Future - Chitosan Based Hydrogels: Functions and Applications - page 468

10.2.2 extracellular Carriers
Chitosan is a linear polysaccharide composed of randomly distributed N -acetyl-d-
glucosamine and β-(1,4)-linked d-glucosamine. Compared with polyethyleneimine (PEI)
(another well-studied polymer with generally high transfection efficiency but significant
cytotoxicity), chitosan has lower transfectability. This is believed to be related to its com-
paratively weak endolysosomalytic proton sponge effect.
Park et al. [11] have used galactosylated chitosan-graft-poly(ethylene glycol) (GCP) as a DNA
vector. The particle size of GCP-DNA complexes is small, with a minimal value of about
27 nm. DNA complexed with GCP is stable and protected against enzyme degradation with
DNase. However, the transfection efficiency when using GCP-DNA complexes is very low,
mainly because of interaction with plasma leading to dissociation of GCP-DNA complexes.
Our previous studies have proposed a DNA- N -dodecylated chitosan complex and salt-
induced gene delivery (CS-12) from dodecyl bromide and chitosan (average molecular
weight 700 kDa), assembled with DNA (salmon testes, average molecular weight 2 kbp) to
form DNA-CS-12 polyelectrolyte complex [12]. Incorporating dodecylated chitosan can
enhance the thermal stability of DNA. Pure DNA in the absence of dodecylated chitosan
is hydrolyzed by DNase and can be broken into fragments. On the other hand, DNA dis-
sociated from the complex is well protected and remains intact due to the protection from
DNase offered by alkylated chitosan.
10.2.3 intelligent Carriers
Chitosan-based environmentally sensitive hydrogels have enormous potential for various
applications. Some environmental variables, such as low pH and elevated temperatures,
are found in the body. For this reason, either pH-sensitive and/or temperature-sensitive
hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are respon-
sive to specific molecules, such as glucose or antigens, can be used as biosensors as well as
drug delivery systems.
If bonding between the therapeutic and hydrogel polymer is established by an enzyme-
sensitive tether and broken by the specific enzyme produced during normal cell activity in
or around the hydrogel, a “smart” drug delivery system (DDS) is created and its drug
release is more specific to the target tissue. For example, a vascular endothelial growth
factor (VEGF) can be covalently immobilized within a hydrogel network by enzyme-sen-
sitive oligopeptides [13]. The release of VEGF is mediated by proteases (e.g., matrix metal-
loproteinases) secreted by migrating cells. The cell-demanded VEGF release matches the
release profiles with the cellular activity that is critical during tissue regeneration.
A thermosensitive chitosan-Pluronic hydrogel was also produced by ultraviolet (UV)
photo-cross-linking [14]. The chitosan and Pluronic groups were functionalized with pho-
tosensitive acrylate groups that were cross-linked by UV exposure. The resultant polymers
could then form a physical network at temperatures above the low critical solution tem-
perature (LCST). The hydrogel showed the sustained release of encapsulated human
growth hormone and plasmid DNA, demonstrating its potential usefulness for preparing
different types of drugs [14,15].
Numerous studies on DNA delivery with chitosan as a carrier biomaterial have shown
effective expression of reporter genes in vitro and in vivo [16-18], promoting chitosan as an
attractive candidate for siRNA delivery.
Chitosan can not only transfer plasmid DNA, but can also deliver RNA. Because of this,
chitosan is useful for alleviating poor cellular uptake and rapid degradation of naked