Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

Characterization and identification of ascorbyl methylsilanol pectinate for cosmetic formulations application

The ascorbyl methylsilanol pectinate (AMP) presents the same functional properties of ascorbic acid (AA). Besides antioxidant and depigmentant activity, the AMP presents silanol in its chemical structure. The aim of this work was to characterize and indentify the AMP alone and in cosmetic formulations. The following techniques were employed: Fourier Transform Infrared Spectrophotometry, particle size distributions, in vitro antioxidant activity with 2.2-diphenyl-1-picrylhydrazyl (DPPH) and Oxigen Radical Absorbance Capacity Assay and High Performace Liquid Chromatography (HPLC) (developed and validated method) for the active ingredient; Microscopy, HPLC and Normal Stability Assay (NSA) for the emulsions. Particle size distributions results showed that the average size of AMP was 1.0 µm and polydispersity index was 0.1. In DPPH assay AA and AMP were statistically the same. The value of ORAC obtained for AMP was 0.74 and for AA in the literature was 0.95. In the NSA the formulations were stable in conditions of 5.0 and 45.0 ± 2.0 ºC for 90 days. Adequate stability at ambient temperature out of reach of light was also observed. Thus, this works presented an acceptable method for quantification of AMP alone and in cosmetic formulations. AMP was an adequate choice for the incorporation in emulsions with antioxidant efficacy.

Antitumor efficacy of EDTA co-treatment with cisplatin in tumor-bearing mice

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na+, K+ and Ca2+). The results showed that the i.p LD50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.

Avaliação imunológica promovida pelo consumo de kombucha em camundongos diabéticos / Immunologic evaluation promoted by the consumption of kombucha in diabetic mice

O kombucha é uma bebida fermentada tradicional, originária da China, preparada pela fermentação de chá preto adoçado com cultura mista de bactérias e leveduras chamada Simbiotic Culture of Bacteria and Yeast (SCOBY). Tem sido alegado que o mesmo possui propriedades funcionais, tais como recuperação ou manutenção de peso corporal, atividade antihiperglicêmica, entre outras. Por não existirem estudos suficientes que as comprovem, este trabalho teve por objetivo avaliar a influência do consumo de kombucha como tratamento alternativo para amenizar e/ou retardar sintomas e complicações do Diabetes Mellitus e identificar as possíveis modificações metabólicas, morfológicas e imunológicas ocorridas em camundongos com diabetes tipo 1. De acordo com os resultados obtidos, observou-se que, apesar de ter havido recuperação de massa corpórea próxima daquela que se tinha antes da indução da diabetes, esse efeito não foi exclusivo do kombucha e, embora a influência no controle glicêmico tenha sido maior nos camundongos normoglicêmicos que diabéticos, acredita-se que a administração por um período prolongado pudesse indicar melhores resultados, uma vez que as avaliações histológicas e morfométricas do intestino demonstraram resultados satisfatórios quanto ao aumento da superfície de mucosa e diminuição do infiltrado inflamatório, favorecendo a modulação imunológica. Logo, considera-se necessária a realização de mais trabalhos para comprovação da capacidade funcional do kombucha e elucidação de sua eficácia enquanto tratamento exclusivo e/ou complementar do diabetes

Kombucha is a traditional Chinese fermented beverage prepared by fermenting sweetened black tea with mixed bacterial and yeast culture called Simbiotic Culture of Bacteria and Yeast (SCOBY). It has been claimed that it has functional properties such as body weight recovery or maintenance, antihyperglycemic activity, among others. Because there are not enough studies to prove them, this study aimed to evaluate the influence of kombucha consumption as an alternative treatment to alleviate and/or delay symptoms and complications of Diabetes Mellitus and to identify possible metabolic, morphological and immunological changes in mice with type 1 diabetes. According to the results obtained, it was observed that, although there was a recovery of body mass close to the one obtained before diabetes induction, this effect was not unique to kombucha, and although the influence on glycemic control was greater in normoglycemic rather than diabetic mice, it is believed that administration over a prolonged period could indicate better results, since histological and morphometric evaluations of the intestine showed satisfactory results in terms of mucosal surface enlargement and decreased inflammatory infiltrate, favoring immune modulation. . Therefore, further work is considered necessary to prove the functional capacity of kombucha and to elucidate its effectiveness as an exclusive and / or complementary treatment of diabetes

A nanoemulsion-based delivery system for imatinib and in vitro anticancer efficacy

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients' whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Efficacy and safety of cumaru syrup as complementary therapy in mild persistent asthma: a double-blind, randomized, placebo-controlled study

Amburana cearensis is a medicinal plant known as "cumaru". It is used in Northeast Brazil in the treatment of respiratory diseases. This was a randomized, double-blind, placebo-controlled study, with the aim of evaluating the efficacy and safety of cumaru syrup as complementary therapy in mild persistent asthma. The study consisted of 3 phases, pre-treatment, treatment and post-treatment. The primary efficacy outcome was comparison of the changes reported by patients of the cumaru and placebo groups after treatment, using the "Asthma Quality of Life Questionnaire" (AQLQ). The secondary outcome was the effect of cumaru syrup on lung function based on spirometry. The results showed that in the cumaru group, the proportion of patients who had global improvement in asthma symptoms was significantly greater (61.90%, P=0.0009) than in the placebo group (9.52%). Only the spirometric parameters Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1) showed significant intergroup differences in post-treatment (P<0.05). The hematological and serum chemistry tests performed in the pre-treatment and post-treatment showed no statistically significant differences (P>0.05). Adverse events were reported by 3 patients (14.29%) in the cumaru group and 3 patients (14.29%) in the placebo group. All adverse events were considered non-serious and mild.

Amburana cearensis é uma planta medicinal conhecida como "cumaru". No Nordeste do Brasil é usada no tratamento de doenças respiratórias. Este é um estudo randomizado, duplo-cego e controlado por placebo, com o objetivo de avaliar a eficácia e segurança do xarope de cumaru como terapia complementar da asma persistente leve. O estudo consistiu de três fases, pré-tratamento, tratamento e pós-tratamento. A variável primária para determinação da eficácia foi a comparação das mudanças referidas pelos pacientes dos grupos cumaru e placebo após o tratamento, usando o "Questionário sobre Qualidade de Vida na Asma" (QQVA). A variável secundária foi o efeito do xarope de cumaru na função pulmonar baseado na espirometria. Os resultados mostraram que no grupo cumaru, a proporção de pacientes com melhora global dos sintomas da asma foi significativamente maior (61,90%, P=0.0009) que no grupo placebo (9,52%). Somente os parâmetros espirométricos, capacidade vital forçada (CVF) e volume expiratório forçado no primeiro segundo (VEF1), mostraram diferença intergrupo significtivas no pós-tratamento (P<0.05). Os testes hematológicos e do soro realizados no pré-tratamento e pós-tratamento não mostraram diferenças estatisticamente significativas (P>0.05). Eventos adversos foram reportados por 3 pacientes (14,29%) no grupo cumaru e 3 (14,29%) no grupo placebo. Todos os eventos adversos foram não sérios e leves.