Biomedical Engineering Reference
In-Depth Information
The resulting particulate system is a calcium phosphate particle with some nucleic
acid on the interior of the particle, but the majority on the exterior (surface decora-
tion). The problem with this scheme is the lack of protection of the nucleic acid
from enzymatic attack.
Calcium phosphate-DNA particles in the 10-20 nm size range are synthesized
using the coprecipitation method but degradation of the DNA is evident (Welzel
2004
). In addition, the use of DNA as a dispersant proves unsuccessful as agglom-
eration tends to occur in serum-containing media resulting in decreased bioavail-
ability. Improvements to this scheme (single-shell method) are made by the
triple-shell approach. Agglomeration is avoided for the triple-shell method and
DNA transfection efficiency is comparable to that of commercially available
Polyfect (Sokolova
2006b, 2007a,b, 2010
) but only when serum proteins are absent.
Agglomeration takes place in the presence of proteins. Thus, the major limitation
of the triple layer method is the likelihood of agglomeration in an
in vivo
model
where serum proteins naturally exist in abundance.
Another example of siRNA encapsulation with calcium phosphate was summa-
rized by Li
et al
. (Li
2010
). The investigators successfully showed the encapsulation
of siRNA in lipid coated calcium phosphate (LCP) nanoparticles. Calcium phosphate
core nanoparticles with siRNA are synthesized via a double reverse microemulsion
method, similar to the process employed by Morgan
et al
. with sodium citrate as the
dispersant (Morgan
2008
). The LCP nanoparticles are synthesized by mixing the
siRNA-calcium phosphate particles obtained via the microemulsion method with a
1:1 molar ratio of 1, 2-dioleoyl-3-trimethylammonium-propane chloride salt
(DOTAP)/cholesterol liposomes. The investigators demonstrated successful
in vitro
and
in vivo
gene silencing with the siRNA-LCP nanoparticles (Li
2010
). Additionally,
the investigators successfully demonstrated the use of targeted particles using 1,2-
distearoryl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-
2000) ammonium salt (DSPE-PEG)-anisamide in a nude mouse model with human
lung cancer H-460 cell xenografts with a 50% down regulation effect (Li
2010
). The
study also illustrated the effectiveness of a targeted nanoparticle delivery system over
an untargeted system.
4.2
Drug Delivery Using Calcium Phosphate Systems
Advances in drug delivery systems have the ability to: increase drug stability and
carrier capacity, incorporate both hydrophilic and hydrophobic drugs, tune carrier
properties to suit route of administration (oral, inhalation, ophthalmic, etc.), and
control drug delivery and release (prolonged release) properties. An adequate sys-
tem can not only improve the bioavailability of the drug but also reduce dosing
concentration and frequency (Adair
2010
).
Among the many desired characteristics of a nanoparticle drug delivery vehicle,
some of the most important are: protection of encapsulated therapeutic from inacti-
vation during transport, small size (10-200 nm), colloidal stability in physiological
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