Characterization and pharmacokinetics of a novel pirarubicin liposome powder

Abstract

Background: Pirarubicin (THP), an analogue of doxorubicin, has exhibited promising activities against acute leukemia, malignant lymphoma, and several solid tumors. However, the cumulative cardiotoxicity limits its wide application in chemotherapy. Method: To provide an alternative strategy for reducing the cardiotoxicity, a novel THP liposome powder (L-THP), comprising distearoylphosphatidylcholine, distearoylphosphatidylglycerol, cholesterol, and lactose was appropriately prepared based on the physicochemical properties of THP. And L-THP was characterized and evaluated. Comparative studies on pharmacokinetic and biodistribution behaviors between L-THP and commercialized THP injection were performed in normal mice through intravenous administration. Results: When L-THP was reconstituted in a proper amount of normal saline for injection, it had a mean diameter of around 220.0 nm, a zeta potential of about −33.0 mV, and a high THP entrapment efficiency of more than 93.1%. Pharmacokinetics study showed that heart accumulation of THP could be reduced by 81.2% for L-THP. Conclusion: These results suggest that our L-THP might greatly reduce the cardiotoxicity, thus improving the therapeutic index of THP. Meanwhile, further preclinical studies are warranted to define the cardiotoxicity and the therapeutic efficacy of L-THP.

Keywords:

• Cardiotoxicity
• characterization
• liposome powder
• pharmacokinetics
• pirarubicin

Acknowledgments

This work was supported by grants from the Natural Science Foundation of China (NSFC: 30500666) and Yuyuan Foundation of Biomedicine Institute, Tsinghua University (NO: 20240000529 and 20240000548). We also wish to thank J.J. Zhu (Pharmaceutical Department, Hunan University of Traditional Chinese Medicine, Changsha, China) and Dr. X. Li (School of Medicine, Tsinghua University, Beijing, China) for their kind assistance in the animal experiments and Prof. Q.S. Zheng (Drug Evaluation Center of Shanghai University of Traditional Chinese Medicine, Shanghai, China) for his support in the statistics analysis.