Targeted delivery of chemotherapeutic agents using improved radiosensitive liquid core microcapsules and assessment of their antitumor effect.
OBJECTIVE
Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy.


METHODS
We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 microg) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl(2) solution supplemented with 0-0.01% yttrium. These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy (60)Co gamma-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma.


RESULTS
Microcapsules that had been polymerized using a 4.34% CaCl(2) solution supplemented with 5.0 x 10(-3)% (10(-3)% meant or 10%(-3)) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects.


CONCLUSIONS
The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.
Harada
Satoshi
S
Department of Radiology, Iwate Medical University, Morioka, Japan. sharada@iwate-med.ac.jp
Ehara
Shigeru
S
Ishii
Keizo
K
Yamazaki
Hiromichi
H
Matsuyama
Shigeo
S
Sato
Takahiro
T
Oikawa
Shyoichi
S
Kamiya
Tomihiro
T
Arakawa
Kazuo
K
Yokota
Wataru
W
Sera
Koichiro
K
Ito
Jyun
J
D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry; D002118:Calcium / Q000032:analysis; D002122:Calcium Chloride / Q000032:analysis / Q000737:chemistry; D002214:Capsules / Q000009:adverse effects / Q000138:chemical synthesis / Q000528:radiation effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry; D003037:Cobalt Radioisotopes / Q000494:pharmacology; D003124:Colorimetry / Q000379:methods; D003131:Combined Modality Therapy / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D005354:Fibrosarcoma / Q000139:chemically induced / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D010984:Platinum / Q000032:analysis; D011108:Polymers; D013997:Time Factors; D015019:Yttrium / Q000008:administration & dosage / Q000494:pharmacology
D000464:Alginates; D000970:Antineoplastic Agents; D002214:Capsules; D003037:Cobalt Radioisotopes; D006603:Hexuronic Acids; D011108:Polymers; D010984:Platinum; D015019:Yttrium; D020723:Glucuronic Acid; D006820:Hyaluronic Acid; D016190:Carboplatin; D002122:Calcium Chloride; D002118:Calcium