2005
DOI: 10.1007/s00280-005-0091-7 View full text |Buy / Rent full text
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Abstract: The studies presented here indicate that intravenous administration of IT-101, a cyclodextrin based polymer-CPT conjugate, gives prolonged plasma half-life and enhanced distribution to tumor tissue when compared to CPT alone. The data also show that active CPT is released from the conjugate within the tumor for an extended period of time. These effects likely play a significant role in the enhanced antitumor activity of IT-101 when compared to CPT alone or irinotecan.

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“…The synthesis and properties of preclinical nanoparticles of CRLX101 have been described previously (12)(13)(14)(15)(16)(17)(18). The nanoparticles were 20 to 30 nm in diameter, and characterization studies demonstrated that all the polymer chains were contained within the nanoparticles (i.e., no free polymer chains) (13).…”
Section: Resultsmentioning
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“…The synthesis and properties of preclinical nanoparticles of CRLX101 have been described previously (12)(13)(14)(15)(16)(17)(18). The nanoparticles were 20 to 30 nm in diameter, and characterization studies demonstrated that all the polymer chains were contained within the nanoparticles (i.e., no free polymer chains) (13).…”
Section: Resultsmentioning
“…However, the biodistribution of CRLX101 has been investigated in animals, and accumulations in kidney, liver, and spleen are observed in addition to tumor (13,14). In mice, the total amount of CPT per gram of tissue (14) and polymer (that is indicative of CRLX101 nanoparticles) are the highest in the tumor tissue at 24 h after administration (13). Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans.…”
Section: Discussionmentioning
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“…These effects likely play a significant role in the enhanced antitumour activity of CRLX101 when compared to CPT alone or CPT-11. 138 Notably, CRLX101 tumour growth inhibition of squamous and nonsquamous NSCLC was superior to approved therapeutic agents such as TPT, docetaxel (Taxotere s ; Aventis), erlotinib (Tarceva s ), gemcitabine (Gemzar s ; Lilly) and carboplatin (Paraplatin s ; Bristol-Myers Squibb). Thanks to its sustained levels within penetrated tumour tissue, CRLX101 inhibited cell proliferation uniformly.…”
Section: Crlx101 Preclinical Resultsmentioning