Calcium Phosphate and Calcium Phosphosilicate Mediated Drug Delivery and Imaging - Intracellular Delivery: Fundamentals and Applications - page 727

interacts with another fluorescent molecule or ion (due to proximity or interactions).
The incorporation of lanthanide ions into apatites via substitution of the calcium
ions in the crystallographic lattice sites is expected to overcome the problem of
quenching. The incorporation of the lanthanide ions in the appropriate lattice sites
serve as fluorescent centers that act to reduce quenching, as stringent ion placement
prevents interaction with other fluorescent ions.
A limitation, as suggested by Mondejar et al ., is that crystalline calcium phos-
phate usually results in larger particle sizes (due to the need for a highly crystalline
structure), sometimes too large for cellular uptake. Poor size control due to the
synthetic method also leads to larger particles and as explained earlier, increased
susceptibility for RES and MPS mediated removal under in vivo conditions.
Hydroxyapatite bulk implants, however, are exceptionally useful for implant treat-
ment options (Nelson 2006 ) where cell uptake is irrelevant and HA exists in the
form of large blocks of material. For imaging and drug delivery however, the size
of particles can pose a problem and alternative structures or composite structures
are sometimes preferred and are currently being developed as options to crystalline
CP particles.

3.2 Polymeric - Calcium Phosphate Systems

Hybrid nanoparticles composed of calcium phosphate and polymeric materials are
synthesized using polymer cross-linked micelles and hollow nanocages (Perkin
2005 ), nanogels (Sugawara 2006 ) and triblock copolymers (Cao 2010 ). In addition,
block copolymer templates (though not incorporated in the actual particle) are used
to synthesize hollow calcium phosphate nanoparticles (Tjandra 2006 ). The advan-
tage of combined polymer-calcium phosphate systems is the higher loading poten-
tial of dyes (Klesing 2010 ) or drugs (Cao 2010 ) due to further loading ability in the
polymer layer in addition to loading in the calcium phosphate component, and the
ability to load hydrophobic drugs into the polymer layer.
Polymeric-calcium phosphate systems that are currently under investigation
employ a variety of synthetic schemes. The cross-linked micelle and nanocage
approach employed by Perkin et al . yields polymer core-amorphous calcium phos-
phate shell micelle particles and hollow calcium phosphate nanocages on the order
of 50-70 nm in diameter. Both types of particles are assayed for the permeability
of b-carotene as a function of calcium phosphate mineralization with optimal
results for the unmineralized particles (Perkin 2005 ). The particles demonstrate
potential applications as pH-responsive nanostructures for use in bioimaging and
therapeutic delivery (Perkin 2005 ).
Hybrid polymer-calcium phosphate nanoparticles are synthesized by the pre-
cipitation of calcium phosphate in the presence of cholesterol-bearing pullalan
(CHP) nanogels by the pH-gradient method (based on the pH dependent solubility
of calcium phosphate) (Sugawara 2006 ). The assumed architecture of the hybrid
particles are a composite CHP-calcium phosphate particle. The investigators report