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. 2009 Dec;98(12):4818-30.
doi: 10.1002/jps.21783.

The role of mucoadhesion of trimethyl chitosan and PEGylated trimethyl chitosan nanocomplexes in insulin uptake

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The role of mucoadhesion of trimethyl chitosan and PEGylated trimethyl chitosan nanocomplexes in insulin uptake

Anchalee Jintapattanakit et al. J Pharm Sci. 2009 Dec.

Abstract

The aim of this work was to investigate the role of mucoadhesion in the insulin uptake of nanocomplexes (NC) based of trimethyl chitosan (TMC) and poly(ethylene glycol) (PEG)-graft-TMC copolymers. Self-assembled insulin NC were prepared by polyelectrolyte complexation. The effects of PEGylation and positive charge density on mucoadhesion were assessed using a mucin assay and mucus-secreting HT29-MTX-E12 (E12) monolayers. The behaviors of corresponding insulin NC after adhesion to E12 were also established. All PEGylated TMC copolymers showed significantly higher levels of adhesion to mucus than unmodified TMC. The copolymer composed of 298 PEG chains per TMC macromolecules exhibited the highest level of mucoadhesion, being 3.4 times higher than TMC. The higher mucoadhesive properties of PEGylated TMC copolymers resulted from the synergistic effects of interpenetration of PEG chains into the mucus and electrostatic interaction between positive charged TMC and anionic glycoproteins present in the mucus layer. Compared to TMC, insulin NC based on PEGylated TMC copolymers demonstrated no evidence of insulin uptake improvement due to complete release of insulin from NC after adhering to mucus. CLSM revealed the localization of TMC and its corresponding insulin NC at cell surface membranes of E12.

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