| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-08-07 |
| タイトル |
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タイトル |
Delivery of aPD-L1 antibody to i.p. tumors via direct penetration by i.p. route: Beyond EPR effect. |
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言語 |
en |
| 言語 |
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|
言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Mayu Yamamoto
Taiki Kurino
Reiko Matsuda
Haleigh Sakura Jones
Yoshito Nakamura
Taisei Kanamori
Atushi B Tsuji
Aya Sugyo
Ryota Tsuda
Yui Matsumoto
Yu Sakurai
Hiroyuki Suzuki
Kensuke Osada
Tomoya Uehara
Yukimoto Ishii
Hidetaka Akita
Yasushi Arano
Akihiro Hisaka
Hiroto Hatakeyama
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Chemotherapy for peritoneal dissemination is poorly effective owing to limited drug transfer from the blood to the intraperitoneal (i.p.) compartment after intravenous (i.v.) administration. i.p. chemotherapy has been investigated to improve drug delivery to tumors; however, the efficacy continues to be debated. As anticancer drugs have low molecular weight and are rapidly excreted through the peritoneal blood vessels, maintaining the i.p. concentration as high as expected is a challenge. In this study, we examined whether i.p. administration is an efficient route of administration of high-molecular-weight immune checkpoint inhibitors (ICIs) for the treatment of peritoneal dissemination using a model of peritoneal disseminated carcinoma. After i.p. administration, the amount of anti-PD-L1 antibody transferred into i.p. tumors increased by approximately eight folds compared to that after i.v. administration. Intratumoral distribution analysis revealed that anti-PD-L1 antibodies were delivered directly from the i.p. space to the surface of tumor tissue, and that they deeply penetrated the tumor tissues after i.p. administration; in contrast, after i.v. administration, anti-PD-L1 antibodies were only distributed around blood vessels in tumor tissues via the enhanced permeability and retention (EPR) effect. Owing to the enhanced delivery, the therapeutic efficacy of anti-PD-L1 antibody in the peritoneal dissemination models was also improved after i.p. administration compared to that after i.v. administration. This is the first study to clearly demonstrate an EPR-independent delivery of ICIs to i.p. tumors by which ICIs were delivered in a massive amount to the tumor tissue via direct penetration after i.p. administration. |
| 書誌情報 |
Journal of controlled release : official journal of the Controlled Release Society
巻 352,
p. 328-337,
発行日 2022-10
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| 出版者 |
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出版者 |
Elsevier |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0168-3659 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
36280153 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1016/j.jconrel.2022.10.032 |
