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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

Particle size distributions of the micelles. (A) DTX-loaded Polysorbate 80 micelles; (B) Blank Polysorbate 80/Phospholipid mixed micelles; (C) DTX-loaded Polysorbate 80/Phospholipid mixed micelles.
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Figure 1: Particle size distributions of the micelles. (A) DTX-loaded Polysorbate 80 micelles; (B) Blank Polysorbate 80/Phospholipid mixed micelles; (C) DTX-loaded Polysorbate 80/Phospholipid mixed micelles.

Mentions: In order to achieve longevity during systemic circulation, the micelles must be small enough to evade detection and destruction of the reticuloendothelial system (RES). The mean diameter and the polydispersity coefficient (PDI) of DTX-loaded Polysorbate 80 micelles, blank Polysorbate 80/Phospholipid mixed micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles were 7.89 ± 1.97 nm and 0.234, 8.44 ± 2.34 nm and 0.319, 13.89 ± 3.52 nm and 0.089, respectively, which were measured by dynamic light scattering. It could be seen that the size distribution was relatively narrow (Figure 1). The hydrodynamic particle size of the drug-loaded micelles is understandably larger than the blank micelles, probably due to the incorporation of large and bulky drug molecules (Mw of DTX: 807.88 g/mol) within the core. Moreover, the particle size of the drug-loaded mixed micelles is larger than drug-loaded Polysorbate 80 single component micelles, it is still safely below 20 nm. There was no significant difference in particle size of these three types of micelles. The DTX-loaded Polysorbate 80/Phospholipid mixed micelles were dispersed in pure water and the morphology was investigated by TEM. These drug-loaded particles had a rod-like shape, which is one of the characteristic shapes of micelle. The particle surface was very smooth and no drug crystal was visible (Figure 2).


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)

Particle size distributions of the micelles. (A) DTX-loaded Polysorbate 80 micelles; (B) Blank Polysorbate 80/Phospholipid mixed micelles; (C) DTX-loaded Polysorbate 80/Phospholipid mixed micelles.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Particle size distributions of the micelles. (A) DTX-loaded Polysorbate 80 micelles; (B) Blank Polysorbate 80/Phospholipid mixed micelles; (C) DTX-loaded Polysorbate 80/Phospholipid mixed micelles.
Mentions: In order to achieve longevity during systemic circulation, the micelles must be small enough to evade detection and destruction of the reticuloendothelial system (RES). The mean diameter and the polydispersity coefficient (PDI) of DTX-loaded Polysorbate 80 micelles, blank Polysorbate 80/Phospholipid mixed micelles and DTX-loaded Polysorbate 80/Phospholipid mixed micelles were 7.89 ± 1.97 nm and 0.234, 8.44 ± 2.34 nm and 0.319, 13.89 ± 3.52 nm and 0.089, respectively, which were measured by dynamic light scattering. It could be seen that the size distribution was relatively narrow (Figure 1). The hydrodynamic particle size of the drug-loaded micelles is understandably larger than the blank micelles, probably due to the incorporation of large and bulky drug molecules (Mw of DTX: 807.88 g/mol) within the core. Moreover, the particle size of the drug-loaded mixed micelles is larger than drug-loaded Polysorbate 80 single component micelles, it is still safely below 20 nm. There was no significant difference in particle size of these three types of micelles. The DTX-loaded Polysorbate 80/Phospholipid mixed micelles were dispersed in pure water and the morphology was investigated by TEM. These drug-loaded particles had a rod-like shape, which is one of the characteristic shapes of micelle. The particle surface was very smooth and no drug crystal was visible (Figure 2).

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