We found that GEM-ANPs could result in a sustained Sapitinib order release and improved antitumor activity in vitro of gemcitabine. Here, we further exposed human pancreatic carcinoma (PANC-1) to GEM-ANPs and studied cell responses in vitro by cell viability analysis and flow cytometry technique. The loading of gemcitabine on albumin did not reduce the inhibition effect of gemcitabine on PANC-1 metabolism. Moreover, GEM-ANPs with bigger size could even enhance the killing efficacy of gemcitabine in pancreatic carcinoma (Figure 1). GEM-ANPs

showed their cell cycle inhibitory property, in the order of 406-nm GEM-ANPs > 110-nm GEM-ANPs > gemcitabine. The higher antiproliferative activity of 406-nm GEM-ANPs could be attributed to the S phase arrest during cell cycle progression (Table 2). Besides the shorter half-life, the toxic side effects, like increased liver enzymes and leukopenia, have also limited the applications of gemcitabine [24]. Therefore, the blood parameters of rats treated with GEM-ANPs were investigated to assess the reduction effect of albumin loading on gemcitabine toxic side effects. Since the blank nanoparticles could interfere with the selleckchem growth of cells in vitro, the US Pharmacopoeia limits cell inhibition as no more than 50% for safety [25]. The present study revealed that no significant difference between the ANP

treatment group and control group was observed PDK4 in WBC, RBC, and other parameters of hepatonephric functions, suggesting a satisfactory biocompatibility Selleck ACY-738 (Table 1). What was more important was that the high-dose treatment with GEM-ANPs, especially 406-nm GEM-ANPs, could reduce the side effects of gemcitabine (Table 1). In fact, gemcitabine concentration and treatment period were insufficient to induce a relevant blood toxicity in the present study [26]. Our results also demonstrated that gemcitabine loading on 406-nm GEM-ANPs significantly increased the gemcitabine content in the pancreas, liver, and spleen of SD rats compared with the gemcitabine treatment

group, but contrary to 110-nm GEM-ANPs (p < 0.05) (Table 3). It is well known that nanospheres are easily taken up by cells of the mononuclear phagocyte system, primarily those located in the reticuloendothelial system-rich organs, such as the liver and spleen [27]. Furthermore, phagocytosis will gradually increase as the size is more than 200 nm [28]. Consequently, it might be one of the reasonable mechanisms for the targeting effect of 406-nm GEM-ANPs in vivo[29]. That was to say, 406-nm GEM-ANPs would enhance the curative effect of gemcitabine in pancreatic cancer. Particularly, literatures have reported that the microvascular permeability of most normal tissues was generally less than 50 nm, but ten times higher in tumor tissues and usually more than 500 nm. For example, Hobbs et al.