Abstract
With the development of nanotechnology, special attention has been given to the nanomaterial application in tumor treatment. Here, a modified desolvation-cross-linking method was successfully applied to fabricate gemcitabine-loaded albumin nanospheres (GEM-ANPs), with 110 and 406 nm of mean diameter, respectively. The aim of this study was to assess the drug distribution, side effects, and antitumor activity of GEM-ANPs in vivo. The metabolic viability and flow cytometry analysis revealed that both GEM-ANPs, especially 406-nm GEM-ANPs, could effectively inhibit the metabolism and proliferation and promote the apoptosis of human pancreatic carcinoma (PANC-1) in vitro. Intravenous injection of 406-nm GEM-ANPs exhibited a significant increase of gemcitabine in the pancreas, liver, and spleen of Sprague–Dawley rats (p < 0.05). Moreover, no signs of toxic side effects analyzed by blood parameter changes were observed after 3 weeks of administration although a high dose (200 mg/kg) of GEM-ANPs were used. Additionally, in PANC-1-induced tumor mice, intravenous injection of 406-nm GEM-ANPs also could effectively reduce the tumor volume by comparison with free gemcitabine. With these findings, albumin nanosphere-loading approach might be efficacious to improve the antitumor activity of gemcitabine, and the efficacy is associated with the size of GEM-ANPs.
Highlights
Chemotherapy is an important method of adjuvant therapy for pancreatic cancer
Cytotoxicity of GEM-ANPs on human pancreatic carcinoma (PANC-1) cells in vitro Figure 1 shows the inhibition rates of ANPs, gemcitabine, 110-nm GEM-ANPs, and 406-nm GEM-ANPs on the metabolism of PANC-1 cells measured by the MTT method, which is associated with the function of the mitochondria
The inhibition effect of gemcitabine, 110-nm GEM-ANPs, and 406-nm gemcitabine-loaded albumin nanosphere (GEMANP) on PANC-1 cells increases with the increase of concentration and the prolongation of the exposure time
Summary
Chemotherapy is an important method of adjuvant therapy for pancreatic cancer. Gemcitabine, 20,20-difluoro-20deoxycytidine, remains the standard of use and has more significant clinical benefit than fluorouracil (5-FU) (clinical benefit response, 23.8% of gemcitabine treated patients vs. 4.8% of 5-FU-treated patients, p = 0.0022) [1,2]. Of the various formulations available, nanospheres with a mean diameter of 10 to 1,000 nm are widely used as carriers in drug delivery systems in clinical applications [6,7]. They have some potential chemotherapeutic advantages for the treatment of tumors, including pancreatic cancer. They can be biodegradable after intravenous injection. The nanospheres loaded with drugs could be targeted to tumor, the liver, or spleen [11]
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