Abstract：
PURPOSE:A novel photo-activated targeted chemotherapy was developed by photochemical internalization (PCI) of glutathione-sensitive polymeric micelles incorporating camptothecin (CPT) prepared from thiolated CPT (CPT-DP) and thiolated poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-P(Glu-DP)) METHODS: PEG-b-P(Glu-DP) and CPT-DP were synthesized and characterized by (1)H-NMR and gel permeation chromatography, and then mixed to prepare CPT-loaded polymeric micelles (CPT/m). The CPT release from the micelle was studied by reverse phase liquid chromatography. The PCI-activated cytotoxicity of CPT/m against HeLa cells was studied in combination with a non-toxic concentration of dendrimer phthalocyanine-loaded micelles (DPc/m) as the photosensitizer. RESULTS:The diameter of CPT/m was 96 nm and the drug loading was 20% (w/w). CPT was slowly released under the conditions reproducing the extracellular or endosomal environments. However, under the reductive conditions mimicking the cytosol, CPT was rapidly released achieving approximately 90% of the drug release after 24 h. The cytotoxicity of CPT/m was drastically increased on photoirradiation, whereas the CPT/m were not cytotoxic without PCI. CONCLUSIONS:The CPT/m released the drug responding to reductive conditions. The PCI-induced endosomal escape exposed CPT/m to the cytosol triggering the drug release. Thus, CPT/m in combination with DPc/m will behave as smart nanocarriers activated only at photoirradiated tissues.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Cabral H,Nakanishi M,Kumagai M,Jang WD,Nishiyama N,Kataoka Kdoi
10.1007/s11095-008-9712-2subject
Has Abstractpub_date
2009-01-01 00:00:00pages
82-92issue
1eissn
0724-8741issn
1573-904Xjournal_volume
26pub_type
杂志文章abstract：PURPOSE:To examine the theoretical/practical utility of the liver-to-blood partition coefficient (Kpuu) for predicting drug-drug interactions (DDIs), and compare the Kpuu-approach to the extended clearance concept AUCR-approach. METHODS:The Kpuu relationship was derived from first principles. Theoretical simulations i...
journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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更新日期：2013-06-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015948829632
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-009-9852-z
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journal_title：Pharmaceutical research
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更新日期：1996-05-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/a:1015393710253
更新日期：2002-05-01 00:00:00
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更新日期：2015-09-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/b:pham.0000016251.42392.1e
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更新日期：2014-06-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1999-09-01 00:00:00
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更新日期：2009-01-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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更新日期：2010-07-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2003-12-01 00:00:00
abstract：PURPOSE:Models to predict membrane-water partition coefficients (Kp) as a function of drug structure, membrane composition, and solution properties would be useful. This study explores the partitioning of dexamethasone (Dex) and its ionizable 21-phosphate (Dex-P) in liposomes varying in acyl chain length, physical stat...
journal_title：Pharmaceutical research
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更新日期：2013-12-01 00:00:00
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更新日期：2011-02-01 00:00:00
