A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system
JOURNAL OF ORTHOPAEDIC RESEARCH
Authors: Kanda, Yutaro; Kakutani, Kenichiro; Yurube, Takashi; Zhang, Zhongying; Miyazaki, Shingo; Kakiuchi, Yuji; Takeoka, Yoshiki; Tsujimoto, Ryu; Miyazaki, Kunihiko; Kawamoto, Teruya; Takada, Toru; Hoshino, Yuichi; Tabata, Yasuhiko; Kuroda, Ryosuke
Abstract
Management of bone metastasis is becoming increasingly important. Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM-CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM-CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA-MB-231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. In vivo, local administration of GM-CDDP (2 mg/kg) significantly suppressed tumor growth and bone osteolysis compared with the control, and local and systemic administration of free CDDP (2 mg/kg; p < 0.05). Local administration of GM-CDDP significantly reduced loss of body weight and elevation of blood urea nitrogen compared with the systemic administration of free CDDP (p < .05). The current study suggests that local administration of GM-CDDP achieves higher antitumor effects with a potential for lesser side effects compared with local or systemic administration of free CDDP.
Investigating of Antioxidant Protective Effects of Shrimp Shells Extracted Chitosan in Broiler Chickens
POULTRY SCIENCE JOURNAL
Authors: Koochacksaraei, Rezaei R.; Dastar, B.; Samadi, F.; Ebrahimi, P.
Abstract
Chitin is the most abundant natural biopolymer that can be converted to chitosan, which has various biomedical applications. This study was conducted to investigate the antioxidant activity of chitosan extracted from shrimp shells on body weight of broiler chickens. The study comprised three experiments. In experiment 1, shrimp (Penaeus merguiensis) shells were demineralized using HCL (1N), deproteinized using NaOH (1N), decolorized using acetone, and deacetylated using 50% NaOH. The antioxidant potencies of chitosan and vitamin C were compared by their abilities to scavenge 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. The DPPH free radical scavenging activity of chitosan at varying concentrations (1-20 mg/ml) ranged between 34.59 and 87.11%, whereas that of 1 mg/ml of vitamin C was 91.1%. In experiment 2, six dietary treatments containing varying concentrations of chitosan (0, 0.125, 0.25, 0.5, 1, and 2 g/kg) were allocated randomly to 60 male broiler chicks from 10 to 42 days of age. Chitosan at varying concentrations had no significant effect on the body weight, but it significantly decreased the MDA level in breast meat (p<0.05). In experiment 3, a total of 20 male broiler chickens were divided into two groups (n=10) and were fed a corn-soybean basal diet with or without chitosan for 42 days. On days 35 and 38, five chickens from each group were treated with carbon tetrachloride (CCL4) at 1 mL/kg body weight to induce oxidative stress. Administration of CCL4 significantly decreased body weight and increased AST and ALT activities, which are indicators of liver damage, on day 42, whereas chitosan improved and normalized body weight and enzyme activity (p<0.05). The results suggested that chitosan extracted from shrimp shells exhibits antioxidant effects by increasing the shelf life of the meat and normalizing the body weight of the broilers as well as serum AST and ALT enzyme activities.