Application of Chitosan-Based Gels in Pharmaceuticals - Chitosan Based Hydrogels: Functions and Applications - page 327

has been to increase drug absorption and the duration of contact time. The most commonly
used approaches to achieve improved drug efficacy are exemplified by the use of viscosi-
fied solutions. Chitosans have superior mucoadhesives owing to their ability to develop
molecular attraction forces by electrostatic interactions with the negative charges of the
mucus [89,90]. In addition, the pseudoplastic and viscoelastic properties [91] of chitosan
solutions make it a potential vehicle for instillation of drugs to the eye.
At present, the use of chitosan in the ophthalmic field is still in the preliminary stages of
investigation. El-Samaligy et al. [92] tested three biodegradable polymers, including chito-
san, to prepare ganciclovir nanoparticles for the treatment of cytomegalovirus retinitis. In
vitro data have shown that drug release from chitosan nanoparticles was encouraging. In
fact, ganciclovir was released for up to 4 days following a first-order pattern. Furthermore,
the release rate was lower for chitosan devices than for the two other polymers (Bovine
serum albumin (BSA) and PEC).
De Campos et al. [93] investigated the potential of chitosan nanoparticles as a new vehi-
cle to improve the delivery of drugs to ocular mucosa. Cyclosporin A (CyA) was chosen
as a model drug. A modified ionic gelation technique was used to produce CyA-loaded
CS nanoparticles. These nanoparticles with a mean size of 293 nm, a zeta potential of
+37 mV, high CyA association efficiency, and loading of 73% and 9%, respectively, were
obtained. The in vitro release studies, performed under sink conditions, revealed the fast
release during the first hour followed by a more gradual drug release during the 24 h
period. The in vivo experiments showed that after topical instillation of CyA-loaded CS
nanoparticles to rabbits, therapeutic concentrations were achieved in the external ocular
tissues (i.e., cornea and conjunctiva) within 48 h while maintaining negligible or unde-
tectable CyA levels in the inner ocular structures (i.e., iris/ciliary body and aqueous
humor), blood, and plasma. These levels were significantly higher than those obtained
following the instillation of a CS solution containing CyA and an aqueous CyA suspen-
sion. The study indicated that CS nanoparticles could be used as a vehicle to enhance the
therapeutic index of the clinically challenging drugs with potential application at the
extraocular level.
7.4.4 Transdermal Drug Delivery
It has been increasingly recognized that intact skin represents an interesting way to pro-
vide controlled delivery of drugs to the systemic circulation. Drugs administered via
transdermal devices approach a zero-order input, which is quite equivalent to the admin-
istration of therapeutic agents after a constant intravenous infusion [94]. In addition,
transdermal administration represents a reliable alternative to oral administration for
substances that are subject to an extensive hepatic first-pass metabolism [95].
Because of its well-known film-forming property, a number of studies have been per-
formed on the usefulness of chitosan membranes as transdermal devices. Thacharodi
and Panduranga Rao [94-96] evaluated the efficacy of chitosan membranes as rate-con-
trolling membranes by testing series of hydrophilic and hydrophobic drugs. They con-
cluded that water-soluble drugs, such as propranolol, could be transported through
chitosan membranes principally via a pore mechanism [94], whereas hydrophobic sol-
utes, such as nifedipine, would be influenced by both partition and pore mechanisms
operating concurrently [96]. The data of Nakatsuka and Andrady are in agreement with
these results since they have suggested that the transport of the hydrosoluble vita-
min < vitamin B 12 > B-12 through cross-linked or blended chitosan films followed pre-
dominantly a pore mechanism [97].