Biomedical Engineering Reference
In-Depth Information
A representative copolymer for improving the solubility of hydrophobic
drugs in aqueous media is poly(2-methacryloyloxyethyl phosphorylcholine-co-
n-butyl methacrylate) (PMB).
38-40
Wada et al.
41
prepared PMB with 70 mol%
of the BMA unit (PMB30W) to solubilize paclitaxel (PTX) over 1000 times.
The diameter of the PMB aggregate containing 1 mg mL
21
of PTX (PTX-
PMB30W) was 50 nm in aqueous medium. Antitumor efficacies of PTX-
PMB30W and PTX dissolved in polyoxyethylated caster oil were similar,
following weekly intraperitoneal administration of 50 mg kg
21
PTX in nude
mice transplanted with MX-1 cells. However, after the dose was increased to
200 mg kg
21
PTX, all animals receiving the PTX-PBM30W survived, whereas
all animals died within 1 minute after being injected with the same dose of
PTX (Figure 10.1). This result demonstrates that MPC-protected nano-
delivery vehicles (NDVs) could lower the immediate toxicity after injection.
Furthermore, small hydrophobic drugs incorporated into block copolymer
micelles can be much better protected from the bulk phase than those taken up
by random copolymer aggregates. The studies by Yusa et al. showed that the
water solubility of PTX can be enhanced dramatically by use of an aqueous
micelle solution of PMB, which demonstrated that block copolymers are much
more effective for enhancing solubility because of their associative structure in
aqueous media.
42
Chu et al.
43
prepared PTX-loaded PMB micelles and
investigated the micelles' morphology as well as the in vitro drug release
kinetics. The TEM studies indicated a small size (less than 30 nm), a narrow
size distribution, and a regularly spherical shape for the drug-loaded micelles.
An in vitro release study showed that the release rate of PTX from the
polymeric micelles was slow and sustained. Kano et al. demonstrated
enhancement of the solubilization of miconazole (MCZ), vidarabine (Ara-
d
n
4
y
3
n
g
|
7
Figure 10.1
(a) Chemical structure of poly(MPC-co-n-butyl methacrylate) (PMB).
(Reproduced from Goda et al.
38
with permission from Elsevier.) (b)
Growth inhibition of tumor xenografts on day 16. The antitumor
efficacy of PTX-PMB30W at 200 mg kg
21
PTX was significantly higher
than that of PTX-PMB30W at 50 mg kg
21
PTX. (Reproduced from
Kano et al.
41
with permission from The International Institute of
Anticancer Research.)
