Biomedical Engineering Reference
In-Depth Information
an increase in fluorescence signal at the site of injection after 1 h.
These results suggest that subcutaneous and intramuscular injection
provide a means for micelles to simply solubilize a drug and then be
site-injected to a target organ or a solid tumor that is inoperable.
Alternatively, if blanket coverage of the circulatory system needs
to be to be treated as is the case in metastatic cancers, intravenous
injection of the micelles would be the preferred route. Conjugated
fluorescence dyes to PEO-PCL micelles
in vitro
and
in vivo
will play an
important role in pre-clinical evaluation of micelle delivered drugs.
Although stability of the micelles
in vivo
is an important factor
to consider, sometimes micelles need to protect the drug from
degradation. This is the case with curcumin, a anti-cancer agent
known to down regulate genes associated with angiogenesis of
tumors [83]. PEO-PCL micelles with a PEO block length of 5 kDa and
PCL with a block length of 13 kDa were used to deliver curcumin
to investigate the pharmacokinetics in Sprague-Dawley rats [84]. In
this study, the micelle formulation of curcumin was compared with
a solubilized formulation employing dimethylacetamide, PEG 400,
and isotonic dextran. High-performance liquid chromatography
(HPLC) was used to analyze curcumin in plasma. Since curcumin is
rapidly hydrolytically degraded, the soluble formulation had a half-
life of only 0.5 h, while the PEO-PCL formulation increased this half-
life approximately 120-fold. After 2 h, HPLC wasn't able to detect
curcumin from the soluble formulation, whereas curcumin from the
PEO-PCL micelle formulation was detectable for 2 days. Not only did
the PEO-PCL micelles protect curcumin from degradation, it also
increased the solubility several orders of magnitude.
Another anticancer agent, 10-hydroxycamptothecin (HCPT),
is a powerful antitumor drug against lung, ovarian, breast, and
stomach cancers. Yet it is limited therapeutically due to its poor
water solubility and a short half-life
in vivo
. PEO-PCL micelles were
used to encapsulate HCPT and were injected into Wistar rats and
S
180
tumor bearing mice to evaluate the pharmacokinetics and tissue
distribution [73]. A series of PEO-PCL micelles with variations in the
hydrophilic PEO block length and lipophilic PCL block length were
shown to have CMC's on the order of 10
-7
-10
-8
M. Radiolabeled
125
I-HCPT had greater tumor specificity and increased half-life in
micelles with PEO block lengths of 10 kDa, compared with 2 or 5
kDa PEO blocks. Thus not only should the PCL block be optimized in
preclinical studies, but so should the PEO block.
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