Biomedical Engineering Reference
In-Depth Information
conditions, non-toxicity, and targetability to specific tissues in the body (Adair
2010
). Such drug delivery vehicles are especially desirable in chemotherapy, since
various barriers are encountered at the cellular and tumor levels as well as
en route
to the diseased tissue when trying to deliver a chemotherapeutic substance (Serpe
2006
). Calcium phosphate nanoparticles have not been studied in drug delivery as
extensively as in gene delivery applications, but studies thus far have demonstrated
the potential efficacy of these nanoparticles as drug delivery vehicles. Most impor-
tantly, improvements in synthetic approaches for calcium phosphate and calcium
phosphosilicate nanoparticles have allowed researchers to develop delivery carriers
which meet the desired criteria for an efficacious drug delivery system. This is
especially promising for
in vivo
drug delivery applications, where, for example, the
protection of encapsulants from inactivation is vital since delivery of therapeutics
adsorbed to the nanoparticle surface may suffer from some of the same drawbacks
as conventional drug delivery approaches (Adair
2010
).
In vitro
and
in vivo
drug delivery studies with calcium phosphate based com-
posite nanoparticle systems have included delivery of insulin, cisplatin, metho-
trexate, 7-hydroxy-2-dipropyl-aminotetralin (7-OH-DPAT), hexanoyl-ceramide
(Cer
6
) and decanoyl-ceramide (Cer
10
) (Barroug
2002, 2004
; Chu
2002
; Kester
2008
; Morgan
2008
; Mukesh
2009
; Ramachandran
2009
). Most of these studies
have fallen short in demonstrating the desired characteristics of a drug delivery
vehicle for calcium phosphate nanoparticles, especially in terms of size and col-
loidal stability. Furthermore, most studies have focused on using calcium phosphate
nanoparticles where the drug entity is adsorbed to the surface (i.e., surface decora-
tion) rather than protected within the interior of the nanoparticle via encapsulation.
The most recent study on insulin focused on demonstrating the use of calcium
phosphate nanocomposites with enteric coatings for oral delivery as a way to over-
come the drawbacks of traditional delivery via subcutaneous injections. Calcium
phosphate nanoparticles were coated with PEG and Eudragit 100 copolymer, and
in vitro
delivery of insulin was assessed over time in phosphate buffered saline
(PBS) solution (Ramachandran
2009
). The nanoparticles did not exhibit cytotox-
icity as confirmed via an
in vitro
MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyltetrazolium bromide) assay and the released insulin molecules maintained
the same size and conformation as before delivery (Ramachandran
2009
).
Cytotoxicity and release studies were also conducted with apatite nanoparticles
containing the chemotherapeutic cisplatin, where drug induced cytotoxicity was
assessed in K8 mouse osteosarcoma cells (Barroug
2002, 2004
). However, these
studies were limited to
in vitro
delivery, falling short of demonstrating
in vivo
efficacy. Similarly, the chemotherapeutic drug methotrexate was loaded into the
surfaces of calcium phosphate nanoparticles, where the drug was both an encap-
sulant and the dispersing agent. The nanoparticles did not exhibit long term col-
loidal stability, as shown by measured particle size increase over a period of
90 days at 2-8°C and room temperature (Mukesh
2009
). The ocular hypotensive
agent 7-OH-DPAT in a calcium phosphate nanoparticle formulation was tested
in vivo
in rabbits, and exhibited improved efficacy when compared to the free
7-OH-DPAT (Chu
2002
). While this drug study demonstrated potential for calcium
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