PEGylated lipid microspheres loaded with cabazitaxel for intravenous administration: stability, bioavailability, antitumor efficacy, and toxicity

Drug Delivery and Translational Research
Yang LiuJingxin Gou

Abstract

This paper aimed to develop a novel lipid microsphere delivering cabazitaxel (CTX) using phosphatidylcholine combined with DSPE-PEG2000 as emulsifier, and evaluate its stability, pharmacokinetics, antitumor efficacy, and toxicity. The pegylated cabazitaxel-loaded lipid microspheres (CTX-PLMs) were prepared by high-pressure homogenization methods; the biological samples were analyzed by the UPLC-MS/MS method. CTX-PLMs had a drug concentration of 1.2 mg/ml and a mean particle size of 180.0 ± 51.119 nm. CTX-PLMs showed a superior physical stability as it could remain nearly intact after 1-year storage. The AUC0-t of the CTX-PLMs was 1562.6 ± 520.1 μg h L-1 compared with the CTX-solution of 860.734 ± 312.4 μg h L-1. CTX-PLMs exhibited a strong antitumor efficacy against NCI-N87 and DU145 tumor models with tumor growth inhibition rates of 93.5 and 88.5%, respectively. The LD50 of CTX-PLMs in rats was 20.89 mg/kg. As for the long-term toxicity, the thymus, mesenteric lymph nodes, and bone marrow were the main toxic target organs and systemic toxicity induced by CTX-PLMs was alleviated relative to that of the CTX-solution. Safety assessment studies including hemolysis test, dermal sensitization test, systemic anaphylaxis, and vascular...Continue Reading

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Citations

Aug 18, 2020·International Journal of Nanomedicine·Zhong WanHai Zhang
Sep 3, 2020·International Journal of Pharmaceutics·Zimeng YangYongjun Wang
Nov 19, 2021·Journal of Nanobiotechnology·Jingbo HuJin Liu

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Methods Mentioned

BETA
xenograft
PCA

Software Mentioned

DAS
Statistical Program for Social Sciences ( SPSS )

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Anaphylaxis

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.