Journal
MOLECULAR PHARMACEUTICS
Volume 12, Issue 11, Pages 4085-4098Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00536
Keywords
combination chemotherapy; human serum albumin nanoparticles; pirarubicin; paclitaxel; synergistic effect; toxicity
Funding
- National Basic Research Program of China (973 program) [2013CB932504]
- National S&T Major Project of China [2012ZX09304004]
- Sichuan University Startup Foundation for Talents [2082204174131]
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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 +/- 3.2 nm (PDI = 0.16 +/- 0.02) and high loading efficiency (87.91 2.85% for THP and 80.20 +/- 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.
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