Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 291

glucose to gluconic acid in the presence of oxygen. The formation of the acid results in a
decrease in pH; this triggers swelling in pH-sensitive chitosan hydrogels, thereby causing
changes in its pore size and consequently facilitating the release of insulin by the diffu-
sion-mediated process [142].
Recently, Manna et al. fabricated a multilayer thin film of PVA-borate and chitosan. This
film was glucose sensitive and its disintegration was observed in the presence of glucose.
The mechanism of glucose-triggered multilayer membrane degradation was discussed by
the author. In the presence of glucose, borax molecules prefer to complex with glucose
rather than PVA hydroxyl groups and thus the physically cross-linked gel loses its gelation
behavior. As a result, glucose disintegrates the physically cross-linked PVA-borate com-
plex, as shown in Figures 6.17 [143]. The glucose-triggered release of an anticancer drug,
doxorubicin, from the multilayer thin film was also studied, as it is well known that cancer
cells possess high concentrations of glucose. The results showed that at higher concentra-
tions of glucose, complete disassembly of the multilayer thin film occurred and this caused
the release of the drug. Therefore, this chitosan-based thin film can be utilized to target
anticancer therapeutics release in cancer cells.
6.6.3 Targeted Drug release
Drugs can be released from a hydrogel over a period of time in a controlled manner. The
process could be a time-controlled one or an environmental stimuli-triggered one as men-
tioned above. However, in order to achieve a more specific or a more accurate administra-
tion, targeted release systems appear. These systems protect the specific drug until it
reaches the desired location (e.g., a tumor or a specific organ) where the drug is released in
a controlled way. This strategy could revolutionize the delivery of drugs and has the poten-
tial not only to reduce the amount of drug required to obtain effective therapy, but also to
virtually eliminate nonspecific side effects.
Targeted drug delivery can be used to treat many diseases, such as cardiovascular dis-
eases and diabetes. However, the most important application of targeted drug delivery is
to treat cancerous tumors.
A targeted DDS is comprised of three components: a therapeutic agent, a targeting moi-
ety, and a carrier system [144]. The environmental stimuli mentioned above can also be
used as signals (targeting moiety) for targeting application. One can find an example of a
pH-sensitive chitosan-based hydrogel used as a colon-specific DDS in Section 6.6.2.1. Such
a DDS is known as a kind of physical targeted DDS. Apart from this, there are still two
kinds of targeted drug delivery: active targeted drug delivery, such as some antibody
medications; and passive targeted drug delivery, such as the enhanced permeability and
retention (EPR) effect.
6.6.3.1 Passive Targeting: EPR Effect
Passive targeting is based on the EPR effect of the vasculature surrounding tumors, which
can lead to the selective accumulation of macromolecular drugs in tumor tissues [145].
This specific passive accumulation of macromolecules was attributed to defective tumor
vasculature with disorganized endothelium at the tumor site and a poor lymphatic drain-
age system. Researchers have taken advantage of this characteristic to deliver various
drugs by encapsulating them within nanoparticles or conjugating them with polymers.
Today, it is evident that long circulating macromolecules and nanosized particulates
accumulate passively at the tumors due to the EPR effect [144].