Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
Right after the detection of MTD, the mice had been sacrificed, and the Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model big inner organs (ie, coronary heart, liver, spleen, lung, and kidney) ended up gathered and weighted. The organ indices Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model had been calculated by the fat ratios of organs (mg) and total entire body (g). More interestingly, the accumulation of NG/DOX obviously downregulated to 0.8-fold and 0.6-fold in kidney and 0.9-fold and 0.7-fold in liver at the DOX·HCl doses of 3.0 mg (kg BW)−1 and 6.0 mg (kg BW)−1, respectively, in comparison with that of free DOX·HCl (P<0.001). The above data indicated that NG/DOX exhibited the enhanced intratumoral accumulation and decreased metabolism at normal organs as compared with free DOX·HCl, which might mean the high antitumor efficacy and security in vivo.
In vivo evaluation of antitumor efficacy
Generally, the efficacy and security of chemotherapy are a contradiction, that is, a higher antitumor efficacy often associates with more serious side effects.29,30 Therefore, the efficacy and security in vivo are the two most critical performances of antitumor drug formulations. The two aforementioned properties of any newly developed formulations should be systematically assessed before clinical application.
The detections of tumor inhibition efficacies toward tumor-xenografted mouse models are a generic approach to judge the antitumor capabilities of nanoscale drug delivery systems.31,32 In this work, the excellent antitumor efficacy of NG/DOX was revealed against H22 hepatoma-bearing BALB/c mouse models. In practice, the tumor volumes were real-time monitored in the process of treatment, and the histopathological and immunohistochemical assessments of tumor tissue sections after treatments were subsequently performed. As soon as the tumor volume grew up to approximately 400 mm3, the treatment of NS as control or free DOX·HCl or NG/DOX with 3.0 mg or 6.0 mg DOX·HCl equivalent per kg body weight was initiated by IV injection for four times every 5 days. The doses of DOX were chosen based on the MTD of free DOX·HCl (~6.0 mg [kg BW]−1) in order to ensure the survival of mice and good treatment efficacy. The tumor volumes were detected daily from the second day after inoculation, which was defined as Day 1. The first treatment was performed on Day 7. As shown in Figure 5, no significant difference in the tumor volumes was observed for all the test groups before Day 11 (P>.05). From Day 11, the distinctions between the antitumor efficacies of all teams had been noticed. The tumors of control group grew out of regulate, and their average volume elevated a few times and achieved t~three,500 mm3 in the subsequent two weeks. The tumors have been suppressed to different extents by means of the solutions with different DOX formulations. In element, the tumor of DOX/3. group grew gradually, while NG/DOX/three. inhibited tumor at a constant volume with the identical dosage of 3. mg (kg BW)−1. Additionally, the greater dosage from 3. mg (kg BW)−1 to 6. mg (kg BW)−1 induced the improved antitumor efficacy.