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.

Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis

“…The organic solvent was removed by vacuum rotary evaporation at 37 °C. FITC-HSA was conjugated as previously described 58 . Briefly, 10 mg of FITC and 2 mL of 20% (w/v) HSA were dissolved in carbonate buffer (0.05 M, pH 9.6) and stirred in dark for 9 h at room temperature.…”

Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

“…[6][7][8][9] Some co-delivery nanoparticles (NPs) have been established to load two small-molecule anticancer drugs, for example, pirarubicin and paclitaxel, 10 doxorubicin (DOX) and paclitaxel, 11 or cisplatin and rapamycin, 12 or a small-molecule drug plus a macromolecule anticancer drug, such as, protein, 13 miRNA, 14 DNA, 15 or gene agents. 5 Co-NDDS synergistically inhibited the growth of the tumor compared with free drugs.…”

Nanomedicine-Mediated Combination Drug Therapy in Tumor

“…Nanomedicine may solve this problem by maintaining the optimal synergistic ratio of the drugs, delivering them to the tumor simultaneously, and altering the pharmacokinetic and distribution profile in vivo because these are dependent on nanocarrier properties (rather than being dependent on the drugs themselves) [15]. Thus, nanomedicine-mediated combination drug therapy appears to be very promising for tumor treatment and there are several drugs currently in clinical trials.…”

“…Hyaluronic acid-decorated PLGA nanoparticles Breast cancer, squamous cell carcinoma [19] Paclitaxel and etoposide PEG-PLGA nanoparticles Osteosarcoma [20] Cisplatin and paclitaxel Folic acid modified PEG-PLGA nanoparticles Non-small lung cancer [21,22] Cisplatin and doxorubicin Transferrin modified PEG-PLGA nanoparticles Human hepatoma carcinoma [23] Combretastatin-A4 phosphate and doxorubicin mPEG-PLA nanoparticles Human nasopharyngeal epidermal carcinoma [24] Paclitaxel and tetrandrine CTAB@MSN Breast cancer [25] mPEG-PCL nanoparticles Gastric cancer [27] PEG-b-PCL nanoparticles Gastric cancer [28] Pirarubicin and paclitaxel Human serum albumin nanoparticles Breast cancer [15] Hypocrellin B and paclitaxel Hyaluronic acid-ceramide nanoparticles Lung cancer [29] Doxorubicin and paclitaxel mPEsG-b-PLG-b-PLL/DOCA nanovehicle Non-small cell lung cancer [30] PEG-PLGA and PEG-PLA nanoparticles have also been chemically altered to improve tumor targeting. For example, He et al [21,22] utilized folic acid (FA)-modified PEG-PLGA nanoparticles for the co-delivery of cisplatin (CDDP) and PTX.…”

“…Human serum albumin (HSA), a protein found in the human serum, is particularly suited as a nanocarrier material due to its non-toxicity, biocompatible, and biodegradable [26]. Yi et al [15] prepared a co-delivery system of PTX and pirarubicin (THP) by using HSA, and their results indicated that the nanoparticles had greater cytotoxicity against 4T1 breast cancer cells when compared with single or free drug delivery. Furthermore, the side effects of the drugs were significantly reduced, including bone marrow suppression, and organ or gastrointestinal toxicity.…”