Antitumor Effect and Toxicity of an Albumin-Paclitaxel Nanocarrier System Constructed via Controllable Alkali-Induced Conformational Changes.

Various strategies have been developed to construct albumin nanomaterials via biophysical or chemical changes. In this work, a compound comprising albumin-paclitaxel nanoparticles (NPs-PTX) with a drug loading efficiency of 21% was constructed via manipulation of alkali induced conformation changes and hydrophilic-hydrophobicity transition. The toxicity of two PTX formulations (Taxol and NPs-PTX) in human umbilical vein endothelial cells (HUVECs), RAW264.7, K562, and HepG2 cells, and rats were determined. The half maximal inhibitory concentration (IC) of Taxol was remarkably lower than that of NPs-PTX. Both PTX formulations promoted cell apoptosis, possibly via mitochondria-dependent (intrinsic) and mitochondria-independent pathways. The effect of PTX formulations (0.5 to 1 mg mL) on hemolysis and the median lethal dose (50% mortality, LD) values of the PTX formulations were significantly different ( < 0.01). Reductions in the number of white blood cells (WBCs) and monocytes (MNCs) and obvious pathological changes in the spleen, thymus, and mesenteric lymph nodes were observed and may have been related to the bone marrow inhibition effect of PTX. The tumor inhibition rate of NPs-PTX (60.8%) was higher than that of Taxol (31.2%) ( < 0.05) when the dose of NPs-PTX (equivalent PTX) was 2.5 times as that of Taxol (30 vs 12 mg kg). Taxol is highly toxic, whereas NPs-PTX is moderately toxic. Thus, NPs-PTX has advantages over the commercially available Taxol formulation in terms of low toxicity and increased dosage, indicating NPs-PTX is a better option for safe and effective PTX delivery.