Biomedical Engineering Reference
In-Depth Information
NPs (MSNs) have been considered as promising nanocarriers for
nucleic acid due to their high pore volume and surface area as well
as a loading efficiency over 30 wt%, depending on the drug.
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The
high loading capacity of MSNs allows for a tunable range of drug
loading in particles in order to minimize the side effects and toxicity
induced by the excess use of drug or particles.
3.4
Membrane/Core NPs
To date, only few cases have been reported to have successful
treatment of tumors with systemically delivered siRNA.
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The
development of an efficient nanocarrier system is the much needed
rate-limiting step for RNAi-based therapy. The ideal nanocarrier
for siRNA should protect the cargo from nuclease degradation and
efficiently deliver the siRNA to the cytoplasm where it mediates gene
silencing by inducing degradation of messenger RNAs (mRNAs)
containing the complementary sequence.
Among various delivery systems for RNAi-based therapy,
the most promising non-viral carriers for systemic delivery are the
PEGylated NPs with proper surface modification utilizing multiple
components. The major components for this system are cationic
molecules, such as cationic lipid or polymer, which can interact with
negatively charged nucleic acid to form nano-sized particles.
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20, 79
Proper surface modification with PEGylation and specific ligands
is also important in order to provide prolonged circulation of
the NPs in the system as well as targeted delivery with improved
cellular bioavailability, resulting in higher accumulation in the
target sites. Also, endosomolytic agents, such as fusogenic lipids,
can be incorporated to facilitate intracellular release of nucleic
acid.
20, 80
Such surface modifications are commonly used to avoid
many barriers in systemic delivery and develop an efficient delivery
system.
The RES is a major barrier for NPs after systemic administration.
When NPs are systemically administered, they are immediately
recognized by serum proteins, also known as opsonins, and these NPs
are rapidly taken up by macrophages in the RES, located mostly in
the liver and the spleen.
In the early stages of developing a strategy
to avoid the RES, a pre-dosing method was used. A large excess of
empty carrier was administered first to saturate the RES, followed
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