The implementation of liposome delivery systems ensures the intravenous introduction of hydrophobic photosensitizers used in the treatment of tumors by the photodynamic therapy method with their preservation in a therapeutically effective nonaggregated form and high accumulation selectivity in the tumor. Phthalocyanines are one of the fastest growing classes of antineoplastic photosensitizers, most of which are hydrophobic compounds. In this study the authors have developed the unique composition and technology of preparing the lyophilized liposomal formulation of infrared photosensitizer: aluminum hydroxide tetra-3phenylthiophtalocyanine (Thiosens). At the stage of biological experiments on model mouse tumors, the preservation of high accumulation selectivity in the tumor (selectivity index is higher than 4) and antineoplastic effectiveness (inhibition of tumor growth is from 70 to 94%) were found during the transition from the previously studied model dosage form to the created lyophilized liposomal one. To estimate chemical and pharmaceutical criteria and the photodynamic efficiency of the photosensitizer on a number of transplanted mice tumor models in vivo, we have conducted a preclinical study which has demonstrated the stability of antitumor activity and quality consistency of the developed dosage form for one and a half years.
7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG. It was demonstrated that 7-MG does not induce mutations or structural chromosomal abnormalities, and has no blastomogenic activity. A treatment regimen with 7-MG has been established in mice (50 mg/kg per os, 3 times per week), exerting no adverse effects or changes in morphology. Preliminary data on the 7-MG anticancer activity obtained on transplantable tumor models support our conclusions that 7-MG can become a promising new component of chemotherapy.
In accordance with Russian Federal program of import substitution of foreign medicines quality of Russian drugs in the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, played vincristine-RONC (VC-RONC), which as a drug – the generic’s passed preclinical pharmacological and toxicological testing in comparison with foreign firms vincristine Teva of Israel (VC-Teva). The aim. The aim of present study was the comparative pathomorphological evaluation of the effect of VC-RONC and VC-Teva on the internal organs of rats. Materials and methods. Used 50 weinbrenner male rats, at 10 rats per group. VC-RONC and VC-Teva rats were administered intravenously 3 times daily at aquatoxicity total dose corresponding to the MTD and 1/2 MTD. Control rats in the same regime intravenously administered of 0,9 % sodium chloride solution. Rats were deduced from the experience of 3 and 30 days after the end of administration of the drugs. Conducted macroscopic and histological examination of internal organs by conventional methods, including fixation of the material in 10 % formalin and coloring sections with hematoxylin and eosin. The micropreparations of the internal organs was analyzed under light microscope at magnifications of 100, 400, 1000. Results. VC-RONC, as VC-Teva in cumulative doses of 0,5 and 0,25 mg/kg in 3 days after the end of introductions in the internal organs of rats cause similar slightly pronounced morphological changes: hypoplasia in the bone marrow and spleen, destructive changes in the testes, focal degenerative changes in the kidney and liver of individual rats. On the 30th day after the application of both drugs, some rats regardless of the dose occurred similar symptoms residual morphological changes in the bone marrow, testes, kidneys and liver. Conclusion. Based on the results of macroscopic and histological examination the conclusion about the similarity of the influence of VC-RONC and VC-Teva on the internal organs of rats was made.
The paper presents the results of the study of «acute» toxicity and some results of the study of «subchronic» toxicity of Ormustin, a new anticancer drug belonging to nitrosourea class, in small laboratory animals. In the experiments the laboratory animals - hybrid mice (C57Bl/6J×DBA/2)F1 male and female and outbred male and female rats have been used. On the results of study has been obtained the calculated toxic doses of Ormustin at intravenous administration of the drug in mice and rats; has been given the preliminary assessment of the impact of Ormustin on organs and systems of rats at multiple intravenous administration.
Objective Study of embryotoxicity, teratogenicity and reproductive toxicity of the new drug Lipophtalocyan in rats. Material and Methods Studies were conducted on 210 non-inbred female rats and 105 non-inbred male rats. The drug was administered daily via i. v. injection for 48 days (males) and for 15 days (females) in 2 total doses corresponding to the therapeutic dose (TD) for mice when converted to rats and 10 TD. Results and Conclusion When mating with intact female rats, no changes in sexual behavior were observed, but the index of the ability to fertilize and conceive decreased when compared to the values of the control group by 35–40% (TD index=60%) and by 75–80% (10 TD index=20%). The index of the ability to fertilize and conceive differed from the values of the control group by 90% (TD index=5%) and by 15% (10 TD index=80%). There were no differences in the indicator of embryotoxicity and teratogenicity in intact and drug-treated female rats, compared with the control group. Lipophtalocyan has a negative effect on the male and female reproductive function in rats and has an embryotoxic effect according to the index of the ability to fertilize and conceive, as well as the indices of preimplantation and post-implantation fetal death. The drug does not have a teratogenic effect, neither it affects the physical development of offspring or the rate of maturation of sensory-motor reflexes during feeding.
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