Biomedical Engineering Reference
In-Depth Information
micelles, the amount precipitated nearly doubled compared with
micelles loaded with 2 mg of AMI. PEO-PCL (13 kDa) micelles with
2 mg AMI induced 90% less hemolysis compared with equivalent
free AMI over a two order magnitude concentration range. When
this same micelle was loaded to 5 mg AMI, the extent of hemolysis
was equivalent to free AMI. Thus, both the amount of drug loaded
and the PCL block length should be optimized in preformulation of
prospective drug candidates.
3.2.1
Drug Delivery of Anti-Cancer Agents from Diblock
PEO-PCL Micelles
Since PEO-PCL micelles can protect from some unwanted drug
side eff ects, it is useful to understand how they deliver cytotoxic,
hydrophobic drugs often used in chemotherapy. One of the most
widely used chemotherapeutic agents is doxorubicin (DOX), an
anthracyline antibiotic that induces apoptosis in tumor-specific
cells [46-49]. A series of PEO-PCL polymers were synthesized
with varying PCL block lengths (2-24.7 kDa) to investigate the
cytotoxicity of these micelles and their ability to load and release
DOX [25]. Varying the PCL core length did not increase the loading
capacity as seen with other model drugs, maximizing at 3-4%
w/w DOX. However, no detectable hemolysis was induced at
concentrations as high as 200 μg/mL DOX in PEO-PCL (5 and 24.7
kDa), compared with 11% hemolysis at the same concentration for
free DOX. Dynamic light scattering showed substantial increases
in polymer size with increases in PCL block length (22-100 nm in
diameter). At pH 7.4, DOX was cumulatively released slightly faster
(~15%) with a 24.7 kDa PCL block compared with a 5 kDa (~10%)
over 35 days. At pH 5, the cumulative release was accelerated to 80%
in the 24.7 kDa block, and to 60% in the 5 kDa block over the same
time frame as pH 7.4. Slightly acidic conditions may have increased
the rate of ester degradation in the core. However, it is more likely
that the increase in release rate is due to the lowered octanol-water
partition coefficient at reduced pHs (the Log Po/w of DOX is 5.1 at
pH 7.4 and 0.2 at pH 5) [50]. The fact that the larger block length
accelerated release at both pHs, suggests that the PCL core viscosity
was reduced, potentially due to an increased volume of core. This
unexpected release behavior will be analyzed further with respect to
thermodynamic affinity. It is important to notice the increased rate
Search WWH ::
Custom Search