Biomedical Engineering Reference
In-Depth Information
the IC50 of free cucurbitacin in methanol was approximately half of
the IC50 of cucurbitacin released from PEO-PCL micelles. However,
there was no statistical diff erence in terms of in vivo tumor volume
upon treatment with free and PEO-PCL encapsulated cucurbitacin I
as both virtually abolished growth. If a targeting moiety to the tumor
(e.g., EGF [57], Her2/neu [58], PSMA [59]) was desired to cover the
micelle and enhance in vivo activity, the micelle size may need to be
reduced.
Additives may be used to improve encapsulation efficiency and
potentially the release of the drug from the core while maintaining
in vivo activity. Rapamycin, an inhibitor of cell proliferation in solid
tumors, has been efficiently encapsulated into PEO-PCL micelle cores
with the coaddition of α-tocopherol (Vitamin E) [60]. In this study,
a series of PEO-PCL micelles with a constant PEO block length of 5
kDa and varying PCL block lengths of 6, 10, and 18 kDa were used to
encapsulate and release rapamycin. α-Tocopherol is more lipophilic
than a single unit of caprolactone, and will partition into the PCL
core and provide greater thermodynamic affinity of rapamycin for
the core; rapamycin is extremely lipophilic with an octanol-water
partition coefficient of 5.8. As expected, the CMC of these micelles
decreased with increasing PCL block length and were on the order
of 10 -7 -10 -8 M. The addition of α-tocopherol in molar ratio of 1:10
and 1:20 to PEO-PCL demonstrated negligible increases in the CMC.
However, addition of α-tocopherol beyond the ratio of 1:20 shifted
the phase equilibria of the PEO-PCL-water system to precipitate
as particles greater than 400 nm. Encapsulation efficiencies were
increased with 1:20 molar ratios of α-tocopherol in each PEO-PCL
micelle, with an apparent optimum PCL block length of 10 kDa
resulting in 72% efficiency. The PEO-PCL micelles with 18 kDa
PCL blocks encapsulated only 66%. As the reduction in efficiency
compared with the 10 kDa block was unexpected, it foreshadowed
precipitation in release studies. Thus the addition of rapamycin
to PEO-PCL micelles loaded with α-tocopherol further shifted the
phase equilibria of the PEO-PCL-water system to precipitate as
seen with higher molar ratios (>1:20 α-tocopherol). The release of
rapamycin in saline was not significantly impacted by α -tocopherol.
However, in 4% BSA, α-tocopherol greatly improved the sustained
release characteristics. This may be due to the improved affinity of
rapamycin for the α-tocopherol-rich micelle core compared with
BSA. In some cases, the addition of hydrophobic additives may not
 
Search WWH ::




Custom Search