Lipid reducing potential of liposomes loaded with ethanolic extract of purple pitanga (Eugenia uniflora) administered to Caenorhabditis elegans.

The ethanolic extract obtained from purple pitanga fruit (Eugenia uniflora - PPE) has been previously described by its potential to reduce lipid accumulation in vitro. In this study, we aimed to study this potential in vivo using Caenorhabditis elegans as animal model. Considering the low pH of the extract, its hydrophilic characteristic, its absorption by the medium where the worms are cultivated and the need of a chronic exposure in the worms solid medium, we have loaded liposomes with PPE and investigated its potential for oral administration. Following 48 h exposure to the PPE-loaded liposomes on worms nematode growth medium, we did not observe any toxic effects of the formulation. Under high cholesterol diet, which increased worms total lipid and also triacylglycerides levels, liposomes containing PPE were able to significantly attenuate these alterations, which could not be observed when worms were treated with free PPE. Furthermore, we could evidence that liposomes were ingested by worms through their labelling to uranin fluorescence dye. Through total phenolic compounds quantification, we estimated an entrapment efficacy of PPE into liposomes of 87.7%. The high levels of phenolic compounds present in PPE, as previously described by our group, indicate that these antioxidants may interfere in worms lipid metabolism, which may occur through many and intricated mechanisms. Although the use of conventional liposomes for human consumption may not be pragmatic, its application for oral delivery of a hydrophilic substance in C. elegans was absolutely critical for our experimental design and has proven to be efficient.

Brazilian Consensus Recommendation on the Use of Polymethylmethacrylate Filler in Facial and Corporal Aesthetics.

BACKGROUND: Considering that aesthetic benefits can be obtained with the use of permanent filling materials, this work focuses on the development of a consensus regarding the facial and corporal use of polymethylmethacrylate (PMMA) filler in Brazil. METHODS: A questionnaire regarding PMMA treatment, which included items on the main indication, application site, volume of product applied, criteria for selection of the material, complications, contraindications, and individual professional experience, was distributed to the Expert Group members. In addition, the responses were summarized, constituting the starting point for the debate regarding the use of PMMA-based fillers on The First Brazilian PMMA Symposium to create a guideline to be followed in PMMA facial and corporal treatments. RESULTS: This survey involved 87,371 cases. PMMA treatment is recommended for restorative and aesthetic purposes in facial and corporal cases, particularly for facial balance. PMMA 30% filler is recommended in specific facial sites (nose, mentum, mandible angle, zygomatic arc, and malar). PMMA filler is contraindicated in other sites (lips) regardless of concentration. With regard to facial treatment, the juxtaperiostal is the application plane most recommended. For PMMA corporal application, intramuscular is the application plane most indicated, while intradermal and justadermal planes are contraindicated. The submuscular plane application is relative to PMMA filler concentration. The experts also inquired regarding the amount of PMMA recommended in each corporal site (50 mL in the calf, 100-150 mL in the gluteal region). CONCLUSION: These recommendations provide a guideline for physicians, supporting them to perform safe and efficacious treatment with PMMA fillers. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Optimization of Curcuma Oil/Quinine-Loaded Nanocapsules for Malaria Treatment.

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit® RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 24 factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit® RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78 ± 3.60 and 4.76 ± 3.46% for F9 and F13, respectively) and highest survival mean time (15.3 ± 2.0 and 14.9 ± 5.6 days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.

Clozapine-Loaded Polysorbate-Coated Polymeric Nanocapsules: Physico-Chemical Characterization and Toxicity Evaluation in Caenorhabditis elegans Model.

The aim of this work was to develop and characterize clozapine loaded polysorbate-coated polymeric nanocapsules and assess their toxicity in Caenorhabditis elegans, an invertebrate animal model. Formulations were prepared by nanoprecipitation method and characterized by particle size, zeta potential, pH, drug loading, entrapment efficiency and in vitro drug release. All nanocapsules prepared presented diameter around 140 nm, pH slightly acid and negative zeta potential. In vitro studies showed biphasic drug release from nanocapsules with decreasing of the release rate on nanoencapsulation. The t(1/2)beta of clozapine was 7.23 +/- 0.73 and 2.23 +/- 0.97 h for nanoencapsulated and free drug, respectively (p < 0.05), in pH 1.2 medium. Similar results were obtained in pH 6.8 buffer. Regarding toxicity evaluation, worms exposed to clozapine-loaded nanocapsules did not show the same mortality rate compared to others formulations, as the survival was significantly higher than the free drug treated-group. In addition, we observed that free clozapine decreased egg laying at the first reproductive day, whereas nanoencapsulated clozapine did not depict significant change of this parameter. Longevity assay showed no significant difference, demonstrating that the toxicological effects of clozapine observed in C. elegans are acute. In addition, we proved that free and nanoencapsulated clozapine were orally uptake by the worms, as determined by fluorescein-labeled nanocapsules. Then, the use of nanocapsules delayed the drug release and minimized the toxic effects of clozapine in worms, which can be used as a new animal model to evaluate the nanotoxicity of drug delivery systems.

Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by ß-amyloid1-42 in aged female mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a clinically and progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Some studies showed that chrysin has antioxidant and anti-inflammatory properties. However, your bioavailability is relatively low. Therefore, the present study was designed to investigate the effects of chrysin loaded lipid-core nanocapsules (LNCs) on neurochemical and behavioral changes in a model of AD induced by ß-amyloid1-42 (Aß1-42) peptide in aged female mice. For this purpose, aged female mice received free chrysin (FC) (5 mg/kg, per oral, p.o.) or chrysin loaded LNCs (C1-LNC and C5-LNC) (1 or 5 mg/kg, p.o.) for 14 days after Aß1-42 administration (400 pmol, i.c.v.). Aß1-42 induced significant impairments on memory and learning (morris water maze task, object recognition and step-down-type passive avoidance), also caused oxidative stress, reduced the levels of brain-derived neurotrophic factor (BDNF), increased neuroinflammation in prefrontal cortex and hippocampus of aged animals. Thus, C1-LNC and C5-LNC displayed significant effect against Aß1-42, via attenuation of oxidative stress and neuroinflammation, modulation of neurochemical and behavioral changes in a model of AD. These results point to chrysin loaded LNCs (mainly C5-LNC) can be a promising biomedical tool and a new therapeutic approach for treatment and prevention of AD.

Co-encapsulation of acyclovir and curcumin into microparticles improves the physicochemical characteristics and potentiates in vitro antiviral action: Influence of the polymeric composition.

The present study developed and characterized microparticles formulations containing acyclovir and curcumin co-encapsulated in order to overcome the biopharmaceutical limitations and increase the antiviral effect of both drugs. The microparticles were prepared by a spray drying methodology following the ratio 1:3 (drug:polymer), which were made by hydroxypropylmethylcellulose (HPMC) and/or Eudragit® RS100 (EUD). The MP-1 formulation was composed of HPMC and EUD (1:1), MP-2 formulation was composed only of HPMC and MP-3 formulation was composed only of EUD. All formulations showed yielding around 50% and acceptable powder flowability. Drug content determination around 82.1-96.8% and 81.8-87% for acyclovir and curcumin, respectively. The microparticles had spherical shape, size within 11.5-15.3 µm, unimodal distribution and no chemical interactions among the components of the formulations. Of particular importance, the polymeric composition considerably influenced on the release profile of the drugs. The in vitro release experiment demonstrated that the microencapsulation provided a sustained release of acyclovir as well as increased the solubility of curcumin. Besides, mathematical modeling indicated that the experimental fit biexponential equation. Importantly, drugs microencapsulation promoted superior antiviral effect against BoVH-1 virus in comparison to their free form, which could be attributed to the improvement in the aforementioned physicochemical parameters. Therefore, these formulations could be promising technological drug carriers for acyclovir and curcumin, which highlight the great offering a potential alternative treatment for viral herpes.

Educational Activities for Rural and Urban Students to Prevent Skin Cancer in Rio Grande do Sul, Brazil.

BACKGROUND: Excessive exposure to the sun during childhood is strongly associated with the development of skin cancer in the future. The only way to prevent the development of skin cancer is to protect against ultraviolet radiation, which can be achieved through strategic awareness during childhood and adolescence. OBJECTIVE: The aim of this work was to evaluate the impact of educational activities for rural and urban students to promote the use of sunscreens and prevent skin cancer. MATERIALS AND METHODS: This study was carried out with students (9-12 years) of rural (n=70) and urban (n=70) schools in Rio Grande do Sul state, Brazil. The educational interventions were lectures and games. The impact of this strategy was evaluated through the application of a questionnaire before and after the interventions. RESULTS: Before the intervention, it was found around 50% of rural and urban students were not aware of the damage caused by sun exposure, often exposing themselves to UV radiation without use sunscreen ( ~ 25 %) and at the most critical times of the day/year. After the lectures we observed an improvement in the behavior of the students with regard to sun exposure and knowledge about skin cancer. CONCLUSIONS: The results of this study emphasize the importance of prevention strategies for skin cancer and promoting the use of sunscreens based educational strategies. The interventions were of great value in relation to disseminating knowledge on the subject.

Quinine-Loaded Polymeric Nanoparticles: Validation of a simple HPLC-PDA Method to Determine Drug Entrapment and Evaluation of its Photostability.

Liquid chromatographic method was developed and validated for quantitative determination of quinine in polymeric nanoparticles. The method was performed using a Waters RP-18 column using a mobile phase consisting of acetonitrile:water:triethylamine (60:40:0.01 v/v/v, and pH aqueous phase adjusted to 3.0 with phosphoric acid). The flow rate was 1.0 mL min-1 and the detection was achieved with a UV-PDA set at 232 nm. The response was linear over a range of 12.0 to 24.0 μg.mL-1 (r = 0.9995). The relative standard deviation values for intra-day and inter-day precision studies were less than 2% and the accuracy was 98.8% to Nc1 and 97.3% to Nc2. The samples free of quinine and quinine-loaded polymeric nanoparticles were subjected to photodegradation conditions. A considerable reduction of degradation of quinine occurred in polymeric nanoparticles. Through these results, it was clear that the nanoencapsulation of quinine protects the drug from degradation by exposure to UV-A light. The analytical method was validated according to International Conference on Harmonization Guidelines and Center for Drug Evaluation and Research.

The use of Brazilian vegetable oils in nanoemulsions: an update on preparation and biological applications

ABSTRACT Vegetable oils present important pharmacological properties, which gained ground in the pharmaceutical field. Its encapsulation in nanoemulsions is considered a promising strategy to facilitate the applicability of these natural compounds and to potentiate the actions. These formulations offer several advantages for topical and systemic delivery of cosmetic and pharmaceutical agents including controlled droplet size, protection of the vegetable oil to photo, thermal and volatilization instability and ability to dissolve and stabilize lipophilic drugs. For these reasons, the aim of this review is to report on some characteristics, preparation methods, applications and especially analyze recent research available in the literature concerning the use of vegetable oils with therapeutic characteristics as lipid core in nanoemulsions, specially from Brazilian flora, such as babassu (Orbignya oleifera), aroeira (Schinus molle L.), andiroba (Carapa guaianiensis), casca-de-anta (Drimys brasiliensis Miers), sucupira (Pterodon emarginatus Vogel) and carqueja doce (Stenachaenium megapotamicum) oils.

Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs.

The aim of this work was to investigate if the indomethacin ethyl ester (IndOEt) released from lipid-core nanocapsules (NC) is converted into indomethacin (IndOH) in the intestine lumen, intestine wall or after the particles reach the blood stream. NC-IndOEt had monomodal size distribution (242 nm; PDI 0.2) and zeta potential of -11 mV. The everted rat gut sac model showed IndOEt passage of 0.16 micromol m(-2) through the serosal fluid (30 min). From 15 to 120 min, the IndOEt concentrations in the tissue increased from 6.13 to 27.47 micromol m(-2). No IndOH was formed ex vivo. A fluorescent-NC formulation was used to determine the copolymer bioadhesion (0.012 micromol m(-2)). After NC-IndOEt oral administration to rats, IndOEt and IndOH were detected in the gastrointestinal tract (contents and tissues). In the tissues, the IndOEt concentrations decreased from 459 to 5 microg g(-1) after scrapping, demonstrating the NC mucoadhesion. In plasma (peripheric and portal vein), in spleen and liver, exclusively IndOH was detected. In conclusion, after oral dosing of NC-IndOEt, IndOEt is converted into IndOH in the intestinal lumen and wall before reaching the blood stream. The complexity of a living system was not predicted by the ex vivo gut sac model.

Enteric controlled-release pantoprazole-loaded microparticles prepared by using Eudragit S100 and poly(epsilon-caprolactone) blend.

Microparticles of poly(epsilon-caprolactone) and of its blend with Eudragit S100 were prepared by emulsion/solvent evaporation technique to provide controlled release and gastro-resistance for an acid labile drug. This drug was sodium pantoprazole, a proton pump inhibitor. Both formulations were successfully prepared, but only the microparticles prepared with the blend were capable of stabilizing the drug in the acid medium. Furthermore, this formulation showed in vivo protection of stomachs against ulceration caused by ethanol in rats. These microparticles were tabletted, and the tablets demonstrated slower drug release and higher acid protection than the microparticles before tabletting.

Efeito da utilização de ácidos graxospoliinsaturados ômega-3 microparticulados na cicatrização de enteroanastomose experimental em ratos: resultados preliminares / Microparticulate poliunsatured fat acids (n-3) in the ileal enteroanastomosis healing in rats: preliminary results

Atualmente muito se tem discutido sobre os efeitos benéficos da suplementação de ácidos graxos poliinsaturados (AGP), prevenindo ou auxiliando a terapia de várias doenças. O presente estudo visou avaliar a influência da suplementação com AGPs ômega-3 (n-3) veiculados em micro¬partículas na qualidade de cicatrização intestinal de enteroanastomose ileal em ratos. Para o estudo foram utilizados 30 ratos Wistar fêmeas submetidos à celiotomia mediana e enteroanastomose ileal. Os animais foram distribuídos em dois grupos de tratamento: ao grupo 1 (G1) foram administradas micropartículas de n-3, via oral, de acordo com os diferentes períodos de tratamento e ao grupo 2 (G2) administrou-se cetoprofeno como antiinflamatório padrão, pela mesma via, durante 3 dias. Cada grupo foi dividido em 3 subgrupos de acordo com o período de eutanásia, sendo realizada aos 3, 6 ou 8 dias de pós-operatório. Após os tratamentos, os animais foram submetidos à eutaná¬sia, tendo as cavidades abdominais comparadas macroscopicamente quanto a alterações como: presença de secreção, grau de aderência, deiscência da sutura e formação de abscessos. A avaliação foi realizada atribuindo escores de pontuação às diferentes variáveis. O segmento intestinal do sítio de anastomose foi coletado para análise histológica (a ser publicado posteriormente). Com os dados até então obtidos pode-se concluir que a utilização de n-3 veiculado por micropartículas é vantajosa para o processo de cicatrização intestinal pós-operatória quando comparada com a administração de cetoprofeno. mediana e enteroanastomose ileal(AU)

Beneficial effect of long-chain fatty acids in the prevention or therapy of some illnesses has been reported. The aim of this study was to investigate the influence of supplementation with n-3 fatty acids-loaded microparticles in the healing of intestinal anastomosis in rats. Thirty female Wistar rats were submitted to ileal anastomosis. The animals were divided in two groups of treatment. The group 1 (G1) received n-3 fatty acids microparticles by oral route according to different periods of treatment and the group 2 (G2) (control group) received ketoprofen for three days. The groups were divided in 3 sub-groups according to the period of euthanasia, carried out at 3, 6 or 8 postoperative days. After euthanasia, alterations in the abdominal cavity were compared macroscopically (regarding secretion, degree of adhesion, dehiscence of the suture and abcess formation). The intestinal segment of the anastomosis was collected and processed for histological evaluation (this second stage will be published later). The results showed that the use of n-3-loaded microparticles is beneficial for the process of postoperative intestinal healing when compared with the ketoprofen treatment(AU)

Efeito da utilização de ácidos graxospoliinsaturados ômega-3 microparticulados na cicatrização de enteroanastomose experimental em ratos: resultados preliminares / Microparticulate poliunsatured fat acids (n-3) in the ileal enteroanastomosis healing in rats: preliminary results

Atualmente muito se tem discutido sobre os efeitos benéficos da suplementação de ácidos graxos poliinsaturados (AGP), prevenindo ou auxiliando a terapia de várias doenças. O presente estudo visou avaliar a influência da suplementação com AGPs ômega-3 (n-3) veiculados em micro¬partículas na qualidade de cicatrização intestinal de enteroanastomose ileal em ratos. Para o estudo foram utilizados 30 ratos Wistar fêmeas submetidos à celiotomia mediana e enteroanastomose ileal. Os animais foram distribuídos em dois grupos de tratamento: ao grupo 1 (G1) foram administradas micropartículas de n-3, via oral, de acordo com os diferentes períodos de tratamento e ao grupo 2 (G2) administrou-se cetoprofeno como antiinflamatório padrão, pela mesma via, durante 3 dias. Cada grupo foi dividido em 3 subgrupos de acordo com o período de eutanásia, sendo realizada aos 3, 6 ou 8 dias de pós-operatório. Após os tratamentos, os animais foram submetidos à eutaná¬sia, tendo as cavidades abdominais comparadas macroscopicamente quanto a alterações como: presença de secreção, grau de aderência, deiscência da sutura e formação de abscessos. A avaliação foi realizada atribuindo escores de pontuação às diferentes variáveis. O segmento intestinal do sítio de anastomose foi coletado para análise histológica (a ser publicado posteriormente). Com os dados até então obtidos pode-se concluir que a utilização de n-3 veiculado por micropartículas é vantajosa para o processo de cicatrização intestinal pós-operatória quando comparada com a administração de cetoprofeno. mediana e enteroanastomose ileal

Beneficial effect of long-chain fatty acids in the prevention or therapy of some illnesses has been reported. The aim of this study was to investigate the influence of supplementation with n-3 fatty acids-loaded microparticles in the healing of intestinal anastomosis in rats. Thirty female Wistar rats were submitted to ileal anastomosis. The animals were divided in two groups of treatment. The group 1 (G1) received n-3 fatty acids microparticles by oral route according to different periods of treatment and the group 2 (G2) (control group) received ketoprofen for three days. The groups were divided in 3 sub-groups according to the period of euthanasia, carried out at 3, 6 or 8 postoperative days. After euthanasia, alterations in the abdominal cavity were compared macroscopically (regarding secretion, degree of adhesion, dehiscence of the suture and abcess formation). The intestinal segment of the anastomosis was collected and processed for histological evaluation (this second stage will be published later). The results showed that the use of n-3-loaded microparticles is beneficial for the process of postoperative intestinal healing when compared with the ketoprofen treatment

Utilização de células-tronco autólogas de medula óssea na regeneração do nervo tibial de coelhos mediante técnica de tubulização com prótese de silicone / Applyng of autologous stem cells from bone marrow in the regeneration of tibial nerve of rabbits using the tubulization technique with silicone tube

Neste estudo é apresentado um modelo experimental de defeito agudo em nervo periférico para avaliação da regeneração nervosa mediante técnica de tubulização associada à inoculação de células-tronco autólogas de medula óssea. Foram utilizados 12 coelhos Nova Zelândia albinos, submetidos à secção bilateral e ao afastamento de 5mm do nervo tibial e posterior reparo mediante utilização de câmara de silicone. Internamente à prótese de tubulização do nervo tibial esquerdo em todos os animais, foram inoculadas células-tronco autólogas de medula óssea, coletadas a partir do úmero. Como grupo controle (nervo tibial direito), mediante aplicação da mesma técnica de reparo, solução de NaCl 0,9 por cento foi administrada internamente à prótese. Após 30 dias de observação, os animais foram eutanasiados e foi realizada a avaliação histológica dos segmentos nervosos por meio das colorações de hematoxilina-eosina, luxol fast blue e azul de toluidina. Com os resultados, foi possível concluir que o transplante de células-tronco autólogas associado à técnica de tubulização apresenta vantagens no processo de regeneração nervosa periférica.

This study presents an experimental model of an acute deffect in a peripheral nerve to evaluate neural regeneration using a tubulization technique associated with the inoculation of autologous stem cells from bone marrow. A total of 12 New Zealand white rabbits underwent a bilateral dissection of the tibial nerve followed by repair with silicone tubulization. On the left tibial nerve of all animals, the tube was filled with autologous bone marrow-derived stem cells collected from the humerus. For control, using the same repair technique, the tubes were filled with a NaCl solution in the right tibial nerve. After 30 days of observation, the animals were euthanized and a histological evaluation of the collected nerve segments was performed by staining with hematoxylin-eosin, luxol fast blue, and toluidine blue. From the results it is possible to conclude that the transplanted autologous stem cells associated with the tubulization technique present an advantage in the peripheral nerve regeneration process.