The DOI matches its Crossref record; 98 of the 98 references it cites were found in a registry or an index.
Vascular permeability in cancer and infection as related to macromolecular drug delivery, with emphasis on the EPR effect for tumor-selective drug targeting
Open accessAbstract
Tumor and inflammation have many common features. One hallmark of both is enhanced vascular permeability, which is mediated by various factors including bradykinin, nitric oxide (NO), peroxynitrite, prostaglandins etc. A unique characteristic of tumors, however, is defective vascular anatomy. The enhanced vascular permeability in tumors is also distinctive in that extravasated macromolecules are not readily cleared. We utilized the enhanced permeability and retention (EPR) effect of tumors for tumor selective delivery of macromolecular drugs. Consequently, such drugs, nanoparticles or lipid particles, when injected intravenously, selectively accumulate in tumor tissues and remain there for long periods. The EPR effect of tumor tissue is frequently inhomogeneous and the heterogeneity of the EPR effect may reduce the tumor delivery of macromolecular drugs. Therefore, we developed methods to augment the EPR effect without inducing adverse effects for instance raising the systemic blood pressure by infusing angiotensin II during arterial injection of SMANCS/Lipiodol. This method was validated in clinical setting. Further, benefits of utilization of NO-releasing agent such as nitroglycerin or angiotensin-converting enzyme (ACE) inhibitors were demonstrated. The EPR effect is thus now widely accepted as the most basic mechanism for tumor-selective targeting of macromolecular drugs, or so-called nanomedicine.
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Cites
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Self-citationTumor vascular permeability and the EPR effect in macromolecular therapeutics: a review
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Cited by
Maeda, H., Nakamura, H., & Fang, J. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.10.002 · Cited by 2,376
Self-citationMaeda, H. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.01.002 · Cited by 1,179
Self-citationKobayashi, H., Watanabe, R., & Choyke, P. L. (2014) · Theranostics · doi:10.7150/thno.7193 · Cited by 996
Kalyane, D., Raval, N., Maheshwari, R., Tambe, V., Kalia, K., & Tekade, R. K. (2019) · Materials Science and Engineering: C · doi:10.1016/j.msec.2019.01.066 · Cited by 849
Fang, J., Islam, W., & Maeda, H. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.005 · Cited by 757
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Metadata
- Authors
- MAEDA, H.
- Venue
- Proceedings of the Japan Academy, Series B
- Publisher
- Japan Academy
- Published
- 2012
- Volume
- 88
- Issue
- 3
- Pages
- 53-71
- ISSN
- 0386-2208 (ISSN-L)
- 1349-2896
- OpenAlex
- W1981147276
- Cited by
- 291
- References
- 98
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- bronze
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- MAEDA, H. (2012). Vascular permeability in cancer and infection as related to macromolecular drug delivery, with emphasis on the EPR effect for tumor-selective drug targeting. Proceedings of the Japan Academy, Series B. https://doi.org/10.2183/pjab.88.53
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