Croton argenteus preparation inhibits initial growth, mitochondrial respiration and increase the oxidative stress from Senna occidentalis seedlings.

Senna ocidentalis is a weed, native to Brazil, considered to infest crops and plantations, and is responsible for yield losses of several crops, particularly soybean. The aim of this work was to evaluate if the Croton argenteus extract and fractions possess phytotoxic activity on S. ocidentalis. The crude ethanolic extract (CEE) and its hexanic (HF), chloroformic (CLF) and ethyl acetate (EAF) fractions were tested in germination, growth, oxidative stress increase, Adenosine triphosphate, L-malate and succinate synthesis. The crude extract and its fractions slowed down the germination of S. ocidentalis and decreased the final percentage of germination. Oxidative stress was also increased in the seedlings, by an increase of catalase, peroxidase, superoxide dismutase, glutathione reductase and lipid peroxidation; and it became clear that the ethyl acetate fraction was more phytotoxic. The results indicate that the crude extract and fractions of C. argenteus compromise the mitochondrial energy metabolism, by the inhibition of mitochondrial ATP production, with a decrease in the production of L-malate and succinate. The ethyl acetate fraction of C. argenteus showed high activity on germination and growth, and these effects take place by means of mitochondrial metabolism alterations and increase the oxidative stress, leading the seedling death.

Risedronate-loaded Eudragit S100 microparticles formulated into tablets.

Risedronate, an anti-osteoporotic drug, is associated with low patient compliance due to the upper gastrointestinal side-effects and stringent dosing regimes. This study aimed to prepare and characterize risedronate-loaded Eudragit® S100 microparticles and develop a final dosage form by the compression of microparticles using direct tableting excipients. Microparticles were prepared by spray-drying and presented yield of 54%, encapsulation efficiency higher than 90%, mean diameter of 3.3 µm, moisture content around 8% and exhibited spherical shape and poor flowability. At pH 1.2, 23% of risedronate was released from microparticles in 120 min, while at pH 6.8 the drug took 90 min to reach 99.5%. Microparticles were compressed into tablets using microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide and 2 polyvinylpyrrolidone concentrations (5% and 15%). Tablets presented low variations in weight, thickness and drug content. Besides, the formulations showed sufficient hardness, low friability and disintegrated in less than 15 min. In acid medium, no more than 16% of the drug was released in 120 min, while in intestinal medium the formulations prolonged the risedronate release for 240 min. Finally, the developed tableted microparticles can be considered a promising dosage form for oral risedronate administration.

Influence of the type of vegetable oil on the drug release profile from lipid-core nanocapsules and in vivo genotoxicity study.

The use of rice bran (RB), soybean (SB) or sunflower seed (SF) oils to prepare lipid-core nanocapsules (LNCs) as controlled drug delivery systems was investigated. LNCs were prepared by interfacial deposition using the preformed polymer method. All formulations showed negative zeta potential and adequate nanotechnological characteristics (particle size 220-230 nm, polydispersity index < 0.20). The environmental safety was evaluated through an in vivo protocol (Allium cepa test) and LNCs containing RB, SB or SF oils did not present genotoxic potential. Clobetasol propionate (CP) was selected as a model drug to evaluate the influence of the type of vegetable oil on the control of the drug release from LNCs. Biphasic drug release profiles were observed for all formulations. After 168 h, the concentration of drug released from the formulation containing SF oil was lower (0.36 mg/mL) than from formulations containing SB (0.40 mg/mL) or RB oil (0.45 mg/mL). Good correlations between the consistency indices for the LNC cores and the burst and sustained drug release rate constants were obtained. Therefore, the type of the vegetal oil was shown as an important factor governing the control of drug release from LNCs.

Enhancement of tioconazole ungual delivery: Combining nanocapsule formulation and nail poration approaches.

This work investigated the impact of formulation including in vitro release profile, repeated dosing, and nail poration on the ex vivo nail delivery performance of antifungal formulations. Chitosan coated and uncoated tioconazole-loaded nanocapsules and a nano-based film-forming vehicle were assessed via in vitro release and in vitro permeation tests using an artificial membrane and human nail clippings, respectively. The later involved single and daily dosing experiments with intact and porated nails. Additional experiments with Nile Red-loaded formulations evaluated the depth of penetration of the fluorescent marker into the nail by laser scanning confocal microscopy. The nanocapsule formulations prolonged release of tioconazole for longer than the control solutions and this ability was related to an enhanced nail penetration of the drug. Further, the new film-forming formulation delivered its drug payload more efficiently than a marketed product. Daily dosing of the formulations doubled the amount of drug recovered from the nails. Porating the nails enhanced tioconazole delivery in single dose experiments only. The depth of penetration of Nile Red into the nails clippings ranged between 90-160 µm. This research suggests that ensuring prolonged release of a drug is fundamental to develop efficacious topical nail formulations.

An innovative polysaccharide nanobased nail formulation for improvement of onychomycosis treatment.

Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL-1), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.

Dithranol-loaded lipid-core nanocapsules improve the photostability and reduce the in vitro irritation potential of this drug.

Dithranol is a very effective drug for the topical treatment of psoriasis. However, it has some adverse effects such as irritation and stain in the skin that make its application and patient adherence to treatment difficult. The aims of this work were to prepare and characterize dithranol-loaded nanocapsules as well as to evaluate the photostability and the irritation potential of these nanocarriers. Lipid-core nanocapsules containing dithranol (0.5 mg/mL) were prepared by interfacial deposition of preformed polymer. EDTA (0.05%) or ascorbic acid (0.02%) was used as antioxidants. After preparation, dithranol-loaded lipid-core nanocapsules showed satisfactory characteristics: drug content close to the theoretical concentration, encapsulation efficiency of about 100%, nanometric mean size (230-250 nm), polydispersity index below 0.25, negative zeta potential, and pH values from 4.3 to 5.6. In the photodegradation study against UVA light, we observed a higher stability of the dithranol-loaded lipid-core nanocapsules comparing to the solution containing the free drug (half-life times around 4 and 1h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing EDTA, respectively; half-life times around 17 and 7h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing ascorbic acid, respectively). Irritation test by HET-CAM method was conducted to evaluate the safety of the formulations. From the results it was found that the nanoencapsulation of the drug decreased its toxicity compared to the effects observed for the free drug.

Homeopathy and biotherapy in Bothrops asper envenomation

Snake envenomation by Bothrops asper is a common problem affecting cattle raising and rural workers in farms across Latin America. Control of hemorrhage must often be ensured at the site of the accident, as medical care and antivenom therapy might not be available on the premises. The aim of the present study was to investigate the effects of homeopathic medicine Phosphorus 6cH, biotherapy Bothrops asper 6cH and a homeopathic formula on hemorrhage induced by B. asper envenomation. Groups of mice received the investigated treatments before and after envenomation (minimal hemorrhagic dose) and the diameter and intensity of hemorrhage were assessed. When administered before envenomation, all 3 treatments reduced the hemorrhage diameter; the best results were achieved with formula administered 14 days before envenomation and Phos 6cH 7 days before. Among the animals treated after envenomation, Phos 6cH in 4 doses/hour exhibited the best results in terms of hemorrhage diameter and intensity. We conclude that both homeopathy and biotherapy exhibit considerable potential as alternative treatment to reduce hemorrhage induced by B. asper venom. (AU)

Acidentes por Bothrops asper afetam frequentemente o gado e trabalhadores rurais em toda a América Latina. Dado que tanto atenção médica quanto tratamento antiofídico podem não estar disponíveis no local do acidente, é necessário controlar a hemorragia in loco. O objetivo do presente estudo foi avaliar os efeitos do medicamento homeopático Phosphorus 6cH, bioterápico Bothrops asper 6cH e um complexo homeopático na hemorragia induzida por B. asper. Diferentes grupos de camundongos receberam os medicamentos testados antes e depois do envenenamento (dose hemorrágica mínima) e foram medidos o diâmetro e a intensidade da hemorragia. Quando administrados antes do envenenamento, os 3 tratamentos reduziram o diâmetro da hemorragia, obtendo-se os melhores resultados com o complexo administrado 14 dias antes e Phos 6cH 7 dias antes. Entre os animais tratados depois do envenamento, os melhores resultados em termos de diâmetro e intensidade da hemorragia foram obtidos com Phos 6cH em 4 doses/hora. Conclui-se que tanto a homeopatia quanto o bioterápico apresentam grande potencial como tratamento alternativo para reduzir a hemorragia induzida por B. asper. (AU)

Homeopathy and biotherapy in Bothrops asper envenomation

Snake envenomation by Bothrops asper is a common problem affecting cattle raising and rural workers in farms across Latin America. Control of hemorrhage must often be ensured at the site of the accident, as medical care and antivenom therapy might not be available on the premises. The aim of the present study was to investigate the effects of homeopathic medicine Phosphorus 6cH, biotherapy Bothrops asper 6cH and a homeopathic formula on hemorrhage induced by B. asper envenomation. Groups of mice received the investigated treatments before and after envenomation (minimal hemorrhagic dose) and the diameter and intensity of hemorrhage were assessed. When administered before envenomation, all 3 treatments reduced the hemorrhage diameter; the best results were achieved with formula administered 14 days before envenomation and Phos 6cH 7 days before. Among the animals treated after envenomation, Phos 6cH in 4 doses/hour exhibited the best results in terms of hemorrhage diameter and intensity. We conclude that both homeopathy and biotherapy exhibit considerable potential as alternative treatment to reduce hemorrhage induced by B. asper venom. (AU)

Acidentes por Bothrops asper afetam frequentemente o gado e trabalhadores rurais em toda a América Latina. Dado que tanto atenção médica quanto tratamento antiofídico podem não estar disponíveis no local do acidente, é necessário controlar a hemorragia in loco. O objetivo do presente estudo foi avaliar os efeitos do medicamento homeopático Phosphorus 6cH, bioterápico Bothrops asper 6cH e um complexo homeopático na hemorragia induzida por B. asper. Diferentes grupos de camundongos receberam os medicamentos testados antes e depois do envenenamento (dose hemorrágica mínima) e foram medidos o diâmetro e a intensidade da hemorragia. Quando administrados antes do envenenamento, os 3 tratamentos reduziram o diâmetro da hemorragia, obtendo-se os melhores resultados com o complexo administrado 14 dias antes e Phos 6cH 7 dias antes. Entre os animais tratados depois do envenamento, os melhores resultados em termos de diâmetro e intensidade da hemorragia foram obtidos com Phos 6cH em 4 doses/hora. Conclui-se que tanto a homeopatia quanto o bioterápico apresentam grande potencial como tratamento alternativo para reduzir a hemorragia induzida por B. asper. (AU)