Tissues from the pancreas, liver, spleen, heart, lung, and kidney were taken out and directly kept MK5108 clinical trial in liquid nitrogen. Then the mixed solution was kept static for 2 min and centrifuged at 5,000×g for 5 min at 4°C. After centrifugation at 5,000×g for 5 min at 4°C, the gemcitabine content in the supernatant was determined by high-performance liquid chromatography (HPLC), with a Diamond C18 chromatographic column (5 μm, ID 4.6 × 300 mm, Anoka, MN, USA) and at a flow rate of 1 mL/min. Toxic side effect OSI-027 in vitro assessment Both the high-dose (200 mg/kg) and low-dose (100 mg/kg) groups were constructed, as shown in Table 1. After administration for 3 weeks, each blood sample was collected from the arteriae femoralis. Different blood parameters, including white blood count (WBC), red blood cell count (RBC),

hemoglobin (Hb), alanine aminotransferase (ALT), BTSA1 datasheet aspartate aminotransferase (AST), creatinine (Cr), and urea (BUN), were measured using a biochemical autoanalyzer (Type 7170, Hitachi, Tokyo, Japan). The samples obtained from healthy

mice were used as control. Table 1 Blood parameters of SD rats treated with the different formulations for 3 weeks Parameters Formulation (n = 6, p > 0.05)   110-nm GEM-ANPs 406-nm GEM-ANPs Gemcitabine ANPs Control   Normal dose High dose Normal dose High dose Normal dose High dose High dose – WBC (109/L) 7.3 ± 1.1 5.3 ± 2.0 6.1 ± 1.2 5.1 ± 2.2 6.1 ± 1.3 4.8 ± 2.8 8.2 ± 2.2 7.3 ± 1.9 RBC (1012/L) 5.6 ± 1.8 6.2 ± 1.6 6.2 ± 2.1 6.1 ± 1.1 6.5 ± 2.9 6.0 ± 2.0 6.6 ± 2.9 6.4 ± 1.2 Hb (g/L) 130.0 ± 23.0 134.0 ± 20.0 141.0 ± 14.0 138.0 ± 16.0 139.0 ± 20.0 132.0 ± 16.0 148.0 ± 23.0 143.0 ± 19.0 ALT (U/L) 44.8 ± 14.0 52.5 ± 12.9 46.0 ± 11.3 54.3 ± 12.8 51.8 ± 15.3 60.2 ± 21.9 44.7 ± 11.5 48.8 ± 13.2 AST (U/L) 109.1 ± 22.1 128.0 ± 31.8 115.5 ± 26.0 113.1 ± 26.9 129.4 ± 28.1 136.3 ± 33.4 Protein kinase N1 113.3 ± 28.4 109.5 ± 25.7 Cr (mM/L) 7.1 ± 2.4 8.7 ± 3.2 6.2 ± 1.5 7.8 ± 2.07 6.1 ± 1.9 7.4 ± 2.2 4.9 ± 1.5 6.1 ± 1.6 BUN (μM/L) 41.0 ± 15.1 45.5 ± 17.3 35.4 ± 16.0 40.9 ± 19.5 36.1 ± 18.2 45.0 ± 13.7 47.2 ± 16.2 41.3 ± 18.6 Antitumor activity in vivo Tumor induction and drug administration Each male nude mice (n = 30) was injected subcutaneously in the back skin with 0.2 mL PANC-1 cell line (1.0 × 108/mL). Those mice were randomly divided into five groups (n = 6): Group A: 110-nm GEM-ANPs Group B: 406-nm GEM-ANPs Group C: pure gemcitabine Group D: blank ANPs Group E: control (0.9% NS) One week later, a tumor about 5 mm in diameter could be observed in the mice.