Biodistribution analysis of cisplatin in liposomal form in animals with cisplatinresistant and cisplatin-sensitive carcinoma

Aim: To analyze the relation between pharmacokinetics of cisplatin in liposomal form and antitumor efficacy toward cisplatinresistant and cisplatin-sensitive variants of Guerin carcinoma. Concentration of platinum was measured by atomic absorption spectrophotometry (С115М1 “Selmi”, Ukraine). Elimination constant was calculated based on the dynamics of cisplatin concentration in time period between 1 h to 24 h using nonlinear regression analysis. Area under curve (AUC24) was calculated by the trapezium method. Results: It was shown that for liposomal form of cisplatin (LCp) AUC24 in tumor practically didn’t depend on the level of the tumor sensitivity, while in animals with the resistant variant (CpRGC), AUC24 for free cisplatin (FCp) decreased by 70% less (p < 0.001) as compared to the sensitive tumor strain (CpSGC). Significant decrease of elimination constant of LCp compared to FCp in blood serum of rats bearing either CpRGC or CpSGC tumors favors cisplatin accumulation in tumor tissues with low vascularization level. The dynamics of cisplatin concentration in CpRGC variant was characterized by 90% higher level in 24 h after administration of LCp as compared to FCp (p < 0.05). This fact may explain increased antitumor efficacy of LCp compared to FCp toward CpRGC variant. In the study of kidney function, AUC24 index for LCp was by 68.6% (p < 0.01) and 50.7% (p < 0.05) lower than AUC24 index for FCp in rats with CpRGC and CpSGC variants, respectively. No significant differences have been found in biodistribution of cisplatin in both pharmaceutical forms in liver and lung in CpRGC-r CpSGC-bearing rats. Conclusion: The results suggest that cisplatin in liposomal form possesses higher specificity of antitumor action than free cisplatin

The use of nanoferromagnetics to increase the cytotoxic effect of antitumor drugs

Aim: To investigate the influence of ferromagnetic nanoparticles on antitumor effect of doxorubicin and mitochondria oxidative phosphorylation. Methods: The study was carried out on the mice-hybrids (C57Bl/6xDBA/2) with intraperitoneally (i/p) transplantated Ehrlich ascitic carcinoma. Single i/p injection of doxorubicin (Dox), stabilized ferromagnetic nanoparticles (Fe3O4; 20–40 nm; FM) or their combination were performed 7 days after tumor transplantation. The cytotoxic effect of agents, morphology and cell cycle of tumor cells were studied 24, 48 and 72 h after Dox administration. Results: The investigations showed that ferromagnetic nanoparticles increased the cytotoxic effect of doxorubicin on Ehrlich ascіtic carcinoma mainly 48 h after agents’ administration. The largest number of apoptotic cells was observed in group of animals in which doxorubicin was administered before ferromagnetic nanoparticles. Moreover, the ferromagnetic nanoparticles at concentration 1.45 μg Fe/ml and, particularly, 7.25 μg Fe/ml decreased mitochondria oxygen consumption in phosphorylation state that may negatively influence their living capability. Conclusions: Obtained data point out the perspective of use of certain sized FM nanoparticles to increase the cytotoixc effect of antitumor drugs

Teste de lixiviação de potássio para avaliação do vigor de sementes de soja [Glycine max (L.)Merril] Potassium leaching test for the evaluation of soybean seed vigour

O presente trabalho teve como objetivo principal investigar a possibilidade de se obter indicações rápidas sobre a qualidade fisiológica de sementes de soja através do teste de lixiviação de potássio, cuja eficiência foi avaliada comparativamente as informações fornecidas por outros métodos considerados adequados para a determinação do vigor. Para tanto, utilizou-se quatro lotes de sementes de soja dos cultivares IAC-8 e IAC-15 que foram submetidos aos testes de germinação, primeira contagem de germinação, envelhecimento artificial, condutividade elétrica e determinação do grau de umidade. Além destes foram conduzidos estudos de lixiviação de potássio utilizando-se amostras de sementes não danificadas e de sementes fisicamente puras. A quantidade de potássio lixiviado foi avaliada em fotômetro de chama após 60, 90, 120 e 150 minutos de embebição a 30ºC. As avaliações feitas aos 60, 90 e 120 minutos mostraram-se adequadas para a identificação de lotes com diferentes níveis de vigor, constituindo-se em um método simples e rápido para a avaliação da qualidade fisiológica das sementes.<br>This work was performed to investigate the possibilities of providing rapid indications on the physiological quality of seeds through the potassium leaching test. Four lots of soybean (Glycine max (L.) Merrill) seeds, cultivars IAC-8 and IAC-15 were submitted to germination, first count, accelerated aging, electrical conductivity and seed moisture tests. In addition, studies on potassium leaching were conducted with samples of selected non damaged seeds and with pure seeds. The amount of leached potassium was evaluated in a flame photometer after a 60, 90, 120 and 150 minute imbibition at 30&deg;C. The evaluations after 60, 90 and 120 minutes were suitable for the identification of lots with different levels of vigour, thus proving to be a simple and rapid method for seed vigour evaluation