Journal
JOURNAL OF CONTROLLED RELEASE
Volume 167, Issue 3, Pages 315-321Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2013.02.016
Keywords
Photodynamic therapy; Graft copolymer; Non-covalent complex; EPR effect
Funding
- Japan Society for the Promotion of Science (JSPS) [20500410, 24510300, 23240074]
- Ministry of Education, Culture, Science, Sports and Technology of Japan (MEXT) [2306]
- Grants-in-Aid for Scientific Research [20500410, 24510300, 23240074] Funding Source: KAKEN
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Photofrin (R) (porfimer sodium) is a photosensitive reagent used for photodynamic therapy (PDT) of tumors and dysplasias. Because only photo-irradiated sites are damaged, PDT is less invasive than systemic treatments. However, a photosensitive reaction is a major side effect of systemically delivered Photofrin. To enhance localization of Photofrin to tumors, we have formulated Photofrin with the tumor-localizing graft copolymer poly(ethylene glycol)-grafted poly(L-lysine), PLL-g-PEG. We demonstrate that Photofrin preferentially interacts with PLL-g-PEG through both ionic and hydrophobic interactions. The serum competitive study showed that the highly PEG-grafted PLL is better for preventing serum binding to the Photofrin/PLL-g-PEG complex. In tumor-bearing mice, formulation of Photofrin with PLL-g-PEG enhanced tumor localization of Photofrin as twice as Photofrin alone and concomitantly suppressed the photosensitivity reaction drastically. (C) 2013 Elsevier B. V. All rights reserved.
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