The use of PVP as a polymeric carrier to improve the plasma half-life of drugs

Kaneda, Yoshihisa; Tsutsumi, Yasuo; Yoshioka, Yasuo; Kamada, Haruhiko; Yamamoto, Yoko; Kodaira, Hiroshi; Tsunoda, Shin-ichi; Okamoto, Takayuki; Mukai, Yohei; Shibata, Hiroko; Nakagawa, Shinsaku; Mayumi, Tadanori

doi:10.1016/j.biomaterials.2003.10.003

Cited by 181 publications

(130 citation statements)

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“…The Ce6 molecule has been adapted to improve its clinical efficacy, and has decreased side effects compared to first generation photosensitizers from hematoporphyrin derivatives. Photolon™/Fotolon™ is a water-soluble photosensitizer; the conjugation of Ce6 to the hydrophilic polymer polyvinylpyrrolidone (PVP) making Photolon hydrophilic in nature (6)(7)(8)(9). While lipophilic photosensitisers (e.g, lipophilic porphyrins) are preferentially taken up through the plasma membrane of the cell, hydrophilic photosensitisers tend to be taken up by pinocytosis (10), a form of endocytosis, where particles are taken in by the cell in endosomal vesicles which subsequently fuse with lysosomes (i.e., lysosomotropic delivery) to exerts its effects.…”

Section: Introductionmentioning

confidence: 99%

Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes

Olivo

2011

Int J Oncol

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Abstract. The localization of photosensitizers in the subcellular compartments during photodynamic therapy (PDT) plays a major role in the cell destruction; therefore, the aim of this study was to investigate the intracellular localization of Chlorin e6-PVP (Photolon™) in malignant and normal cells. Our study involves the characterization of the structural determinants of subcellular localization of Photolon, and how subcellular localization affects the selective toxicity of Photolon towards tumor cells. Using confocal laser scanning microscopy (CLSM) and fluorescent organelle probes; we examined the subcellular localization of Photolon™ in the murine colon carcinoma CT-26 and normal fibroblast (NHLC) cells. Our results demonstrated that after 30 min of incubation, the distribution of Photolon was localized mainly in the cytoplasmic organelles including the mitochondria, lysosomes, Golgi apparatus, around the nuclear envelope and also in the nucleus but not in the endoplasmic reticulum whereas in NHLC cells, Photolon was found to be localized minimally only in the nucleus not in other organelles studied. The relationship between subcellular localization of Photolon and PDT-induced apoptosis was investigated. Apoptotic cell death was judged by the formation of known apoptotic hallmarks including, the phosphatidylserine externalization (PS), PARP cleavage, a substrate for caspase-3 and the formation of apoptotic nuclei. At the irradiation dose of 1 J/cm 2 , the percentage of apoptotic cells was 80%, respectively. This study provided substantial evidence that Photolon preferentially localized in the subcellular organelles in the following order: nucleus, mitochondria, lysosomes and the Golgi apparatus and subsequent photodamage of the mitochondria and lysosomes played an important role in PDT-mediated apoptosis CT-26 cells. Our results based on the cytoplasmic organelles and the intranuclear localization extensively enhance the efficacy of PDT with appropriate photosensitizer and light dose and support the idea that PDT can contribute to elimination of malignant cells by inducing apoptosis, which is of physiological significance.

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Section: Introductionmentioning

confidence: 99%

Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes

Olivo

2011

Int J Oncol

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“…The complex of chlorin e6 with PVP increases its stability and improves its solubility in water, thereby increasing its bioavailability and enhancing its photosensitising effect . Moreover, the covalent attachment of chlorin e6 to a polymeric carrier enables a prolonged circulation of the drug in the plasma due to its increased molecular weight (Kaneda et al, 2004). This leads to passive tumour targeting by the "enhanced permeability and retention" (EPR) effect (Duncan, 2003).…”

Section: Introductionmentioning

confidence: 99%

Photolon™, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis

Copley

Watt

Wirtz

et al. 2008

The International Journal of Biochemistry & Cell Biology

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PhotolonTM is a photosensitiser with demonstrated potential as an anti-tumour agent. In this study, an in vitro investigation was performed to determine the mechanism of Photolon TM -induced cell death. Cell killing was observed in a light-dependent manner and light-activated Photolon TM resulted in a significant production of reactive oxygen species (ROS), which could be blocked by type I ROS scavengers. Inhibition of ROS production using Trolox prevented Photolon TM -induced cell death. Lightactivated Photolon TM caused no increase in caspase-3/7 activity, but a rapid increase in lactate dehydrogenase (LDH) release suggesting a loss of membrane integrity and subsequent cell death by necrosis. We conclude that the mechanism of Photolon TMinduced cell death involves the induction of ROS via a type I mechanism, which is ultimately responsible for cell killing by necrosis.

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“…8 Ishida et al have reported that although integration of polyethylene glycol (PEG) in the surface of nanoparticles lengthens the circulation time by allowing evasion of the macrophage system, their retention in vivo is still severely impaired. 9 As we previously reported, poly(N-vinylpyrrolidone) (PVP), a good alternative to PEG, 10,11 enhances the in vivo circulation time in that it evades the reticuloendothelial system more efficiently. 12 It was reported that PVP conjugated with tumor necrosis factor-α (TNF-α) showed longer blood circulation time than did PEG-conjugated TNF-α.…”

mentioning

confidence: 99%

Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

Zhang¹,

Zheng²,

Jing³

et al. 2015

IJN

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Previous reports have shown that ursolic acid (UA), a pentacyclic triterpenoid derived from Catharanthus trichophyllus roots, could inhibit the growth of a series of cancer cells. However, the potential for clinical application of UA is greatly hampered by its poor solubility, whereas the hydrophobicity of UA renders it a promising model drug for nanosized delivery systems. In the current study, we loaded UA into amphiphilic poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles and performed physiochemical characterization as well as analysis of the releasing capacity. In vitro experiments indicated that UA-NPs inhibited the growth of liver cancer cells and induced cellular apoptosis more efficiently than did free UA. Moreover, UA-NPs significantly delayed tumor growth and localized to the tumor site when compared with the equivalent dose of UA. In addition, both Western blotting and immunohistochemistry suggested that the possible mechanism of the superior efficiency of UA-NPs is mediation by the regulation of apoptosis-related proteins. Therefore, UA-NPs show potential as a promising nanosized drug system for liver cancer therapy.

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The use of PVP as a polymeric carrier to improve the plasma half-life of drugs

Cited by 181 publications

References 16 publications

Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes

Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes

Photolon™, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis

Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

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The use of PVP as a polymeric carrier to improve the plasma half-life of drugs

Cited by 181 publications

References 16 publications

Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes

Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes

Photolon™, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis

Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (&epsilon;-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

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Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo