期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 61, 期 13, 页码 1193-1202出版社
ELSEVIER
DOI: 10.1016/j.addr.2009.01.007
关键词
Polymer; Camptothecin; Topoisomerase I inhibitor; Drug delivery; Dual phase release; Nanotechnology
An overview of XMT-1001 is provided in the context of other topoisomerase I inhibitors conjugated to polymers or encapsulated in liposomes. XMT-1001 is a novel polymeric pro-drug derivative of camptothecin (CPT) with a molecular weight of 70 kDa, in which CPT is chemically tethered to a hydrophilic, biodegradable polyacetal polymer, poly(1-hydroxymethylethylene hydroxymethylformal), also called PHF or Fleximer (R). XMT-1001 releases CPT via intermediates camptothecin-20-O-(N-succinimidoglycinate).(CPT-SI), and camptothecin-20-0-(N-succinamidoyl-glycinate) (CPT-SA) over an extended time period. XMT-1001 has an improved therapeutic window compared to CPT and irinotecan in human tumor xenograft models, providing a compelling rationale for clinical development. A unique feature of XMT-1001 is its dual phase release mechanism for CPT which may result in lower levels of CPT in the urine and less bladder toxicity, a serious dose limiting toxicity associated with CPT and CPT conjugated to other polymers. XMT-1001 is being evaluated in patients with advanced cancer in an ongoing Phase 1 trial. (C) 2009 Elsevier B.V. All rights reserved.
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