Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 297

and avoid drug release and absorption in the stomach (pH 1-3) unless the system reaches
the colon. The release of drug can be triggered by specific hydrolysis of the polymer matrix
in the colon or the enzymatic reactions by colonic flora there. Chitosan is biodegradable by
colonic bacterial flora; thus it is a commonly used polymer for colon drug delivery.
Particles of chitosan/pectin PEC particles were prepared by complex coacervation from
chitosan and pectin dispersions [164]. By adding acetate phthalate into the system, the
formulation presented the slowest triamcinolone release rate, of only 1.33%, in acidic
medium after 2 h, which reduced the drug release in gastric juice. Therefore, particles
selectively release their contents in colon sites where the crucial condition to allow drug
release remain on the enzymatic degradation of polysaccharides by the specific colonic
flora.
Proteins can also be delivered to the colon using a chitosan-based hydrogel carrier.
Chitosan-alginate beads loaded with BSA were studied to explore the protection of protein
against acidic and enzymatic degradation during gastric passage [165]. The beads showed
no sign of erosion in gastric fluid, whereas they were found to erode, burst, and release the
protein in intestinal fluid.
In addition, some chitosan derivatives show excellent association with insulin and
improved its intestinal absorption to a great extent. Nanoparticles were prepared by the
polyelectrolyte complexation method using chitosan, triethylchitosan, and dimethyl-
ethylchitosan for colon delivery of insulin [166]. These nanoparticles carried positive
charges and showed a size distribution in the range of 170-270 nm. Insulin loading was
more than 80% for all the nanoparticles. Insulin release showed a small burst effect at
the beginning and then a sustained release characteristic for 5 h. Also better insulin
transport across- the colon membrane of rats was found for nanoparticles made of quat-
ernized derivatives than for those made of chitosan. In vivo studies in rats have shown
enhanced colon absorption of insulin by using these nanoparticles compared to free
insulin in diabetic rats [166].
6.7.5 Ocular Drug Delivery
In ocular drug delivery, the major problem is to maintain an effective drug concentration
at the site of action for an appropriate period of time in order to achieve the expected
pharmacological response. Essential protective mechanisms of the eye, such as effective
tear drainage, blinking, and low permeability of the cornea, prevent the success. Many
attractive properties, such as mucoadhesive character, penetration-enhancing property,
and cellular permeability, of chitosan allow it to be a very promising polymer for ocular
drug delivery [167].
A novel in situ forming gel composed of chitosan and gellan gum was developed as an
ocular DDS. The gelation was triggered by dual physiological mechanisms (pH and ion-
activated gelation). Timolol maleate, the drug that is frequently used for glaucoma therapy,
was used as a model drug to check the efficacy of the formulation. Clarity, gelation pH,
isotonicity, sterility, viscosity, transcorneal permeation profile, and ocular irritation of the
formulation have all been investigated. A significant increase in ocular retention time of
this vehicle was observed. The developed system can be a viable alternative to conven-
tional eye drops for the treatment of various ocular diseases and is suitable for clinical
application [168].
Peptu et al. [169] prepared gelatin/chitosan microparticles for ocular drug delivery by a
two-step cross-linking process performed in an emulsion-phase separation system.