JAEA-Review-2010-065.pdf:15.99MB - 日本原子力研究開発機構

3-59
Improvement of Microcapsules that Reslease Core
Contents via Radiation
S. Harada a) , S. Ehara, a) K. Ishii b) , T. Sato c) , S. Yamazaki b) ,
N. Matsuyama b) and T. Kamiya c)
a) Department of Radiology, Iwate Medical University,
b) Department of Quantum Science and Energy Engineering, Tohoku University,
c) Department of Advanced Radiation Technology, TARRI, JAEA
Introduction
Since 2005, we have been developing microcapsules
that release anticancer drugs during radiotherapy and
anticancer drug targeting 1), 2) . The irradiated microcapsules
release anticancer drugs. The released anticancer drugs
along with radiation synergistically act against the tumor,
resulting in increased antitumor activity. Localization of
anticancer drugs by using microcapsules decreases the
adverse effects of these drugs.
Previously, these microcapsules were generated by
polymerizing hyaluronic acid and alginate with Ca 2+ and
Fe 2+ ions. The mechanism of anticancer drug release by
the microcapsules was as follows: radiation-induced (1)
decomposition of hyaluronic acid and (2) destruction of
Fe 2+ in the polymer by conversion of Fe 2+ into Fe 3+ .
However, the frequency of anticancer drug release was low,
i.e., 72.3 ± 2.3%, at 20-Gy radiation dose.
It is known that radiation-induced breakdown of H 2O 2
releases oxygen through the following chemical reaction:
2H 2O 2 → O 2 + 2H 2O. If H 2O 2 is added to the
microcapsules, radiation-induced release of oxygen may
increase the pressure within the capsules and thus result in
increased rupturing of the microcapsules. In this study,
we tested whether addition of H 2O 2 increased the
radiation-induced rupturing of microcapsules.
Materials and Methods
The capsules were generated by spraying a mixture of
3.0% hyaluronic acid and 2.0% alginate, supplemented
with 0.3% H 2O 2, 0.2 mmol of carboplatin, and 0.5 mol/L
each of FeCl 2 and CaCl 2. One million microcapsules were
allowed to float in normal saline; thereafter, the capsules
were irradiated with 60 Co γ ray at doses ranging from 0.5 to
3 Gy with 0.5 Gy interval at Iwate Medical University.
The radiation-induced rupturing of the microcapsules was
imaged using a micro PIXE camera in TIARA.
Results
The micro-PIXE image of microcapsules by Pt signals is
shown in Fig. 1 and the frequency of radiation-induced
rupturing is also shown in Fig. 2.
Before irradiation, the contours of microcapsules were
round and their liquid core was distinct (Fig. 1A). After
irradiation, the contours of microcapsules were made
irregular and the releasing of liquid core as carboplatin
could be observed (Fig. 1B).
JAEA-Review 2010-065
- 115 -
The frequency of rupturing of the microcapsules
increased with increase in the radiation dose (Fig. 2). The
frequencies of rupturing of the microcapsules with H 2O 2
added was significantly increased than those of without
H 2O 2 added when radiation doses was greater than 2 Gy
(Fig. 2).
0
5
10
15
20
25
30
Fig. 1 Rupturing of microcapsules observed by micro
PIXE camera. A: Before irradiation, B: After
irradiation.
Percent of decomposition
90
80
70
60
50
40
30
20
10
A
A B
row
0 5 10 15
col
20 25 30
0.50 0.75 1.00 1.25 1.50
MM46MC30Gy1_1_4Pt_sm_rs_md
Fig. 2 Micro-PIXE images of the ruptured
microcapsules by micro PIXE camera. A and the
frequency of rupturing of microcapsules. (■) with
H2O 2 added, (◆) without H 2O 2 added.
Discussion
In the conventional radiotherapy, 2-Gy fractions of
radiation were administered. According to our data,
addition of H 2O 2 significantly increased the rupturing of
microcapsules at radiation doses 2 Gy, compared with that
of no addition of H 2O 2. Addition of H 2O 2 to the
microcapsules is considered to be useful for their clinical
application.
References
1) S. Harada et al., TIARA Ann. Rep. 2003 (2004) 276.
2) S. Harada et al., Nucl. Instrum. Meth. B 260 (1) (2007)
16.
row
B
0
0 1 2 3
Radiation Dose (Gy)
0
25
50
75
100
125
0 25 50 75 100 125
col
0.000.0250.050.0750.100.1250.150.1750.200
MM46MC30Gy5_1_2Pt_sm_rs_md