Biomedical Engineering Reference
In-Depth Information
phosphate composite nanoparticles as
in vivo
drug delivery vehicles, the reported
synthetic approach yielded a range of particle sizes, most likely due to a lack of
colloidal stability for this system.
As microemulsion synthetic routes are known to produce nanoparticles with
controlled morphologies and particle sizes, a reverse microemulsion route was
utilized to encapsulate Cer
6
and Cer
10
, experimental hydrophobic therapeutic mol-
ecules, inside a calcium phosphosilicate composite nanoparticle (Kester
2008
;
Morgan
2008
). Along with the drugs, the nanoparticles were also doped with fluo-
rescein and rhodamine WT dyes, and used to illustrate simultaneous drug delivery
and imaging capabilities. An
in vitro
study demonstrated that Cer
6
-fluorescein
calcium phosphate composite nanoparticles induced 80% growth inhibition in
human vascular smooth muscle cells at a 0.2 mM ceramide concentration, which
was reported to be 25-fold less than when administering ceramide in dimethyl
sulfoxide (DMSO), while the cells exhibited no apparent morphological changes
as a result of nanoparticle cytotoxicity (Fig.
7
) (Morgan
2008
). More importantly,
in
in vitro
studies with Cer
10
-rhodamine WT calcium phosphosilicate nanoparti-
cles in UACC 903 melanoma cells it was shown that melanoma cell survival was
reduced to less than 5% at 5 mM concentrations of delivered therapeutic (Fig.
8
)
(Kester
2008
). In similar studies with Cer
10
-CPSNPs in both drug sensitive and
drug resistant breast cancer cell lines, the nanoparticle formulations exhibited
significantly greater efficacy when compared to Cer
10
-DMSO controls (Kester
2008
). Unpublished
in vivo
results for the nude mouse model did not indicate any
chronic or acute toxicity for control calcium phosphosilicate formulations. Based
Fig. 7
Effect of experimental chemotherapeutic, ceramide C6, encapsulated in calcium
phosphosilicate nanocomposite particles on cell growth.
The growth of vascular smooth mus-
cle cells is increasingly inhibited as a function of increasing hexanoyl-ceramide (Cer6) concentra-
tion delivered via calcium phosphosilicate nanoparticles (
a
) and the cells show no apparent
nanoparticle cytotoxicity induced morphology changes (
b
) (Reproduced from Morgan (
2008
).
With permission)
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