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The most studied phyto constituent isolated from Virola surinamensis (Rol. ex Rottb.) Warb., Myristicaceae, is the tetrahydrofuran neolignan grandisin, which exhibits a series of biological activities, including trypanocidal, larvicidal and antitumoral. Due to its extremely low solubility, additional studies, including in vivo investigations are challenged by the difficulties in the development of an effective drug delivery system for grandisin. The encapsulation in polymeric nanoparticles is a very attractive alternative for overcoming some of these limitations. In this work, PLGA nanocapsules loaded with grandisin were developed in an attempt to optimize the efficacy of grandisin as an antitumoral drug, with high drug loading and efficiency, prolonged drug release and increased physical-chemical stability. Mean diameter of the nanocapsules was lower than 200 nm, with very low polydispersity. Encapsulation efficiency was above 90%. A sustained in vitro drug release was achieved for up to twenty days and cytotoxicity was markedly increased (IC50 for grandisin-NC and grandisin were 0.005 µM and 0.078 µM, respectively), indicating that polymeric nanocapsules are a potential drug delivery system for grandisin allowing the preparation of formulations viable for further in vivo studies

Nanoparticles containing GEN and PTX with a temporal pattern of drug release indicated that the combined effect of cytotoxic and antiangiogenic drugs present in the formulation contributed to the overall enhanced antitumor activity of the nanomedicine.

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This study investigated the chemoprotective effects of Punica granatum L. (Punicaceae) fruits alcoholic extract (PGE) on mice exposed to hexavalent chromium [Cr(VI)]. Animals were pretreated with PGE (25, 50 or 75 mg/kg/day) for 10 days and subsequently exposed to a sub-lethal dose of Cr(VI) (30 mg/kg). The frequency of micronucleated polychromatic erythrocytes in the bone marrow was investigated and the Cr(VI) levels were measured in the kidneys, liver and plasm. For the survival analysis, mice were previously treated with PGE for 10 days and exposed to a single lethal dose of Cr(VI) (50 mg/kg). Exposure to a sub-lethal dose of Cr(VI) induced a significant increase in the frequency of micronucleated cells. However, the prophylactic treatment with PGE led to a reduction of 44.5% (25 mg/kg), 86.3% (50 mg/kg) and 64.2% (75 mg/kg) in the incidence of micronuclei. In addition, the 50 mg/kg dose of PGE produced a higher chemoprotective effect, since the survival rate was 90%, when compared to that of the non-treated group. In these animals, reduced amounts of chromium were detected in the biological materials, in comparison with the other groups. Taken together, the results demonstrated that PGE exerts a protective effect against Cr(VI)-induced genotoxicity. Uniterms INTRODUCTIONChromium occurs naturally in the environment in different oxidation states, where Cr(III) and Cr(VI) are the most prevalent. The hexavalent form is usually linked with oxygen and is a strong oxidizing agent. Studies have shown that Cr(VI) is a mutagenic, carcinogenic and teratogenic agent, which easily penetrates the cell membrane in the form of chromate anion (Barceloux, 1999;Acharya et al., 2006;Nickens et al., 2010;Chang et al., 2011;Okello et al., 2012). Its molecular mechanisms of toxicity are not yet fully known, but it is believed that the intracellular increase in the production of reactive oxygen species (ROS) is probably a key factor in inducing cell damage (Ye et al., 1999;Wu et al., 2012). These reactive species can cause damage to macromolecules such as DNA, proteins and lipids, thereby inhibiting their functions (Valko et al., 2007;Yan et al., 2012) and may even trigger apoptotic cell death (Liu, Chen, 2006;Liu et al., 2008).Cr(VI) has been widely used in metallurgical, refractory and chemical industries. It has been considered a potent occupational carcinogen among workers involved in electrodeposition, metal finishes/welding, wood preservatives, organic synthesis procedures and in leather tanning (Barceloux, 1999;Shrivastava et al., 2002;Acharya et al., 2006;Nickens et al., 2010). In such activities occupational exposure to Cr(VI)-contaminated dust and aerosols occurs predominantly through inhalation or skin contact (Zagrodzki et al., 2007). Non-occupational exposure to Cr(VI) can also occur through cigarette smoke, automobile emissions and the inappropriate disposal of chromium-containing waste in the environment (O'Brien et al., 2003;Russo et al., 2005).The literature has shown that the administration of antioxidant agents ...

The results demonstrated that grandisin induced in-vitro cytotoxicity and antiangiogenic effects in mice while it acted against tumour evolution, prolonging host survival.

The results demonstrated that grandisin induced in-vitro cytotoxicity and antiangiogenic effects in mice while it acted against tumour evolution, prolonging host survival.

A new molecule, LQFM048, originally designed through molecular hybridization using green chemistry approach, is in development as a photoprotective agent. Eye irritation, skin toxicity and genotoxicity evaluations are mandatory for predicting health risks. In this context, the purpose of this study was to investigate the eye irritation potential of LQFM048 by combining Short Time Exposure (STE), Bovine Corneal Opacity and Permeability (BCOP) associated with corneal histomorphometry and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Additionally, skin toxicity was evaluated by interleukin-18 production in the HaCaT keratinocyte, Local Lymph Node Assay (LLNA:BrdU-ELISA) method, 3T3 Neutral red uptake (NRU) assay and in vivo phototoxicity test. Genotoxic potential of LQFM048 was also analyzed by cytokinesis-block micronucleus assay (MNvit test-cytoB) in HepG2 cells. Our results showed that LQFM048 did not induce eye irritation and it was classified as UN GHS No Category for both STE and BCOP assays and non-irritating for HET-CAM test. LQFM048 showed non-potential skin sensitization with stimulation index (SI=0.7) in the LLNA:BrdU-ELISA method. Corroborating in vivo tests, it did not promote significant cytotoxicity in HaCaT cells and it showed similar levels of IL-18 when compared to control. Furthermore, LQFM048 induced non-phototoxic potential with photo-irritation factor (PIF) and mean photo effect (MPE) of 1 and -0.138, respectively, for 3T3 cells. Similarly, it was not phototoxic for in vivo testing with or without exposure to UVA, showing SI values of 1 and 1.2, respectively. The micronucleus test showed that LQFM048 was not genotoxic, under the conditions tested.In conclusion, LQFM048, a heterocyclic compound obtained through an environmentally acceptable simple synthetic route, seems to be safe for human use, especially for the development of a new sunscreen product, since it is neither an eye irritant, nor a contact allergen, nor mutagenic and nor phototoxic.