Biomedical Engineering Reference
In-Depth Information
The chapter draws attention to some of the different architectures of calcium
phosphate based systems that have been developed and focuses on calcium phos-
phate based systems that are currently being investigated in the areas of gene and
drug delivery and bioimaging. The importance of executing
in vivo
work to cor-
roborate
in vitro
results is addressed, as the fate of any delivery system is dependent
on the performance of the nanoparticulate system in the human body (best repre-
sented by
in vivo
experimentation).
2
Practical Aspects of Calcium Phosphate as a Delivery
Vehicle
2.1
Biocompatibility of Calcium Phosphate Nanoparticulates
Calcium phosphate (CP) is biocompatible and biodegradable and is therefore a suit-
able material for biomedical applications. Calcium phosphate is naturally present in
the body in bones and teeth. Additionally, both calcium and phosphate exist in the
body at millimolar concentrations while intracellular concentrations are at the
micromolar level (Oyane
2003
; Tung
1998
; Wang
2002
; Guha
2009
). As a biomin-
eral, calcium phosphate biodistributes in the body with constituent ions regulated by
the kidneys. The constituent ions of CP play essential roles in cell signaling, mem-
brane regulation, programmed cell death, synaptic transmission and general cell
functioning (Ghosh
1995
). Phosphate is primarily concentrated in the mineral phase
of bone, while smaller amounts are present as inorganic and organic compounds
(such as adenosine diphosphate (ADP) and adenosine triphosphate (ATP)) in intra-
cellular and extracellular compartments. The biocompatibility associated with cal-
cium phosphate renders it a non-toxic material system with applications in drug
delivery and imaging. The inherent non-toxicity of calcium phosphate suggests
minimal side effects due to interactions of the delivery vehicle with the body.
A calcium phosphosilicate nanoparticle (CPSNP) system has been recently
developed by Adair and co-workers. Among the innovations in the CPSNP system
relative to pure nanoscale CP is that the silicate stabilizes the amorphous calcium
phosphate (ACP) phase. Interestingly, silicon in bulk materials aids in the biomin-
eralization process (Carlisle
1988
; Dorozhkin
2010
). In the aqueous precipitation
of calcium phosphates, Eanes
et al.
, in a series of seminal papers beginning in 1965
demonstrate that an amorphous calcium phosphate phase almost immediately
forms at reasonable supersaturations, but the high solubility of the ACP drives the
dissolution-recrystallization to the more thermodynamically stable phase of
hydroxyapatite (sometimes with intermediate phase formation) (Eanes
1965,
1973
). The introduction of silicate into a solid solution of the ACP has been limited
thus far to the confined space obtained within the reverse micelle system. The
reverse micelle system used in the synthesis can be used to control the particle
diameter down to small (15-40 nm) sizes (Adair
2005, 2010
; Altınoğlu
2008, 2009,
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