Schistogram changes after administration of antischistosomal drugs in mice at the early phase of Schistosoma mansoni infection

Mice infected with Schistosoma mansoni were treated with oxamniquine, praziquantel, artesunate at the pre-patent phase, aiming at observing schistogram alterations. Half of the animals were perfused five days post-treatment for counting and classification of immature worms, based on pre-established morphological criteria (schistogram); the remaining animals were evaluated 42 or 100 days after infection and perfusion of the portal-system was performed for collection and counting of adult worms and oogram. It was observed that oxamniquine and artesunate treatment administered at the pre-postural phase causes significant reduction in the number of immature and adult worms. However, there was little reduction with praziquantel when used at the dose of 400 mg/kg for treatments administered 14, 15, 21 or 23 days post-infection. Artesunate was responsible for significant alterations in development of young worms, as well as for a higher number of worms presenting intestinal damages. Immature adult worms were detected in mice treated with artesunate or oxamniquine at the pre-patent phase of infection and recovered by perfusion 100 days after infection. Schistogram proved to be a very useful tool for experimental evaluation of the activity of antischistosomal drugs and a good model to identify the most sensitive stages to drugs.

Schistosoma mansoni: avaliação da fibrose hepática em camundongos submetidos quimioterapia e reinfectados / Schistosoma mansoni: assessment of hepatic fibrosis in mice undergoing chemotherapy and reinfected

A esquistossomose mansônica é uma doença parasitária tropical. Causadas por helmintos do gênero Schistosoma. Com a intenção de conter a doença, diversos institutos e organizações vêm desenvolvendo medidas de controle para tratar indivíduos infectados e evitar a ocorrência de novas infecções. Estratégias de administração de medicamentos em massa são eficazes na cura da doença, entretanto o tratamento com drogas anti-helmínticas não previnem a possibilidade da ocorrência de reinfecções. Diante desta questão, neste trabalho propusemo-nos a analisar a cinética da fibrose hepática em camundongos esquistossomóticos tratados e submetidos à reinfecção. Para alcançar este objetivo, 70 camundongos Swiss foram infectados com 50 cercárias de S.mansoni, posteriormente tratados com Oxamniquine ou Praziquantel e reinfectados quatro meses após tratamento. Os fígados destes animais foram submetidos a técnicas de imunohistoquímica e imunofluorescência e microscopia eletrônica de transmissão para avaliação da expressão e participação de componentes envolvidos no processo fibrogênico. Para verificar os índices de colágeno entre os grupos utilizou-se a análise morfométrica. A análise histológica revelou que camundongos esquistossomóticos submetidos à quimioterapia específica desenvolveram altos índices de fibrose durante a reinfecção. A imunomarcação para alfa actina de músculo liso (α-SMA) revelou que grande parte do parênquima hepático dos animais tratados e reinfectados exibiam células com perfil miofibloblástico. A imunofluorescência demonstrou que o padrão de marcação para laminina estava alterado em animais com esquistossomose. A análise morfométrica revelou que reinfecção destes animais ocasionou uma intensa deposição de fibras colágenas no parênquima hepático. Os dados obtidos demonstraram que a reinfecção em animais previamente tratados, foi capaz de induzir uma resposta fibrótica semelhante a encontrada nos animais com infecção primária.

Antibody reactivity against potato apyrase, a protein that shares epitopes with Schistosoma mansoni ATP diphosphohydrolase isoforms, in acute and chronically infected mice, after chemotherapy and reinfection

Schistosoma mansoni ATP diphosphohydrolase isoforms and potato apyrase share conserved epitopes. By enzyme-linked immunosorbent assays, elevated levels of IgM, IgG2a and IgG1 antibody reactivity against potato apyrase were observed in S. mansoni-infected BALB/c mice during the acute phase of infection, while only IgM and IgG1 antibody reactivity levels maintained elevated during the chronic phase of infection. Antibody reactivity against potato apyrase was monitored over an 11-month period in chronically-infected mice treated with oxamniquine. Eleven months later, the level of seropositive IgM decreased significantly (~30 percent) compared to the level found in untreated, infected mice. The level of seropositive IgG1 decreased significantly four months after treatment (MAT) (61 percent) and remained at this level even after 11 months. The IgG2a reactivity against potato apyrase, although unchanged during chronic phase to 11 MAT, appeared elevated again in re-infected mice suggesting a response similar to that found during the acute phase. BALB/c mouse polyclonal anti-potato apyrase IgG reacted with soluble egg antigens probably due to the recognition of parasite ATP diphosphohydrolase. This study, for the first time, showed that the IgG2a antibody from S. mansoni-infected BALB mice cross-reacts with potato apyrase and the level of IgG2a in infected mice differentiates disease phases. The results also suggest that different conserved-epitopes contribute to the immune response in schistosomiasis.

Specific schistosomiasis treatment as a strategy for disease control

The great hope for schistosomiasis treatment began with the development of oxamniquine and praziquantel. These drugs can be administered orally in a single dose and have a high curative power with minor side effects. In this study, we carried out a field experiment involving a population of 3,782 people. The population was examined at four localities in Minas Gerais within the valleys of the Doce and Jequitinhonha Rivers. In this cohort, there were 1,790 patients infected with Schistosoma mansoni (47.3 percent) and we showed that only 1,403 (78.4 percent) could be treated with oxamniquine in a single dose of 12.5-20 mg/kg orally. The other 387 (21.6 percent) were not treated during the first stage because of contraindications (pregnancy or impeditive diseases), absences or refusals. It was observed that, on average, 8.8-17 percent of the infected patients continued to excrete S. mansoni eggs at the end of the 2nd month after treatment and 30-32 percent of the cohort was infected by the end of the 24th month. In one of the areas that we followed-up for a total of 30 years, the prevalence of the infection with S. mansoni fell from 60.8-19.3 percent and the hepatosplenic form of the disease dropped from 5.8-1.3 percent. We conclude that specific treatment of schistosomiasis reduces the prevalence of infection in the short-term and the morbidity due to schistosomiasis in medium to long-term time frames, but does not help to control disease transmission.

Schistosoma mansoni: a rare cause of tubal infection

S. haematobium is an important cause of urinary schistosomiasis, and symptomatic female genital infection is a common gynecological finding in areas where S. haematobium is prevalent. On the other hand, genital manifestations of intestinal schistosomas as S. mansoni are not frequent or are misdiagnosed. A case of a 40-year-old woman with abnormal uterine bleeding and asymptomatic tubal infection by S. mansoni identified in histological examination is presented.

Schistosomiasis mansoni of the bladder simulating bladder cancer: a case report / Esquistossomose mansônica simulando câncer de bexiga: relato de caso

The relationship between bladder tumors and Schistosoma haematobium is well known, but only sporadic cases of bladder infection due to Schistosoma mansoni have been reported. In this case, a 48-year-old woman with macroscopic hematuria, dysuria and a palpable abdominal mass was investigated. Ultrasound showed a large exophytic mass in the bladder. Transurethral resection of the bladder revealed viable eggs of Schistosoma mansoni. The patient was treated clinically with oxamniquine and surgery was performed to resect the large mass. This case shows that schistosomiasis Mansoni in the bladder can simulate bladder cancer.

É bem conhecida a relação entre tumor vesical e Schistosoma haematobium, porém somente casos esporádicos de infecção vesical por Schistosoma mansoni foram relatados. Neste caso, uma mulher de 48 anos com hematúria macroscópica, disúria e massa abdominal palpável foi investigada, ultra-sonografia mostrou uma grande massa exofítica na bexiga. A ressecção transuretral de bexiga evidenciou ovos viáveis de Schistosoma mansoni. A paciente foi tratada clinicamente com oxaminiquine e uma cirurgia foi realizada para ressecar a grande massa. Este caso mostra que a esquistossomose mansônica vesical pode simular um câncer vesical.

Síntese e atividade biológica do derivado 6-formil-oxamniquina / Synthesis and biological activity of 6-formyl-oxamniquine derivative

A esquistossomose, uma importante doença no Brasil, é causada por trematódeo pertencente ao gênero Schistosoma, atingindo milhões de pessoas, numa das maiores regiões endêmicas dessa doença em todo globo. O principal objetivo desse trabalho foi sintetizar o derivado 6-formil-oxamniquina e avaliar sua atividade biológica. O derivado 6-formil- oxamniquina foi obtido por oxidação da oxamniquina com dióxido de manganês empregando diclorometano como solvente, à temperatura ambiente, por 24 horas. Sua obtenção foi confirmada por espectrometria na região de infravermelho e espectroscopia de RMN 13C e ÕH, apresentando atividade similar quando comparada à oxamniquina comercial (Mansil®).

Schistosomiasis, an important disease in Brazil, is caused by a trematode of the genus Schistosoma, reaching millions of person in one of the most endemic region of this disease in the whole globe. The main goal of this work was to syntetize the 6-formyl-oxamniquine derivative and evaluate its biological activity. The 6-formyl-oxamniquine derivative was obtained by the oxidation of oxamniquine with MnO2, applying CH2Cl2 as solvent at room temperature for 24 hours. The obtaintion of 6-formyl-oxamniquine derivative compound was confirmed by IR spectroscopy and 13C NMR and ÕH NMR, presenting similar activity when compared to the commercial oxamniquine (Mansil®).

Association of oxamniquine praziquantel and clonazepam in experimental Schistosomiasis mansoni

The antischistosomal activity of clonazepam, when administered alone or in association with oxamniquine and praziquantel, was experimentally evaluated in mice infected with Schistosoma mansoni. The animals were treated 45 days post-infection with a single dose, by oral route, according to three treatment schedules: clonazepam 25 mg/kg and sacrificed 15 min, 1h or 4 h after treatment; clonazepam 1.0, 2.5 or 10.0 mg/kg and sacrificed 15 days post-treatment or with the dose of 10 mg/kg in association with oxamniquine 50 mg/kg or praziquantel 200 mg/kg, single dose, orally, every schedule with a control group. The efficacy of the drugs in vivo was assessed by means of worm counts and their distribution in mesentery and liver, mortality and oogram changes. In the chemotherapeutic schedules used, clonazepam did not present antischistosomal activity and the result of the association of this drug with oxamniquine or praziquantel was not significantly different from the one obtained when these two last drugs were administered alone. In the in vitro experiments, the worms exposed to 0.6 mg/mL clonazepam remained motionless throughout the 8-day-period of observation, without egg-laying, whereas the worms of the control group showed normal movements, egg-laying and hatching of miracidia on the last day of observation. The results obtained in the present study confirm the action of clonazepam on S. mansoni adult worm, in vitro, causing total paralysis of males and females. However, no additive or synergistic effects were observed when clonazepam were used in association with oxamniquine or praziquantel.

Oxamniquine, praziquantel and lovastatin association in the experimental Schistosomiasis mansoni

The activity of lovastatin associated with oxamniquine or praziquantel against schistosomiasis mansoni was evaluated in mice infected with Schistosoma mansoni. Forty days after infection, mice were treated with lovastatin, 400 mg/kg for five consecutive days by oral route, and on the last day of this sequence with 50 mg/kg oxamniquine or with 200 mg/kg praziquantel, both by oral route, single dose. Fifteen days later, the animals were perfused in parallel with an untreated control group. Studies were carried out in vitro, using lovastatin in culture medium containing S. mansoni worms proceeding from experimentally infected mice. In the in vivo trials, the association of lovastatin with oxamniquine or praziquantel did not show any additive action, but there were oogram changes when lovastatin was associated with oxamniquine. In vitro lovastatin was able to interrupt the maturation of S. mansoni eggs, which remained at the 1st or 2nd stages, depending on the dose used. The total number of morphologically dead eggs found in culture of worms exposed to 2 µg/ml or 4 µg/ml concentrations of lovastatin was significantly higher than the number of viable eggs. Using the probe Hoescht 33258 it was observed that 70 percent of the eggs considered morphologically viable in the treated groups (against 16 percent in the control group) were labeled, indicating that the majority of the viable eggs had membrane permeability increased due to lovastatin action.

Testicular schistosomiasis caused by Schistosoma mansoni: a case report from Brazil

Testicular schistosomiasis by Schistosoma mansoni is exceedingly rare, with only 11 cases reported in PubMed. We report a new case from Brazil. A 31-year-old man from the northeast region of the country presented with a 2 cm nodule in the right testis. Ultrasonography showed a well-delimited hypoechoic tumor, suggestive of a granulomatous lesion. Magnetic resonance imaging revealed an irregular tunica albuginea signal. A biopsy showed interstitial tissue with schistosome ova and granuloma formation. The nodule was excised, and the patient was treated with oxamniquine. He has remained symptom free for 10 years. A testicular nodule should raise suspicion of numerous pathologies, including schistosomiasis. Treatment should include therapy with oxamniquine or praziquantel, and nodule excision should be done whenever possible.

Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-gamma response to Schistosoma mansoni antigens

Patients with acute schistosomiasis were studied before and after oxamniquine treatment. They had been exposed to cercariae 5 to 9 weeks before, and presented compatible clinical manifestations, eosinophilia, and high levels of total IgE. Interferon-gamma (IFN-gamma) and interleukin-4 were measured by ELISA in whole blood samples under soluble egg antigen or soluble adult worm preparation stimulation. After treatment, the reduction of leukocytosis and eosinophilia were not significant, but total IgE levels decreased significantly, in contrast to IFN-gamma levels that were significantly increased. The oxamniquine treatment of acute schistosomiasis patients is followed by an improvement of a Th1 response in vitro. If this response has a protective aspect is unknown, and some investigations need to be realized.

Pólipo retal inflamatório esquistossomótico de margem anal / Rectal inflamatory schistosomotic polyp in the anal margin

Paciente do sexo feminino, 11 anos, apresentando sangramento retal por três dias, com piora nas últimas 24 horas. Admitida com sinais de instabilidade hemodinâmica e massa polipóide vegetante aderida à mucosa retal. Ressecção e hemostasia foram realizadas em ambiente cirúrgico. A etiologia da lesão foi confirmada microscopicamente pela presença de diversos ovos e vermes adultos de Schistosoma mansoni. Realizou-se tratamento com oxaminiquine 20mg/kg em duas doses. Após três semanas a paciente recebeu alta do hospital assintomática e em boas condições.

Clinical-epidemiological profile of children with schistosomal myeloradiculopathy attended at the Instituto Materno-Infantil de Pernambuco

The most critical phase of exposure to schistosomal infection is the infancy, because of the more frequent contact with contaminated water and the immaturity of the immune system. One of the most severe presentations of this parasitosis is the involvement of the spinal cord, which prognosis is largely dependent on early diagnosis and treatment. Reports on this clinical form of schistosomiasis in children are rare in the literature. We present here the clinical-epidemiological profile of schistosomal myeloradiculopathy (SMR) from ten children who were admitted at the Instituto Materno-Infantil de Pernambuco over a five-year period. They were evaluated according to an investigation protocol. Most of these patients presented an acute neurological picture which included as the main clinical manifestations: sphincteral disorders, low back and lower limbs pain, paresthesia, lower limbs muscle weakness and absence of deep tendon reflex, and impairment of the gait. The diagnosis was presumptive in the majority of the cases. This study emphasizes the importance of considering the diagnosis of SMR in pediatric patients coming from endemic areas who present a low cord syndrome, in order to start the appropriate therapy and avoid future complications.

Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis

Hepatosplenic schistosomiasis was the first human disease in which the possibility of extensive long standing hepatic fibrosis being degraded and removed has been demonstrated. When such changes occurred, the main signs of portal hypertension (splenomegaly, esophageal varices) progressively disappeared, implying that a profound vascular remodeling was concomitantly occurring. Hepatic vascular alterations associated with advanced schistosomiasis have already been investigated. Obstruction of the intrahepatic portal vein branches, plus marked angiogenesis and compensatory hyperplasia and hypertrophy of the arterial tree are the main changes present. However, there are no data revealing how these vascular changes behave during the process of fibrosis regression. Here the mouse model of pipestem fibrosis was used in an investigation about these vascular alterations during the course of the infection, and also after treatment and cure of the disease. Animals representing the two polar hepatic forms of the infection were included: (1) "isolated granulomas" characterized by isolated periovular granulomas sparsely distributed throughout the hepatica parenchyma; and (2) 'pipestem fibrosis' with periovular granulomas and fibrosis being concentrated within portal spaces, before and after treatment, were studied by means of histological and vascular injection-corrosion techniques. Instances of widespread portal vein obstruction of several types were commonly found in the livers of the untreated animals. These obstructive lesions were soon repaired, and completely disappeared four months following specific treatment of schistosomiasis. Treatment was accomplished by the simultaneous administration of praziquantel and oxamniquine. The most impressive results were revealed by the technique of injection of colored masses into the portal system, followed by corrosion in strong acid. The vascular lesions of non-treated pipestem fibrosis were represented...

The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase

Available evidence suggests that the antischistosomal drug oxamniquine is converted to a reactive ester by a schistosome enzyme that is missing in drug-resistant parasites. This study presents data supporting the idea that the active ester is a sulfate and the activating enzyme is a sulfotransferase. Evidence comes from the fact that the parasite extract loses its activating capability upon dialysis, implying the requirement of some dialyzable cofactor. The addition of the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) restored activity of the dialyzate, a strong indication that a sulfotransferase is probably involved. Classical sulfotransferase substrates like beta-estradiol and quercetin competitively inhibited the activation of oxamniquine. Furthermore, these substrates could be sulfonated in vitro using an extract of sensitive (but not resistant) schistosomes. Gel filtration analysis showed that the activating factor eluted in a fraction corresponding to a molecular mass of about 32 kDa, which is the average size of typical sulfotransferase subunits. Ion exchange and affinity chromatography confirmed the sulfotransferase nature of the enzyme. Putative sulfotransferases present in schistosome databases are being examined for their possible role as oxamniquine activators.

Esquistossomose mansônica simulando neoplasia da bexiga / Schistosomiasis mansoni simulating bladder neoplasia

Paciente de 36 anos de idade, proveniente de zona endêmica foi admitido com episódios de hematúria macroscópica total e disúria terminal. A citoscopia mostrou um tumor exofítico na parede anterior da bexiga, sugestivo de câncer. A biópsia revelou esquistossomose mansônica. Ressecção transuretral confirmou o diagnóstico. O paciente foi clinicamente tratado com oxamniquine, obtendo cura. O caso apresentado nesse trabalho enfatiza que nem todos os tumores de bexiga com hematúria microscópica são cânceres de bexiga.

Avaliação do efeito do praziquantel, da oxamniquina e da associação destas drogas sobre o verme adulto de Schistosoma mansoni / Evaluation of the effect of praziquantel, the oxamniquina and the association of these drugs on the adult worm of Schistosoma mansoni

O presente estudo teve como objetivo avaliar o potencial terapêutico da associação de oxamniquina (OXA) e praziquantel (PZQ), no tratamento da esquistossomose mansoni, por meio de experimentos "in vivo" e "in vitro". A ação das drogas em associação foi comparada ao efeito de cada droga utilizada isoladamente, em camundongos experimentalmente infectados. As associações de OXA e PZQ utilizadas (50 mg/Kg de OXA + 100 mg/Kg de PZQ e 100 mg/Kg de OXA + 200 mg/Kg de PZQ) mostraram-se mais efetivas na redução do número de vermes quando comparados ao tratamento com 400 mg/Kg de PZQ, empregado separadamente. A associação na maior dosagem foi o único esquema terapêutico capaz de eliminar todos os parasitos dos animais. Em adição, a maior susceptibilidade dos parasitos machos à OXA e das fêmeas ao PZQ foi confirmada, podendo explicar pelo menos em parte, a maior eficácia da combinação de ambas as drogas. A possível sinergia das drogas também foi estudada, avaliando-se o efeito dessas isoladamente ou em associação, sobre o sistema excretor e sobre a membrana tegumentar de vermes adultos de Schistosoma mansoni, através do uso de marcadores fluorescentes "in vitro". Para tanto, os parasitos foram expostos diretamente às drogas ou recuperados após duas horas do tratamento de animais infectados. Pela primeira vez, foi demonstrada a atuação do PZQ no sistema excretor de vermes adultos de S. mansoni. O PZQ atuou inibindo a atividade excretora dos parasitos machos, porém esta atividade foi recuperada, logo após a retirada da droga. Os parasitos fêmeas não acasalados apresentaram nítida atividade excretora, independentemente da exposição às drogas, ao passo que as fêmeas acasaladas somente tiveram seu sistema excretor ativo quando expostos a agentes agressores externos, não apresentando nenhum sinal de atividade, em condições normais (sem exposição às drogas). A associação OXA/PZQ mostrou causar danos mais intensos na membrana tegumentar dos parasitos em relação àqueles...

Comparative clinical and ultrasound study of egg-negative and egg-positive individuals from Schistosoma mansoni low morbidity endemic areas, and hospitalized patients with hepatosplenic disease

Duzentos e vinte e três indivíduos de área endêmica de baixa morbidade para esquistossomose e nove pacientes hospitalizados com a forma hepatoesplênica foram submetidos ao exame de fezes e clínico e à ultra-sonografia do abdômen. De acordo com os resultado dos exames de fezes e do ultra-som eles foram agrupados do seguinte modo: G1 - 63 indivíduos sem ovos de Schistosoma mansoni nas fezes; G2 - 141 indivíduos apresentando ovos de Schistosoma mansoni nas fezes, sem ecogenicidade periportal. G3 — 19 indivíduos com ovos de Schistosoma mansoni nas fezes e ecogenicidade periportal entre 3-6mm.; G4 — 9 pacientes hepatesplênicos com ecogenicidade periportal > 6mm. Pelo exame físico do abdômen, a hepatomegalia na linha hemiclavicular direita foi constatada em G1, G2 E G3, respectivamente, em 11,1, 12,1 e 26,3%. Nos grupos G1, G2 e G3, houve espessamento periportal somente em esquistossomáticos (8,5%). Alterações patológicas leves em pacientes, as quais não puderam ser detectadas pelo exame clínico, foram evidenciadas no fígado pelo ultra-som e podem ser devidas à fibrose. O grau de fibrose periportal leve foi diminuído em 57,9% dos pacientes 12 meses após tratamento da esquistossomose com oxamniquine. Na ultra-sonografia, a média da medida do lobo esquerdo do fígado dos indivíduos de G3 foi maior que a de G1 e, a de G4 maior que a de G1 e G2. O tamanho médio do baço de G4 foi significativamente maior que o dos outros grupos e o de G3 foi maior que o de G1 e G2.

Avaliação do efeito do praziquantel, da oxamniquina e da associação destas drogas sobre o verme adulto de Schistosoma mansoni / Evaluation of the effect of praziquantel, the oxamniquina and the association of these drugs on the adult worm of Schistosoma mansoni

O presente estudo teve como objetivo avaliar o potencial terapêutico da associação de oxamniquina (OXA) e praziquantel (PZQ), no tratamento da esquistossomose mansoni, por meio de experimentos "in vivo" e "in vitro". A ação das drogas em associação foi comparada ao efeito de cada droga utilizada isoladamente, em camundongos experimentalmente infectados. As associações de OXA e PZQ utilizadas (50 mg/Kg de OXA + 100 mg/Kg de PZQ e 100 mg/Kg de OXA + 200 mg/Kg de PZQ) mostraram-se mais efetivas na redução do número de vermes quando comparados ao tratamento com 400 mg/Kg de PZQ, empregado separadamente. A associação na maior dosagem foi o único esquema terapêutico capaz de eliminar todos os parasitos dos animais. Em adição, a maior susceptibilidade dos parasitos machos à OXA e das fêmeas ao PZQ foi confirmada, podendo explicar pelo menos em parte, a maior eficácia da combinação de ambas as drogas. A possível sinergia das drogas também foi estudada, avaliando-se o efeito dessas isoladamente ou em associação, sobre o sistema excretor e sobre a membrana tegumentar de vermes adultos de Schistosoma mansoni, através do uso de marcadores fluorescentes "in vitro". Para tanto, os parasitos foram expostos diretamente às drogas ou recuperados após duas horas do tratamento de animais infectados. Pela primeira vez, foi demonstrada a atuação do PZQ no sistema excretor de vermes adultos de S. mansoni. O PZQ atuou inibindo a atividade excretora dos parasitos machos, porém esta apresentaram nítida atividade excretora,independentemente da exposição às drogas, ao passo que as fêmeas acasaladas somente tiveram seu sistema excretor ativo quando expostos a agentes agressores externos, não apresentando nenhum sinal de atividade, em condições normais (sem exposição às drogas). A associação OXA/PZQ mostrou causar danos mais intensos na membrana tegumentar dos parasitos em relação àqueles provocados pelo uso das drogas usadas separadamente. Os resultados obtidos, com este trabalho, aponta...

Three months chemoprophylaxis of shistosomiasis using liposome encapsulated oxamniquine

Oxamniquine liposomes of the molar ratio 7:6, neutral and negatively charged, were prepared by the vortex dispersion method. Entrapped oxamniquine was estimated by HPLC analysis. Percentage drug encapsulated was found to range from 12.4% [neutral liposomes] to 20% [negative liposomes]. Drug-free and oxamniquine liposomes were characterized by particle-size analysis and Differential-scanning-calorimetry. Liver disposition of oxamniquine liposomes in mice, three-months post [s.c.] injection was investigated. Results reveal that oxamniquine liposomes are better liver-targeted than the free drug. Chemoprophylaxis of oxamniquine liposomes against S. mansoni in mice, was assessed for three months where drug liposomes displayed highly significant protection of 44%, unlike the free drug preparation; 1.3%. Stability study of oxamniquine liposomes was conducted on negative and neutral liposomes at -10, 4°, and 25°. Neutral liposomes displayed better sustained release of the drug over the negative ones. Storage at -10° provides more stable drug- liposomes. Sterilization of negatively charged oxamniquine liposomes was conducted employing four doses of gamma radiation of 10, 15, 20 and 25 KGy. Results revealed that 25 KGy is the optimum sterilizing dose, in addition to inferring high stability to the product