Toxicity studies of cremophor-free paclitaxel solid dispersion formulated by a supercritical antisolvent process
DC Field | Value | Language |
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dc.contributor.author | Park, Jae-Hyun | - |
dc.contributor.author | Chi, Sang-Cheol | - |
dc.contributor.author | Lee, Won Seok | - |
dc.contributor.author | Lee, Won Mo | - |
dc.contributor.author | Koo, Yoon Bon | - |
dc.contributor.author | Yong, Chul Soon | - |
dc.contributor.author | Choi, Han Gon | - |
dc.contributor.author | Woo, Jong Soo | - |
dc.date.accessioned | 2021-06-23T16:03:53Z | - |
dc.date.available | 2021-06-23T16:03:53Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2009-01 | - |
dc.identifier.issn | 0253-6269 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/41465 | - |
dc.description.abstract | To evaluate the acute toxicity of a paclitaxel solid dispersion formulation, single dose studies in ICR mice were carried out for injectable excipients, paclitaxel solid dispersion powder, and TaxolA (R). In the dose range of excipients used for preparing paclitaxel solid dispersion, each excipient was clinically safe, and the LD50 for exicipients was higher than 2,000 mg/kg for both males and females. In this study, there were no remarkable clinical signs or deaths related to paclitaxel solid dispersion even at doses up to 160 mg/kg of paclitaxel. But TaxolA (R) resulted in clinical signs when it contained more than 30 mg/mL paclitaxel. The LD50 for paclitaxel solid dispersion was above 160 mg/kg and the LD50 for TaxolA (R) was 31.3 mg/kg, more than 5 times lower than that of paclitaxel solid dispersion. However, paclitaxel solid dispersion could not be administered i.v. at a dose exceeding 160 mg/kg, because of high viscosity. To evaluate the nephrotoxicity of paclitaxel solid dispersion, plasma level of creatinine and kidney weight were measured and compared to TaxolA (R). At the doses administered, paclitaxel solid dispersion did not change creatinine clearance, while TaxolA (R) killed all animals at doses > 15 mg/kg. To investigate membrane damage when paclitaxel formulations were injected, hemolytic activity was determined for different concentrations. Paclitaxel solid dispersion showed about 10% hemolytic activity, whereas TaxolA (R) showed about 40% hemolytic activity when it contained 2 mg of paclitaxel. Comparisons with the LD50 value, nephrotoxicity, and hemolytic activity of TaxolA (R) suggested that Cremophor-free paclitaxel solid dispersion as an injectable formulation is a promising approach to increasing the safety and clinical efficacy of paclitaxel for treatment of cancer. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PHARMACEUTICAL SOC KOREA | - |
dc.title | Toxicity studies of cremophor-free paclitaxel solid dispersion formulated by a supercritical antisolvent process | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Han Gon | - |
dc.identifier.doi | 10.1007/s12272-009-1128-y | - |
dc.identifier.scopusid | 2-s2.0-59449099561 | - |
dc.identifier.wosid | 000262851700018 | - |
dc.identifier.bibliographicCitation | ARCHIVES OF PHARMACAL RESEARCH, v.32, no.1, pp.139 - 148 | - |
dc.relation.isPartOf | ARCHIVES OF PHARMACAL RESEARCH | - |
dc.citation.title | ARCHIVES OF PHARMACAL RESEARCH | - |
dc.citation.volume | 32 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 139 | - |
dc.citation.endPage | 148 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART001312455 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | HYPERSENSITIVITY REACTIONS | - |
dc.subject.keywordPlus | ANTITUMOR AGENTS | - |
dc.subject.keywordPlus | TAXOL | - |
dc.subject.keywordPlus | EL | - |
dc.subject.keywordPlus | 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN | - |
dc.subject.keywordPlus | CONTAINERS | - |
dc.subject.keywordPlus | HEMOLYSIS | - |
dc.subject.keywordPlus | ETHANOL | - |
dc.subject.keywordAuthor | Paclitaxel | - |
dc.subject.keywordAuthor | Solid dispersion | - |
dc.subject.keywordAuthor | Toxicity | - |
dc.subject.keywordAuthor | LD50 | - |
dc.subject.keywordAuthor | Taxol | - |
dc.subject.keywordAuthor | Nephrotoxicity | - |
dc.identifier.url | https://link.springer.com/article/10.1007%2Fs12272-009-1128-y | - |
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