Pharmacokinetics and antitumor effects of vincristine carried by microemulsions composed of PEG-lipid, oleic acid, vitamin E and cholesterol.
In this study, injectable microemulsions of vincristine (M-VCR) were prepared and its pharmacokinetics, acute toxicity and antitumor effects were evaluated. In M-VCR, the surfactants were PEG-lipid and cholesterol, the oil phase was a vitamin E solution of oleic acid and VCR. The particle size distribution and zeta potential of M-VCR were measured by the laser light dynamic scattering method. The VCR-loading efficiency was measured by Sephadex G50 column chromatography. The stability of M-VCR was monitored by particle size, VCR-loading efficiency and VCR content changes of M-VCR stored at 7 degrees C. The pharmacokinetics, acute toxicity and antitumor effects of M-VCR were studied in C57BL/6 mice bearing mouse murine histocytoma M5076 tumors. When stored at 7 degrees C in the dark for 1 year, the average diameter and VCR-loading efficiency of M-VCR changed from 138.1+/-1.2 nm and 94.6+/-4.7% to 127.1+/-2.4 nm and 91.3+/-4.8% (n=3), respectively, while 7.4+/-0.3% VCR decomposition was observed (n=3). The plasma AUC of M-VCR was significantly greater than that of free VCR (F-VCR). The heart, spleen and liver AUC(0.08-12 h) of M-VCR were significantly smaller than those of F-VCR while the kidney AUC(0.08-12 h) of M-VCR was significantly greater than that of F-VCR. The tumor AUC(0.08-12 h) of M-VCR was significantly greater than that of F-VCR. M-VCR had lower acute toxicity and greater potential antitumor effects than F-VCR in M5076 tumor-bearing C57BL/6 mice. M-VCR is a useful tumor-targeting microemulsion drug delivery system.
Junping
Wang
W
Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
Takayama
Kozo
K
Nagai
Tsuneji
T
Maitani
Yoshie
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002784:Cholesterol / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004655:Emulsions; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019301:Oleic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014810:Vitamin E / Q000008:administration & dosage / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D004655:Emulsions; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D014810:Vitamin E; D019301:Oleic Acid; D011092:Polyethylene Glycols; D014750:Vincristine; D002784:Cholesterol