The targeting of the chemotherapeutic agents or radiosensitizer by radiation, using the liquid core

1
The targeting of the chemotherapeutic agents or
radiosensitizer by radiation, using the liquid
core microcapsules.

• Harada, Satoshi1 Ehara, Shigeru1 Ishii,
  Keizoh2 Yamazaki, Hiromichi2 Matsuyama,
  Shigeo2 Sakai, Takuro3 Obara, Yoshihiro3 Sato,
  Takahiro3 Oikawa, Masakazu3 Sera, Koichiro4
  Ito, Jun5.
• 1Iwate Medical University, School of Medicine,
  Department of Radiology
• 2Department of Quantum Science and Energy
  Engineering
• Tohoku University
• 3Takasaki Radiation Chemistry Research
  Establishment Japan Atomic Energy Research
  Institute
• 4Cyclotron Center, Iwate Medical University
• 5Nishina Memorial Cyclotron Center (NMCC), Japan
  Radioisotope Association

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Introduction

• Recent development of radiation technique made us
  possible to localize the radiation field at our
  will.
• This has been used to increase the antitumor
  effect and to decrease the adverse effect of
  radiation.
• However, we considered the another point of
  view.

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Introduction
One click anywhere to start the animation

• Consider, If there are micro-capsules, which can
  be injected intravenously or subcutenously and
  emits its contents (anticancer medicine,
  radiosensitizer, etc ) by radiation.

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Introduction
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• The Encapsulated drugs will be localized in the
  irradiated area. And the combined antitumor
  effect between the drugs and radiation is
  expected. This will lead to the better antitumor
  effect and the less adverse effect of drugs.

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Introduction

• It is known that the alginate is polymerized by
  calcium. Using that feature, we can make the
  alginate capsules by spraying the alginate into
  the solution of CaCl2.
• It is also known that the hyaluronate is
  decomposed by the irradiation and changes its
  forms.
• It is considered that the alginate capsules can
  be decomposed and emit its contents by
  irradiaton.

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AIM

• The three aims were settled in this study
• 1) Making of the hyaluronic-alginate capsule
• 2) Test whether it emit its content or not.
• 3) Test whether capsule can localize the
  encapsulated drug or not.

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Material of capsules

• 0.2 solution of alginate sodium (W/V)
• 0.02 of hyaluronic acid
• 0.2 mmol of carboplatin or Misonidazole (MISO)
• Those materials were well mixed using the pestles

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Making of capsules
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• The mixture was sprayed into the CaCl2 solution
  through the Gore Tex filter.
• The alginate was polymerized for about 5minutes.

Goretex filter
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Shape of the microcapsule
After radiation
Before radiation
Liquid core
Outer shell
The mean diameter of microcapsule was 23micro
meter. There was the round shaped liquid core in
the center of the capsule. After irradiation,
the capsule shrunk and the liquid core was
invisible.
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Imaged emission of the liquid core. (Carboplatin
by micro Particle Induced X-ray camera)
The emission of carboplatin was imaged by the
particle Induced X-ray Emission (PIXE) camera.
The microcapsule that contains carboplatin
emitted its core by radiation. The round
accumulation (click here) is microcapsule. The
scattered accumulation (click here) is the
emitted carboplatin.
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Rate of Decomposition
The percentage of the undecomposed capsules VS
time are plotted in this graph. The
decomposition of the microcapsules was completed
about three minutes after irradiation. The
significant decreases of undecomosed capsules was
observed by elevating the doses. The
microcapsule decomposed dose dependently, within
3 minutes.
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Rate of Emission (Carboplatin)
The emission rate of the carboplatin on time
courses. The emission of carboplatin was
observed only in the capsule that was irradiated.
After the rapid increases of the emission rate
by 3 minutes, the emission rate gradually
increased. The emission rate of 5 Gy or 10 Gy
was significantly greater than that of 2 Gy from
10 minutes after irradiation. However, there was
no significant differences of the emission rate
between 5 Gy and 10 Gy on each time courses.
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Antitumor effect in combination of Radiation with
encapsulated Carboplatin
The encapsulated Carboplatin had no antitumor
effect. In the irradiated microcapsule
containing carboplatin, the synergistic effect
between emitted carboplatin and radiation.
However, its antitumor effect was lower than that
of radiation with carboplatin. This is
considered the low emission of carboplatin from
the capsule.
Radiation only
Radiation Encapsulated Carboplatin
Radiation Carboplatin
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Antitumor effect in combination of Radiation with
encapsulated Misonidazole
In the combination of radiation with encapsulated
carboplatin, there were significant increases of
radiation. Its antitumor effect was lower than
that of radiation with misonidazole. However,
the misonidazole was comletely localized in the
irradiated area.
Radiation only
Radiation Encapsulated MISO
RadationMISO
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Result and Discussion.

• The Hyaluronic-Alginated microcapsule localized
  the drugs in its core within the irradiated
  field.
• There was a synergistic antitumor effect between
  radiation and emitted drugs.
• This lead to the increased antitumor effect and
  less adverse effect of drugs, which bring about
  the better cancer treatment.