Biomedical Engineering Reference
In-Depth Information
Systemic (IgG) and local (IgA) immune responses against diphtheria toxoid associated
with chitosan microparticles were strongly enhanced after oral delivery in mice.
Furthermore, dose-dependent systemic immune responses could be elicited and enough
antitoxin was produced to protect against the harmful effects of the diphtheria toxin [15].
Chitosan-alginate microcapsules are found to be an effective means of protecting immu-
noglobulin (IgY) from gastric inactivation, allowing its use for the widespread prevention
and control of enteric diseases [16].
Cancer is a disease state in which the cells in our body undergo mutations at the genetic
level and are transformed, acquiring the ability to replicate limitlessly. Conventional can-
cer treatment involves the use of surgery and cytotoxic chemotherapy and/or radiotherapy,
which have the potential for harming normal, otherwise healthy, nonneoplastic cells.
Newer forms of therapy such as immunotherapy and gene therapy have shown initial
promise due to the treatment of a wide range of diseases, both inherited and acquired [17],
but still require better ways to limit exposure to cancerous lesions in the body.
3.1.1.2 Chitosan as a Gene Vector
The basic concept underlying gene therapy is that human disease may be treated by the
transfer of genetic material into specific cells of a patient in order to correct or supplement
defective genes responsible for disease development. Gene therapy is currently being
applied in many different health problems such as cancer, AIDS, and cardiovascular dis-
eases. Recently, the key research aim of gene therapy is to search for effective and safe
vector systems. The main systems for gene delivery are both viral and nonviral vectors.
Although viral vectors show high transfection efficiency, many drawbacks limit their
applications, such as oncogenic effects, nonspecificity, immunogenicity to the target cells,
and degradation by enzymes [18]. Nonviral vectors for gene therapy are preferred as safer
alternatives to viral vectors. They have many advantages, including safety, stability, and
lower immunogenicity [19]. Currently, the two main types of nonviral gene delivery vec-
tors are cationic liposomes and cationic polymers [20,21].
Cationic liposomes have potential as a gene delivery vector. However, their applications
are limited to local delivery due to low stability and rapid degradation in the body [22,23].
Cationic polymers have been used to deliver DNA both
in vitro
and
in vivo
in terms of bio-
compatibility, low cytotoxicity, and cost-effectiveness [24]. As a natural cationic polymer,
chitosan has been widely employed in gene delivery due to its biocompatibility, biode-
gradability, low immunogenicity, and nontoxic material [25]. Chitosan protonated in acidic
conditions can form complex nanoparticles with anionic DNA by electrostatic interactions
[26] and protect it against nuclease degradation [27]. Also, the mucoadhesive property of
chitosan potentially permits a sustained interaction between the macromolecules and an
efficient uptake [28-30]. Chitosan has the ability to open intercellular tight junctions, facili-
tating its transport into the cells [31]. It has the advantage of not requiring sonication and
organic solvents for its preparation, therefore minimizing possible damage to DNA during
complexation. However, chitosan as a gene vector still has some disadvantages such as
relative inefficiency and low specificity [32].
The first report suggesting the probable candidature of chitosan as a gene delivery agent
was published in the year 1998 [33]. Chitosan self-aggregate-DNA complexes achieved an
efficient transfection of chitooligosaccharide-1 (COS-1) cells and the level of expression
with plasmid-chitosan was observed to be no less than that with plasmid-lipofectin com-
plexes in SOJ cells. A few years later, Mao et al. [34] reported the preparation of chitosan-
DNA nanoparticles using a complex cooperation process. They investigated important
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