title: Co-delivery of Pirarubicin and Paclitaxel by Human Serum Albumin Nanoparticles to Enhance Antitumor Effect and Reduce Systemic Toxicity in Breast Cancers.
abstract: 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.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yi
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lian
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Dong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Zhuoya
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Xia
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Song
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Sichuan, People's Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005767:Gastrointestinal Diseases / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D012709:Serum Albumin; D004317:Doxorubicin; C027260:pirarubicin; D017239:Paclitaxel
keywords: combination chemotherapy; human serum albumin nanoparticles; paclitaxel; pirarubicin; synergistic effect; toxicity