RRC ID 43500
著者 Ohguchi Y, Kawano K, Hattori Y, Maitani Y.
タイトル Selective delivery of folate-PEG-linked, nanoemulsion-loaded aclacinomycin A to KB nasopharyngeal cells and xenograft: effect of chain length and amount of folate-PEG linker.
ジャーナル J Drug Target
Abstract To investigate the use of folate-targeted nanoemulsion-loaded aclacinomycin A (ACM) to folate receptor (FR)-positive cells, we attempted to optimize the targeting ability of nanoemulsions by modifying the chain length and amount of the folate-PEG linker. Folate-linked, nanoemulsion-loaded ACM were formulated with 0.24 mol% of folate-poly (ethylene glycol)(3400)- (folate-PEG(3400)-) and folate-PEG(5000)-distearoylphosphatidylethanolamine (DSPE), and 0.03 mol% of folate-PEG(5000)-DSPE in nanoemulsions. Selective FR-mediated uptake was achieved in a human nasopharyngeal tumor cell line, KB, which overexpresses FR, but not in a human hepatoblastoma cell line, (FR(-)) HepG2. At the same amount of folate modification, the association with KB cells was increased with increasing the PEG-chain length. The association of 0.03 and 0.24 mol% folate-PEG(5000)-linked nanoemulsions with cells was 5- and 3.3-fold higher than that of non-folate nanoemulsion, respectively, while their cytotoxicity was similar. Both 0.03 and 0.24 mol% folate-PEG(5000)-linked nanoemulsions and non-folate nanoemulsion following intravenous injection inhibited tumor growth more significantly than ACM solution on day 24 following tumor inoculation (p < 0.01). This study demonstrates that a folate-linked nanoemulsion is feasible for tumor-targeted ACM delivery, and that folate modification with a sufficiently long PEG-chain and a small amount of nanoemulsion is an effective way of targeting nanoemulsion to tumor cells.
巻・号 16(9)
ページ 660-7
公開日 2008-11-1
DOI 10.1080/10611860802201464
PII 905036358
PMID 18982514
MeSH Aclarubicin / chemistry* Aclarubicin / pharmacology* Animals Antibiotics, Antineoplastic / chemistry* Antibiotics, Antineoplastic / pharmacology Cell Line, Tumor Dose-Response Relationship, Drug Drug Delivery Systems Female Folic Acid / chemistry* Folic Acid / pharmacology Humans Mice Mice, Nude Nanostructures Nasopharynx / cytology Neoplasms / drug therapy Polyethylene Glycols / chemistry* Polyethylene Glycols / pharmacology Specific Pathogen-Free Organisms Transplantation, Heterologous
IF 3.38
引用数 38
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 Hep G2