Biomedical Engineering Reference
In-Depth Information
efficacy for the surface decoration scheme. Unfortunately, a preliminary evaluation
of a nanoparticle drug or bioimaging scheme limited to just
in vitro
studies can
lead to a false sense of efficacy when, in fact, there is no efficacy for the critical
in vivo
tests that actually verify the true value of a nanoparticle system for eventual
human health care.
3.1
Crystalline Calcium Phosphate
The most thermodynamically stable and widely used form of calcium phosphate is
the crystalline phase of hydroxyapatite. As a function of time, the amorphous cal-
cium phosphate phase will eventually transform into hydroxyapatite unless mea-
sures (such as doping) are taken to inhibit transformation (Dorozhkin
2010
). Some
examples of inhibitory agents are citrate (Lopez-Macipe
1999
; Brecevic
1979
;
Johnsson
1991
), phosphocitrate (Johnsson
1991
), silicate (Skrtic
2002
; Morgan
2008
; Kester
2008
; Altınoğlu
2008
; Muddana
2009
; Barth
2010
; Altınoğlu
2010a
)
and casein phosphopeptides (Cross
2004
). Various researchers have studied the ben-
efits of the crystalline structure of calcium phosphate primarily for drug treatments
involving bone diseases but also for other drug delivery and imaging systems.
Synthetic schemes for crystalline particles range from the simple precipitation
of calcium and phosphate based on solutions such as (NH
4
)
2
HPO
4
and Ca(NO
3
)
2
H
2
O with an aqueous solution of the dopant (Mondejar
2007
) to polymeric micelle
templated systems (Ye
2010
) and reverse-microemulsion systems (Mukesh
2009
).
In terms of dispersion, for the nanoparticulate systems, the drug being delivered
is the dispersant of choice for some investigators (Palazzo
2007
; Kunieda
1993
;
Immamura
1995
). Other dispersants include DNA (Mondejar
2007
) and cholesterol-
bearing mannan (CHM) (Yamane
2009
) while no dispersant is evident in some
systems (Mukesh
2009
).
Crystalline calcium phosphate or hydroxyapatite (HA) has been studied as both
a drug and gene delivery system (Barroug
2002, 2004
; Ye
2010
; Sokolova
2007b
).
Hollow hydroxyapatite nanospheres and nanotubes have been explored as carriers
for the drug vancomycin (Ye
2010
). The hollow nature of the calcium phosphate
nanoparticles has the potential for higher drug loading capacity as compared to
solid particles. Crystalline nanoparticles have also been investigated for their use in
gene delivery (Sokolova
2006a,b, 2007a,b, 2010
). The delivery vehicle model
employed by Sokolova and colleagues uses the surface decoration approach and the
combined surface decoration-encapsulation models. While
in vitro
work performed
using their particles offer promising results, an
in vivo
model to better understand
the performance of the particles in a dynamic, protein-abundant setting is lacking
and should be the focus of future studies.
For bioimaging, it has been suggested that crystalline calcium phosphate has the
ability to improve fluorescence properties when doped with lanthanide ions by
preventing quenching (Mondejar
2007
). Dynamic quenching (or quenching), a non-
radiative relaxation mechanism occurs when one fluorescent molecule or ion
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