Preclinical evaluations of norcantharidin-loaded intravenous lipid microspheres with low toxicity.
Expert Opin Drug Deliv
; 9(12): 1449-62, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-22971185
ABSTRACT
OBJECTIVES:
The aim of this study was to perform a systematic preclinical evaluation of norcantharidin (NCTD)-loaded intravenous lipid microspheres (NLM). RESEARCH DESIGN ANDMETHODS:
Pharmacokinetics, biodistribution, antitumor efficacy and drug safety assessment (including acute toxicity, subchronic toxicity, hemolysis testing, intravenous stimulation and injection anaphylaxis) of NLM were carried out in comparison with the commercial product disodium norcantharidate injection (NI).RESULTS:
The pharmacokinetics of NLM in rats was similar to that of NI, and a non-linear correlation was observed between AUC and dose. A comparable antitumor efficacy of NLM and NI was observed in mice inoculated with A549, BEL7402 and BCAP-37 cell lines. It was worth noting that the NLM produced a lower drug concentration in heart compared with NI, and significantly reduced the cardiac and renal toxicity. The LD(50) of NLM was twice higher than that of NI. In NLM, over 80% of NCTD was loaded in the lipid phase or bound with phospholipids. Thus, NCTD was sequestered by direct contacting with body fluids and largely avoided distribution into tissues, consequently leading to significantly reduced cardiac and renal toxicity.CONCLUSIONS:
These preclinical results suggested that NLM could be a useful potential carrier for parenteral administration of NCTD, while providing a superior safety profile.
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Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
/
Compostos Bicíclicos Heterocíclicos com Pontes
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Emulsões Gordurosas Intravenosas
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Antineoplásicos
Idioma:
En
Revista:
Expert Opin Drug Deliv
Ano de publicação:
2012
Tipo de documento:
Article