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(1)
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. In vitro
and ex vivo 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.