Biomedical Engineering Reference
In-Depth Information
concerning possible interactions of calcium orthophosphates with
nucleic acids. Furthermore, the mechanisms of cellular uptake
and transport to the cell nucleus of calcium orthophosphate/DNA
nanodimensional complexes remain unclear either. Therefore, there
is a need to conduct a focused study on the synthesis of various forms
of nano-sized calcium orthophosphates that could elucidate the
mechanisms of binding, transport, and release of attached plasmid
DNA for understanding the gene delivery method. Research is also
warranted to understand the tracking of DNA intracellularly [638]
to understand the release and transport of DNA into cellular nuclei.
Already, some data are available that clathrin-mediated endocytosis
might be responsible for the uptake of nano-sized HA [612].
Concerning
the
healing
abilities
of
nano-sized
calcium
orthophosphates, an
inhibiting effect and even apoptotic
action of un-functionalized nano-sized HA of about 50 nm diameter
on a hepatoma cell line in the concentration range of 50-200 mg/1
was reported [652]. A similar inhibiting effect was discovered
for discrete nano-sized particles of HA, which appeared to cause
apoptosis of leukemia P388 cells [101] and rat macrophages [653].
This effect might be due to a harmful increase in the intracellular
calcium concentration. However, the correlation between the
particle dimensions and the apoptotic action of nano-sized calcium
orthophosphates appears not to be straightforward. Namely, the
apoptosis efficacy of nanodimensional particles of HA of various
sizes was found to decrease in the order of 45 > 26 > 78 > 175 nm
[654].
Hollow nano-sized spheres are extremely attractive constructions
because they can greatly enhance the load quantity. Though these
novel biomaterials can improve the total intake of drugs, they
also bring new problems, e.g
in vitro
uncontrolled release kinetics and
unreasonable metabolism pathway of the carriers [655]. In order
to solve these problems, calcium orthophosphates were selected as
suitable biomaterials to construct nanodimensional spheres hollow
inside [462, 463, 614, 656, 657]. Such spheres with dimensions
ranged from 110 to 180 nm were synthesized by an ultrasonic-
assisted wet chemical reaction in the presence of a modifier [658].
In addition, they might be prepared through emulsions [659].
Transmission electron microscopy investigations revealed that the
uniform nanodimensional spheres were formed and they were well
.
,
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