Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 298

Diameters of the particles were 0.202-4.596 μm. Adrenalin was used as the drug to be
delivered. The in vivo adrenalin ocular delivery was tested on both animals and a volun-
tary human patient to determine the adrenalin action and by tears. The particles showed
good adherent properties without irritation to the patient; adrenalin was released and this
cleared the ocular congestion.
Nanocarriers are frequently used for ocular drug delivery, mainly because of their capac-
ity to protect the encapsulated molecule while facilitating its transport to different com-
partments of the eye [167]. Chitosan nanoparticles with an average diameter of 280 nm,
developed by modified ionic gelation of chitosan with TPP, were fabricated to prolong IM
precorneal residence time and to improve its ocular bioavailability. Release studies showed
a small initial burst release during the first hour followed by slow sustained drug release
of 76% from nanoparticles during a 24 h period. According to the author, the chitosan
nanocarriers developed were able to contact intimately with the cornea, providing slow
gradual IM release with long-term drug level and thereby increasing delivery to both
external and internal ocular tissues [170].
6.7.6 Transdermal Drug Delivery
The transdermal route is an attractive alternative to deliver therapeutic drugs. The possi-
ble benefits of transdermal drug delivery include the following: drugs can be delivered for
a long duration at a constant rate, drug delivery can be easily interrupted on demand by
simply removing the devices, and drugs can bypass hepatic first-pass metabolism [110].
Furthermore, drug carriers in the form of hydrogels are preferred because of their high
water content, providing a comfortable feeling on the patient's skin in comparison with
conventional ointments and patches.
Glimepiride, an antidiabetic sulfonylurea drug, often has adverse effects and bio-
availability problems due to its poor solubility when delivered via the oral route. A trans-
dermal delivery system for glimepiride was developed by using chitosan film as a drug
vehicle. In order to optimize drug delivery and circumvent the skin barrier function, inclu-
sion complexation of glimepiride with β-cyclodextrin was used in the formulation.
Permeation studies through rat abdominal skin showed that high drug flux values were
obtained from films containing glimepiride-β-cyclodextrin complex. More importantly,
an evident therapeutic efficacy sustained for about 48 h was obtained on diabetic rats
treated with this chitosan transdermal delivery system [171].
Recently, Lee et al. [172] prepared multifunctional core-shell polymeric nanoparticles for
transdermal DNA delivery. The developed nanoparticles comprised a hydrophobic PLGA
core and a positively charged glycol chitosan shell. Fluorescent quantum dots (QDs) were
loaded in the core for ultrasensitive detection of Langerhans cell (LC) migration following
transdermal delivery. An emulsion-diffusion-evaporation method was used to fabricate
the QD-loaded nanoparticles, while a reporter gene was electrostatically adsorbed onto the
glycol chitosan shell layer by mixing the nanoparticles with DNA. Chitosan-based nano-
particles can rapidly release a significant amount of their loaded DNA at pH 7.4 while being
minimal at pH 6.0, indicating a pH-mediated mechanism. In addition, the mouse model
study demonstrated that bombardment of nanoparticles transfected DNA directly into LCs
present in the epidermis; the transfected LCs then migrated and expressed the encoded
gene products in the skin draining lymph nodes, as shown in Figure 6.18 [ 172]. Thus, the
developed nanoparticles have potential use in immunotherapy and vaccine development.