Caracterização físico-química do potencial agente antineoplásico Beta-lapachona / Physicochemical characterization of the anticancer drug Beta-lapachone

A Beta-lapachona tem inspirado uma série de trabalhos científicos, tendo em vista os inúmeros estudos farmacológicos relatados na literatura, que comprovam suas atividades antibacteriana, antifúngica, antitripanossômica, antiviral, anti-inflamatória e antineoplásica. Devido a sua potente atividade anticancerígena, este fármaco encontra-se, atualmente, em estudo clínico de fase II para o tratamento de câncer pancreático. O objetivo deste estudo foi determinar as propriedades físico-químicas deste ativo com o emprego de diversas ferramentas analíticas, como, difração de Raios X, infravermelho, análises térmicas, microscopia eletrônica de varredura e ensaio de dissolução. Os resultados obtidos na difração de raios X revelaram o padrão policristalino do fármaco; o infravermelho identificou os principais grupos funcionais da Beta-lapachona; os dados das análises térmicas apresentaram características de um produto cristalino e de alta pureza; a eletromicrografia demonstrou sua forma cristalina, como cristais acidulares bem definidos de tamanho regular, corroborando com os dados do difratograma. No estudo de dissolução comprovamos que a Beta-lapachona é praticamente insolúvel em água, sendo necessário o desenvolvimento de estratégias tecnológicas destinadas a melhorar a sua solubilidade em meio aquoso. Dessa forma, a determinação das principais características físico-químicas da Beta-lapachona será extremamente útil na identificação de problemas que possam vir a surgir durante a formulação e auxiliará no desenvolvimento de formas farmacêuticas mais eficazes e com qualidade.

A series of scientific papers on Beta-lapachone has been inspired by the numerous pharmacological reports in the literature that demonstrate its antibacterial, antifungal, antitrypanosomal, antiviral, anticancer and anti-inflammatory activities. Owing to its potent anticancer activity, this drug is currently undergoing phase II clinical trials for the treatment of pancreatic cancer. The aim of this study was to determine the physicochemical properties of this drug by means of several analytical tools, such as X-ray diffraction (XRD), infrared (IR) spectroscopy, thermal analysis, scanning electron microscopy (SEM) and dissolution test. The XRD patterns showed the polycrystalline state of the drug; IR spectroscopy identified the main functional groups of Beta-lapachone; the data from thermal analysis showed characteristics of a crystalline product of high purity and the SEM micrographs showed the crystalline form as well-defined acidulated crystals of regular size, corroborating the XRD patterns. In the dissolution test we found that Beta-lapachone is practically insoluble in water, necessitating the development of technological strategies to improve its solubility in aqueous media. Thus, the determination of the main physicochemical characteristics of Beta-lapachone will be extremely useful in identifying problems that may arise during the design and in the development of more effective and higher quality pharmaceutical forms of this drug.

Portulaca oleracea L. extract ameliorates the cisplatin-induced toxicity in chick embryonic liver.

Cisplatin, a cytotoxic agent used in treating cancer, at high doses induces hepatotoxicity. In this study, we investigated the protective role of aqueous extract of aerial parts of Portulaca oleracea L. (Po) against cisplatin-induced hepatotoxicity in chick embryonic liver. A group of 12 day old chick embryos, acclimatized to laboratory conditions were treated with a single dose of cisplatin (100 µg), while another group received Po extract at different doses (1 and 3 mg) 6 h prior to cisplatin treatment. The biochemical parameters were estimated after 24 and 72 h of incubation. A dose-dependent increase in biochemical parameters, such as alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, malondialdehyde levels and a decrease in antioxidant enzymes levels like superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase and reduced glutathione were observed in cisplatin-treated animals, indicating a definite damage to the liver tissue. Pre-treatment with Po extract was found to provide significant protection against cisplatin-induced hepatotoxicity, as evident by the recovered levels of the altered changes in the measured biochemical parameters.