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Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models.

Song H, Geng H, Ruan J, Wang K, Bao C, Wang J, Peng X, Zhang X, Cui D - Nanoscale Res Lett (2011)

Bottom Line: In the pharmacokinetics assessment, there was no significant difference between the two preparations (P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process.However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver.In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Bio-Nano Science and Engineering, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China. dxcui@sjtu.edu.cn.

ABSTRACT
Docetaxel (DTX) is a very important member of taxoid family. Despite several alternative delivery systems reported recently, DTX formulated by Polysorbate 80 and alcohol (Taxotere®) is still the most frequent administration in clinical practice. In this study, we incorporated DTX into Polysorbate 80/Phospholipid mixed micelles and compared its structural characteristics, pharmacokinetics, biodistribution, and blood compatibility with its conventional counterparts. Results showed that the mixed micelles loaded DTX possessed a mean size of approximately 13 nm with narrow size distribution and a rod-like micelle shape. In the pharmacokinetics assessment, there was no significant difference between the two preparations (P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process. However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver. The blood compatibility assessment study revealed that the mixed micelles were safe for intravenous injection. In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX.

No MeSH data available.


Related in: MedlinePlus

Mean plasma concentration-time profiles of DTX after i.v. administration of a single 75 mg/m2 dose of DTX-loaded Polysorbate 80 micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles to rats (Each point represents the mean ± SD of six rats.).
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Figure 3: Mean plasma concentration-time profiles of DTX after i.v. administration of a single 75 mg/m2 dose of DTX-loaded Polysorbate 80 micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles to rats (Each point represents the mean ± SD of six rats.).

Mentions: The drug concentration of rats' plasma was detected by HPLC analysis, which has been validated with a linear calibration curve in the range of 10 to 6000 ng/mL of DTX and the correlation coefficient over this concentration range was 0.9996. The plasma concentration time profiles of DTX in rat plasma after intravenous administration of DTX-loaded Polysorbate 80 micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles at a single dose of 75 mg/m2 were compared (Figure 3). The profiles showed a rapid decline in the first 1 h (distribution phase) after dosing the two preparations. Furthermore, the DTX concentration versus time plots was obtained by means of a three compartmental model with the weight coefficient of 1/C2 based on computer program 3p87. The pharmacokinetic parameters are shown in Table 1 and analyzed for statistical significance by unpaired Student's t-test. The results of the statistical analysis proved the pharmacokinetic parameters were no significant difference (P > 0.05) between the two preparations. These data demonstrated that the DTX in Polysorbate 80 micelles and the DTX in Polysorbate 80/Phospholipid mixed micelles can achieve a similar pharmacokinetic process in rats.


Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models.

Song H, Geng H, Ruan J, Wang K, Bao C, Wang J, Peng X, Zhang X, Cui D - Nanoscale Res Lett (2011)

Mean plasma concentration-time profiles of DTX after i.v. administration of a single 75 mg/m2 dose of DTX-loaded Polysorbate 80 micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles to rats (Each point represents the mean ± SD of six rats.).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3211444&req=5

Figure 3: Mean plasma concentration-time profiles of DTX after i.v. administration of a single 75 mg/m2 dose of DTX-loaded Polysorbate 80 micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles to rats (Each point represents the mean ± SD of six rats.).
Mentions: The drug concentration of rats' plasma was detected by HPLC analysis, which has been validated with a linear calibration curve in the range of 10 to 6000 ng/mL of DTX and the correlation coefficient over this concentration range was 0.9996. The plasma concentration time profiles of DTX in rat plasma after intravenous administration of DTX-loaded Polysorbate 80 micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles at a single dose of 75 mg/m2 were compared (Figure 3). The profiles showed a rapid decline in the first 1 h (distribution phase) after dosing the two preparations. Furthermore, the DTX concentration versus time plots was obtained by means of a three compartmental model with the weight coefficient of 1/C2 based on computer program 3p87. The pharmacokinetic parameters are shown in Table 1 and analyzed for statistical significance by unpaired Student's t-test. The results of the statistical analysis proved the pharmacokinetic parameters were no significant difference (P > 0.05) between the two preparations. These data demonstrated that the DTX in Polysorbate 80 micelles and the DTX in Polysorbate 80/Phospholipid mixed micelles can achieve a similar pharmacokinetic process in rats.

Bottom Line: In the pharmacokinetics assessment, there was no significant difference between the two preparations (P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process.However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver.In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Bio-Nano Science and Engineering, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China. dxcui@sjtu.edu.cn.

ABSTRACT
Docetaxel (DTX) is a very important member of taxoid family. Despite several alternative delivery systems reported recently, DTX formulated by Polysorbate 80 and alcohol (Taxotere®) is still the most frequent administration in clinical practice. In this study, we incorporated DTX into Polysorbate 80/Phospholipid mixed micelles and compared its structural characteristics, pharmacokinetics, biodistribution, and blood compatibility with its conventional counterparts. Results showed that the mixed micelles loaded DTX possessed a mean size of approximately 13 nm with narrow size distribution and a rod-like micelle shape. In the pharmacokinetics assessment, there was no significant difference between the two preparations (P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process. However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver. The blood compatibility assessment study revealed that the mixed micelles were safe for intravenous injection. In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX.

No MeSH data available.


Related in: MedlinePlus