Co-delivery of Pirarubicin and Paclitaxel by Human Serum Albumin Nanoparticles to Enhance Antitumor Effect and Reduce Systemic Toxicity in Breast Cancers

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• 作者：Xiaoli Yi ; Xianghong Lian ; Jianxia Dong ; Zhuoya Wan ; Chunyu Xia ; Xu Song ; Yao Fu ; Tao Gong ; Zhirong Zhang
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：November 2, 2015
• 年：2015
• 卷：12
• 期：11
• 页码：4085-4098
• 全文大小：945K
• ISSN：1543-8392

文摘

In our study, we aimed to develop a codelivery nanoparticulate system of pirarubicin (THP) and paclitaxel (PTX) (Co-AN) using human serum albumin to improve the therapeutic effect and reduce systemic toxicities. The prepared Co-AN demonstrated a narrow size distribution around 156.9 卤 3.2 nm (PDI = 0.16 卤 0.02) and high loading efficiency (87.91 卤 2.85% for THP and 80.20 卤 2.21% for PTX) with sustained release profiles. Significantly higher drug accumulation in tumors and decreased distribution in normal tissues were observed for Co-AN in xenograft 4T1 murine breast cancer bearing BALB/c mice. Cytotoxicity test against 4T1 cells in vitro and antitumor assay on 4T1 breast cancer in vivo demonstrated that the antitumor effect of Co-AN was superior to that of the single drug or free combination. Also, Co-AN induced increased apoptosis and G2/M cell cycle arrest against 4T1 cells compared to that of the single drug formulation. Remarkably, Co-AN exhibited significantly lower side effects regarding bone marrow suppression and organ and gastrointestinal toxicities. This human serum albumin-based codelivery system represents a promising platform for combination chemotherapy in breast cancers.