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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 concentration-time profiles of DTX in (A) heart, (B) liver, (C) spleen, (D) lung, (E) ovary/uterus, and (F) kidney, and following intravenous administration of a single 75 mg/m2 dose of DTX Polysorbate 80 micelles injection and DTX Polysorbate 80/Phospholipid mixed micelles injection to mice (Each point represents the Mean ± SD of four mice.).
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Figure 5: Mean concentration-time profiles of DTX in (A) heart, (B) liver, (C) spleen, (D) lung, (E) ovary/uterus, and (F) kidney, and following intravenous administration of a single 75 mg/m2 dose of DTX Polysorbate 80 micelles injection and DTX Polysorbate 80/Phospholipid mixed micelles injection to mice (Each point represents the Mean ± SD of four mice.).

Mentions: The DTX-AUC (DTX-area under curve) of the two preparations in different tissues, including plasma, heart, spleen, lung, ovary and uterus, kidney, and liver were calculated (Table 4). As shown in Figure 5, DTX was widely and rapidly distributed into most tissues following intravenous administration of the two micelle preparations. The DTX-AUC of Polysorbate 80/Phospholipid mixed micelles was higher in all tissues compared to the reference. The order in DTX-AUC from the highest to the lowest for DTX-loaded Polysorbate 80 micelles was kidney > lung > spleen > ovary and uterus > heart > liver > plasma. In contrast, the corresponding order for the DTX-loaded Polysorbate 80/Phospholipid mixed micelles was kidney > spleen > ovary and uterus > lung > heart > liver > plasma, and the DTX concentration in brain was too low to be detected.


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 concentration-time profiles of DTX in (A) heart, (B) liver, (C) spleen, (D) lung, (E) ovary/uterus, and (F) kidney, and following intravenous administration of a single 75 mg/m2 dose of DTX Polysorbate 80 micelles injection and DTX Polysorbate 80/Phospholipid mixed micelles injection to mice (Each point represents the Mean ± SD of four mice.).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Mean concentration-time profiles of DTX in (A) heart, (B) liver, (C) spleen, (D) lung, (E) ovary/uterus, and (F) kidney, and following intravenous administration of a single 75 mg/m2 dose of DTX Polysorbate 80 micelles injection and DTX Polysorbate 80/Phospholipid mixed micelles injection to mice (Each point represents the Mean ± SD of four mice.).
Mentions: The DTX-AUC (DTX-area under curve) of the two preparations in different tissues, including plasma, heart, spleen, lung, ovary and uterus, kidney, and liver were calculated (Table 4). As shown in Figure 5, DTX was widely and rapidly distributed into most tissues following intravenous administration of the two micelle preparations. The DTX-AUC of Polysorbate 80/Phospholipid mixed micelles was higher in all tissues compared to the reference. The order in DTX-AUC from the highest to the lowest for DTX-loaded Polysorbate 80 micelles was kidney > lung > spleen > ovary and uterus > heart > liver > plasma. In contrast, the corresponding order for the DTX-loaded Polysorbate 80/Phospholipid mixed micelles was kidney > spleen > ovary and uterus > lung > heart > liver > plasma, and the DTX concentration in brain was too low to be detected.

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