ABSTRACT
The aim of this study was the encapsulation of trans-dehydrocrotonin (t-DCTN) and its inclusion complexes with hydropropyl-beta-cyclodextrin (HP-beta-CD) in liposomes to improve t-DCTN antitumor activity. The in vitro kinetic profiles of t-DCTN-loaded liposomes (LD) and t-DCTN:HP-beta-CD-loaded liposomes (LC) were evaluated using the dialysis technique. The antitumor activity of LD and LC were investigated against Sarcoma 180 in Swiss mice. Histopathological and hematological analyses were carried out. The amounts of t-DCTN and t-DCTN:HP-beta-CD inclusion complex encapsulated in liposomes were equivalent to 1 mg of t-DCTN. The encapsulation efficiencies of LD and LC were 95.0 +/- 3.8% and 91.1 +/- 5.6%, respectively. In relation to kinetics, the drug release profiles of t-DCTN are in substantial agreement with the Fickian model. The treatment of animals with LD and LC produced tumor inhibitions of 79.4 +/- 9.6% and 63.5 +/- 5.5%, respectively. The liposomal encapsulation of t-DCTN by entrapment in the phospholipid bilayer increased at twice the antitumor activity. Moreover, the liposomal formulations reduced the hepatotoxicity effect of the drug and no significant hematological toxicity was observed in the treated animals. However, the counting of platelets was slightly decreased. Thus, the results show that the development of liposomal formulations containing t-DCTN or t-DCTN:HP-beta-CD is an important advance for enabling this drug to be use in therapy.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Diterpenes, Clerodane/administration & dosage , Diterpenes, Clerodane/pharmacology , 2-Hydroxypropyl-beta-cyclodextrin , Animals , Antineoplastic Agents/chemistry , Chemistry, Pharmaceutical , Diterpenes, Clerodane/chemistry , Diterpenes, Clerodane/therapeutic use , Kinetics , Liposomes , Liver/drug effects , Liver/pathology , Male , Mice , Particle Size , Regression Analysis , Sarcoma/blood , Sarcoma/drug therapy , Sarcoma/pathology , Static Electricity , beta-Cyclodextrins/chemistryABSTRACT
The use of plants for the treatment of diseases continues to rise although there are few studies providing proof of these effects. One of these plants is the Anacardium occidentale, popularly known as the cashew. The present study evaluated the possible genotoxic and protective activities of cashew stem bark methanolic extract, in vitro, using methyl methanesulfonate (MMS) as a positive control, to compare possible mechanisms of DNA damage induction in the Comet assay. The antigenotoxicity protocols used were pre, simultaneous and post-treatment in relation to MMS. In genotoxicity and antigenotoxicity assessments, besides MMS, PBS was used as the negative control and three concentrations of the A. occidentale extract (500 microg/mL, 1000 microg/mL and 2000 microg/mL) were used on Chinese hamster lung fibroblasts (V79 cells). The Comet assay revealed that the two lowest concentrations tested presented no genotoxic activity, whereas the highest presented genotoxicity. All of the concentrations showed protective activity in simultaneous and post-treatment in relation to MMS. Further studies are required to identify the substances that comprise the extract and more clearly comprehend the antigenotoxic mechanism detected in this study.
Subject(s)
Anacardium/chemistry , DNA Damage/drug effects , Plant Extracts/pharmacology , Animals , Cell Line , Comet Assay , Cricetinae , Methyl Methanesulfonate/toxicity , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Stems/chemistryABSTRACT
The crude leaf extracts of Croton cajucara Benth. were studied for their antinociceptive property in chemical and thermal models of nociception in mice. All the tested extracts (hexanic, chloroformic and methanolic), at oral doses of 100 and 200 mg/kg demonstrated significant inhibition of acetic acid-induced writhing and the second phase response of formalin, but did not manifest a significant effect in hot-plate test.
