Application of Chitosan-Based Gels in Pharmaceuticals - Chitosan Based Hydrogels: Functions and Applications - page 323

Recombinant Streptococcus mutans glucan-binding protein D has also been incorporated
into PLGA microspheres for intranasal administration, and was then surface coated with
chitosan. The microspheres were shown to be potentially useful for antigen delivery in
dental caries vaccination in rats [54].
Adenoviral vectors were encapsulated into a microparticulate system for mucosal deliv-
ery. Microencapsulation of the vectors was performed by ionotropic coacervation of chito-
san, with bile salts as counteranions. Not only was the adenovirus protected from the low
pH of the external medium, but also its release was delayed and dependent on cell contact,
which is an advantage for mucosal vaccination purposes. The adenoviral infectivity was
maintained and the onset of delivery was host-controlled [55].
For the future development of microparticles for oral vaccine delivery, a modified-cell
in vitro model has been developed. Using this model, commercially available FluoSpheres ®
(Molecular Probes, Inc.) and CMs (1.7 μm) have been shown to be transported at a signifi-
cantly higher amount by the human modified-cell model than when transported using
a Caco-2 cell monoculture [56,57]. This in vitro model improves the study of targeting
modified-cells of human origin.
7.4.2 Oral Drug Delivery
The oral route is the most popular and the most practical way to administer a therapeutic
agent, particularly from the point of view of the patient. However, it is not always the most
suitable route for some active compounds, such as nonsteroidal antiinflammatory drugs,
which cause gastric mucosal damage; for drugs poorly absorbed, such as peptides; or for
drugs that undergo an extensive first-past effect (e.g., nitroglycerin, alprenolol, fluorouracil,
and desipramine) [58]. Furthermore, the possibility to control drug delivery after oral
administration is very limited since it depends on the residence time of the dosage in the GI
tract. Indeed, the drug will follow the gastric emptying rate, a physiological parameter that
is subject to significant interindividual variability [59]. For these reasons, researchers have
tried new excipients for manufacturing tablets or to develop drug carrier systems capable
of controlli ng drug delivery after oral admi nistration (e.g., microparticles). For several years,
chitosan has been largely evaluated as a potential vehicle for drugs administered orally.
7.4.2.1 Gastric Delivery
The main function of the stomach is to digest food and deliver chyme to the intestine. The
gastric motor activities cause the emptying process of the gastric contents. A successful
gastric retention delivery system should be able to overcome the housekeeper waves and
remain in the stomach during the fasted state.
Floating hollow chitosan microspheres would be an interesting gastroretentive
controlled-release delivery system for drugs. The oral administration of tetracycline chito-
san microspheres prepared by chemical cross-linking in fasted gerbils shows that they pro-
vide a longer residence time than either tetracycline solution or microspheres prepared by
ionic precipitation [60].
The release of the drug from floating microcapsules containing melatonin prepared by the
ionic interaction of chitosan and sodium dioctyl sulfosuccinate was greatly retarded in sim-
ulated gastric fluid, and the microspheres maintained their integrity for more than three
days compared with nonfloating microspheres, where drug release was almost instant [61].
A stomach-specific drug delivery system using chitosan microspheres has been devel-
oped to increase the efficacy of tetracycline against Helicobacter pylori by ionic cross-linking