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

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.

Self-assembled micelles of novel amphiphilic copolymer cholesterol-coupled F68 containing cabazitaxel as a drug delivery system

“…27,[30][31][32] Because of its simplicity, the self-assembly method is recognized as being outstanding, and has the potential for clinical application. 27 In this study, we used the self-assembly method to prepare drug-loaded micelles. The micelles were clear and colorless with a high EE of 98.1%.…”

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112

“…This is consistent with the notion that nanoparticles possess the ability of targeting the macrophage system and can accumulate in the liver and spleen. 53 The pharmacokinetic curves of the nanocrystals and cosolvent show a high similarity ( Figure 5A). The fact that the nanocrystals did not markedly alter the pharmacokinetic profile of SNX-2112 was due to immediate drug release from the nanocrystals upon intravenous administration ( Figure 9).…”

Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

“…23 TN and mPEG 2000 -DSPE (3:4, molar ratio) were dispersed in 0.5 mL of absolute ethanol, and sterile water was added to the homogeneous phase to achieve a clear, injectable micelle solution of volume 8 mL. The final solution was filtered through a polycarbonate membrane with a pore size of 0.22 μm.…”