Preparation and in vitro evaluation of thiolated chitosan microparticles

The objective of this study was to prepare a microparticulate drug delivery system being based on a
new thiomer, namely a chitosan 2-iminothiolane conjugate (chitosan-TBA conjugate). Due to
thiol groups being immobilized on chitosan, chitosan-TBA conjugate exhibits improved mucoadhesive
and permeation enhancing properties. Because of these features microparticulate drug delivery systems
based on chitosan-TBA conjugate might be a promising tool for the non-invasive administration
of hydrophilic macromolecular drugs. Chitosan-TBA conjugate microspheres were prepared
by the emulsification/solvent evaporation method. Fluorescein-isothiocyanate labelled dextran
(FITC-dextran) was chosen as a model hydrophilic drug. Microspheres have been characterized by
morphological analysis, thiol group content, swelling behaviour, polymer degradation drug load
determination, dissolution test and mucoadhesion studies. Results reported in this work demonstrated
the possibility to obtain stable microspheres without cross-linking agents. Thiolated chitosan
microspheres seem to be more stable in aqueous media with respect to unmodified chitosan.
The degradability by lysozyme appears quite similar for both polymers, showing that chemical
modification does not influence the biodegradable properties of chitosan. Microspheres were able to
control the drug release for at least 1 h, exhibiting comparatively strong mucoadhesive properties.
The chitosan-TBA conjugate microparticles remain on the mucosa in a 2.5-fold higher concentration
with respect to unmodified chitosan microparticles. These data suggest that chitosan-TBA conjugate
microspheres have the potential to be used as a mucoadhesive drug delivery system.