelial electrical resistance of Caco-2 cells. Large increases in the transport rate of [$^{!4}$C]-mannitol (32−60 fold), FITC-Dextran 4400 (167−373 fold) and buserelin (28−73 fold) were demonstrated. Confocal laser scanning microscopy confirmed that N-trimethyl chitosan chloride opens the tight junctions of intestinal epithelial cells to allow increased transport of hydrophilic compounds through the paracellular transport pathway. No deleterious effects to the cells could be demonstrated with trypan blue. Conclusions. The potential use of N-trimethyl chitosan chloride as an absorption enhancer across mucosal surfaces could be an important contribution towards the development of effective delivery systems for hydrophilic drugs.
Starting Page	1197
Ending Page	1202
Page Count	6
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	14
Issue Number	9
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1997-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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