Biomedical Engineering Reference
In-Depth Information
delivery system for both cellular and systemic delivery has to be
devised. An ideal gene delivery system should accomplish physical
and chemical stability of both the nucleic acid and its vehicle,
along with biocompatibility and the capability of transferring
exogenous nucleic acid into the target sites with a low risk of
immunogenicity and other toxicity.
1
Other considerations that have
to be taken into account in developing effective nanocarriers are
cellular internalization, endosomal escape, and release of nucleic
acid molecules into the cytosol.
24
Two major carrier systems that show several advantages over
the delivery of naked nucleic acid molecules have been developed.
These carrier systems are viral and non-viral delivery systems.
A viral carrier system using several viruses such as retrovirus,
adenovirus, and adeno-associated virus (AAV) has shown efficient
transfection properties both
. Viruses are used
because of their ability to allow their genomes to penetrate into the
target cell's cytoplasm, which may be quite beneficial in overcoming
the problem of nucleic acid delivery.
in vitro
and
in vivo
22
However, there is a risk of
causing side effects, including immune and toxic responses, random
integration of vector DNA into the host chromosome, specific tissue
tropism, and potential recombination with wild-type viruses.
1
Therefore, a non-viral delivery system is preferred in gene therapy
despite its relatively low efficiency of gene transfer compared with
viral carriers. However, recent advances in nanotechnology have
significantly increased the gene transfer efficiency of non-viral
vectors.
3.2
Challenges in Nanocarrier Systems
Nanotechnology has been continuously applied in the area of
non-viral drug delivery in order to develop NPs that can provide
improved protection of unstable drugs, such as nucleic acids, for
enhanced bioavailability and prolonged therapeutic effects. To
study the therapeutic effect and toxicity of NPs, it is essential to
understand their pharmacokinetics (PK) profiles and biodistribu-
tion. The PK and biodistribution of NPs may be critically affected by
their chemical and physical properties such as size, surface charge,
and shape. NPs smaller than 5 nm may be rapidly cleared by the
kidney.
25, 26
Accumulation of larger NPs (greater than 10 nm in size)
is often observed in the liver, spleen, and bone marrow because of the
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