Polyethylene Glycol Polyester Block Copolymers: Biocompatible Carriers for Nanoparticulate Drug Delivery - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 64

et al. also saw DOX with PEO-PCL micelles localized to the cytoplasm,
as opposed to free DOX localized in the nucleus [25]. Cisplatin,
another anti-cancer agent was encapsulated with 73% efficiency into
PEO-PCL micelles and was taken up into SKOV-3 ovarian cancer cells
[72]. However its localization to endocytic vesicles in the cytoplasm
retarded its potential cytotoxicity compared with pH-sensitive
micelles localizing the drug in the nucleus. Thus PEO-PCL micelles
are endocytosed into a variety of cell lines, and typically localize in
endocytic vesicles in the cytoplasm. Although the majority of the
drug is likely be released independent of cellular internalization, if
the drug requires localization in the nucleus, there may be reduced
efficacy in vivo .

3.3.3 Efficacy and Stability of PEO-PCL Micelle Drug

Delivery in vivo

Micelles of PEO-PCL have demonstrated sustained release, improved
solubilization, and good efficacy in vitro . Lavasanifar and coworkers
examined the pharmacokinetics and biodistribution of CsA released
from PEO-PCL micelles in Sprague-Dawley rats compared with the
current formulation in Cremophor ® EL [79]. The PEO-PCL micelles with
PCL block lengths of 5 and 13 kDa both encapsulated approximately
30% of the drug and were nominally 100 nm in saline. These micelles
increased both the blood and plasma CsA concentrations approximately
6-fold and reduced the volume of distribution and clearance 10- and
8-fold, respectively. The pharmacokinetics of these micelles imposed
lower concentration distributions of CsA in all organs except the heart.
Most paramount, the PEO-PCL micelles reduced the concentration in
the kidneys, the primary site of toxicity.
Rapamycins pharmacokinetics and tissue distribution in rats was
investigated upon release from PEO-PCL micelles with and without
α-tocopherol, compared with the current solution formulation of
Tween 80/PEO400/ N , N dimethylacetamide [80]. The blood and
plasma concentrations were not significantly increased with the PEO-
PCL micelles with or without α-tocopherol. However, the micelles with
α-tocopherol had a reduced volume of distribution and clearance.
Additionally, the organ distribution of rapamycin was significantly
reduced in PEO-PCL micelles with α-tocopherol liver, kidney,
spleen, brain, lung, and heart. PEO-PCL micelles optimally reduced
rapamycin distribution compared with micelles with α-tocopherol