Application of Chitosan-Based Gels in Pharmaceuticals - Chitosan Based Hydrogels: Functions and Applications - page 325

insulin transport across the colon membrane of rats for nanoparticles made with quater-
nized derivatives than those made of chitosan. In vivo studies in rats have shown enhanced
colonic absorption of insulin by using these nanoparticles compared to free insulin in
diabetic rats [71].
A pH-sensitive multicore microparticulate system containing chitosan microcores
entrapped in enteric acrylic microspheres has been reported [72]. Sodium diclofenac was
efficiently entrapped within these CS microcores and then microencapsulated into Eudragit
L-100 and Eudragit S-100 to form a multireservoir system. An in vitro release study revealed
no release of the drug in gastric pH for 3 h, and after the lag time, a continuous release for
8-12 h was observed in the basic pH.
7.4.3 Mucosal Delivery
Nowadays, mucosal surfaces such as nasal, peroral, and pulmonary are receiving a great
deal of attention as alternative routes of systemic administration. Chitosan has mucoadhe-
sive properties, and, therefore, it is particularly useful in formulating bioadhesive dosage
forms for mucosal administration (ocular, nasal, buccal, gastroenteric, and vaginal-uterine
therapy) [73]. Nasal mucosa has high permeability and easy access of drug to the absorp-
tion site. The particulate delivery to peroral mucosa is easily taken up by Peyer's patches of
the gut-associated lymphoid tissue. Chitosan has been found to enhance the drug absorp-
tion through mucosae without damaging the biological system. Here, the mechanism of
action of chitosan was suggested to be a combination of bioadhesion and a transient wid-
ening of the tight junctions between epithelial cells [74].
7.4.3.1 Nasal Delivery
Nasal drug delivery represents an interesting alternative to the parenteral route for admin-
istration of drugs that show poor oral bioavailability, such as peptides and proteins. In addi-
tion, the nose has a further advantage for the absorption of drugs in that it has a large
epithelial surface area available due to the presence of numerous microvilli. On the other
hand, one of the major drawbacks of the nasal cavity is its rapid mucociliary clearance mech-
anism, which can reduce the bioavailability of drugs given intranasally. A possible strategy
to circumvent this problem, without using absorption enhancers, is to prevent the clearance
of the delivery system from the nasal cavity and thereby prolong contact between the drug
and the mucosa. This aim can be reached by employing bioadhesive systems that form a gel-
like structure at the contact of the mucus [75]. Chitosan is able to swell and form a gel-like
layer in an aqueous environment (here, e.g., by absorbing water from the mucous layer in the
nasal cavity), which is favorable for the interpenetration of polymer and glycoprotein chains
of the mucus.
Mucoadhesive microspheres composed of hydroxypropyl methylcellulose, chitosan, car-
bopol 934P (and a combinations of polymers) [76], and chitosan-poly(methyl vinyl ether- co -
maleic anhydride)-microparticles were prepared by spray drying, for the nasal delivery of
propranolol HCl. These microspheres affected the integrity of tight junctions, without
causing cell damage, relative to their swelling and charge of polymer. Cell viability was
not affected, except with chitosan, but this was recoverable [77].
An emulsifying method used for the production of ethylcellulose-CMs suitable for the
nasal delivery of loratadin was shown to result in improved drug entrapment and moderate
swelling, compared with conventional CMs [78]. Chitosan-4-thiobutylamidine (TBA) micro-
spheres have also displayed the controlled release of fluorescein isothiocyanate-labeled