Stable and mucoadhesive, lyophilised, thiolated chitosan xerogels, loaded with insulin for buccal mucosa deliv-
ery, in place of the currently used parenteral route have been developed. The xerogels were backed with impervious ethyl-
cellulose laminate to ensure unidirectional release and also loaded with enzyme inhibitor to enhance insulin permeability
across the buccal mucosa. Characterisation of xerogels using
HNMR confirmed the degree of deacetylation of the syn-
thesised thiolated chitosan. The amount of thiol groups immobilised on the modified chitosan was quantified by Ellman’s
reaction and molecular weight monitored by gel permeation chromatography. The stability of the secondary structure of
insulin was examined by attenuated total reflectance Fourier transform infra-red spectroscopy and circular dichroism.
permeation studies were undertaken by using EpiOral
and sheep buccal membrane respectively. Insu-
lin released from thiolated chitosan xerogels, loaded with aprotinin (enzyme inhibitor and permeation enhancer) showed a
1.7-fold increase in permeation through EpiOral
buccal tissue construct compared to the pure drug. However, permea-
tion was decreased for xerogels containing the enzyme inhibitor glutathione. Further, aprotinin containing xerogels en-
hanced insulin permeation through sheep buccal membrane and demonstrated good linear correlation with the permeation
data from the EpiOral
study. The results show the potential application of lyoph
ilised thiolated chitosan xerogels con-
taining aprotinin with improved mucoadhesion, penetration enhancing and enzyme inhibition characteristics for buccal
mucosa delivery of macromolecules such as insulin.
Keywords: Buccal mucosa, chitosan, enzyme inhibitor, insulin, permeation enhancement, xerogel.
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