Biomedical Engineering Reference
In-Depth Information
Allen
et al.
were first to study the biocompatibility of PEO
44
-
PCL
20
micelles (subscripted numerals on PEO
44
-PCL
20
represent
44 ethylene glycol, and 20 ε-caprolactone units) with PC 12 (rat
neuroendocrine tumor) and MCF-7 breast cancer cells [42]. PEO
44
-
PCL
20
micelles with a PCL block length of 2.3 kDa, showed little cell
death over a range of concentrations in the PC 12 and MCF-7 cell
lines. Yet a PEO
44
-PCL
14
micelle with a PCL block length of 1.7 kDa
induced 10-20% cell death over the same range of concentrations.
This implies that the smaller micelle (PEO
44
-PCL
14
) may have
internalized in the cell and disrupted essential metabolic functions.
In the same study,
in vitro
release of FK506 (an immunosuppressive
and neural outgrowth factor), and its synthetic analogue L-685,818
from the PEO
44
-PCL
20
micelles did not demonstrate enhanced
diff erentiation in PC 12 cells without NGF (nerve growth factor) as
was expected. Later work
in vivo
demonstrated PEO
44
-PCL
20
micelles
containing FK506 promoted a faster recovery in Hanover-Wistar rats
with crushed peripheral nerve lesions than simply injecting FK206 at
the same concentration [43]. In comparison with the indomethacin
loaded PEO-PCL micelles, the CMC of PEO
44
-PCL
20
was decreased to
10
-8
M, and thus its
in vivo
stability was increased by increasing the
length of PCL block relative to the PEO block. Dihydroxytestosterone
(DHT), another highly lipophilic small molecule, was encapsulated
with the PEO
44
-PCL
20
micelle to study its release and biological
activity [44]. Similar to the release of indomethacin, DHT released in
a Fickian manner and at a slower rate when the loaded concentration
was increased. To assess the biological activity of DHT upon release,
HeLa cells were co-transfected with MMTV-Luciferase and androgen
receptor (AR). If DHT is still biologically active when it releases
from the PEO
44
-PCL
20
micelles, then it will bind to AR and induce
transcription of the luciferase gene and ultimately the translation
of luciferase. This work demonstrated that the biological activity of
free DHT and micelles containing DHT were equivalent in terms of
luciferase expression. Therefore, the biological activity was retained
upon release in cell culture.
The hydrophobic model drugs discussed until now utilized dialysis
to remove free drug. This typically works for most model drugs and
PEO-PCL micelles, however in the case of fenofibrate approximately
75% of the initially loaded model released during dialysis [22]. This
can be overcome by loading polymer and fenofibrate in ACN, and
approaching the azeotrope of water-ACN through the addition of
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