Nanostructured Systems in Advanced Drug Targeting for the Cancer Treatment: Recent Patents.

BACKGROUND: Cancer is one of the leading causes of death in the world and it is necessary to develop new strategies for its treatment because most therapies have limited access to many types of tumors, as well as low therapeutic efficacy and high toxicity. OBJECTIVE: The present research aims to identify recent patents of drug delivery nanostructured systems that may have application in improving cancer treatment. METHODS: Recent patents regarding the drug delivery nanostructured systems for cancer treatment were obtained from the patent databases of the six main patent offices of the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Intellectual Property Office of China and Korean Intellectual Property Office. RESULTS: A total of 1710 patent documents from 1998 to 2017 including "drug delivery nanostructured systems for cancer treatment" were retrieved. The top five countries in patent share were USA, China, South Korea, Canada and Germany. The universities and enterprises of USA had the highest amount of patents followed by institutions from China. CONCLUSION: There is a strong tendency for the development of new nanostructured systems for the release of drugs; particularly, in recent years, the development of nanoparticles has focused on nanodiscs, gold nanoparticles and immunoliposomes.

La inmunización con productos de excreción-secreción de Trichinella spiralis unido al bloqueo de CTLA-4 produce un elevado grado de protección ante un reto con el parásito / Immunization with excretion-secretion products of Trichinella spiralis combined to CTLA-4 blockade produces a high degree of protection against a challenge with the parasite

En la búsqueda de una vacuna experimental efectiva contra Trichinella spiralis se han utilizado diferentes estrategias, pero el grado de protección alcanzado en la casi totalidad de los ensayos es insuficiente para lograr un adecuado control de la enfermedad. En la literatura hay evidencias de que moléculas inhibidoras de la activación de los linfocitos T están implicadas en la regulación de la respuesta inmune contra los helmintos. El bloqueo de estas moléculas puede ser un blanco potencial para el tratamiento de las infecciones causadas por estos parásitos. Por otra parte, se ha informado que la inmunización con productos de excreción-secreción de larvas musculares de T. spiralis proporciona una inmunidad protectora parcial. La infección con el parásito induce una elevada población de linfocitos T reguladores que modulan la respuesta inmune. En este trabajo encontramos que la inmunización con antígenos de excreción-secreción de larvas musculares, más el bloqueo de la molécula inhibidora CTLA-4 en los linfocitos T, causa una significativa reducción de las larvas del parásito en un modelo experimental murino. De esta forma, queda demostrado que la eliminación del efecto supresor inducido por el helminto da por resultado una respuesta Th2 protectora más potente(AU)

Different approaches to vaccination against T. spiralis using murine experimental models have been used, but the levels of protection observed in most experimental trials may not be sufficient to provide a good disease control. There is increasing evidence that inhibitors molecules on T cells are critically involved in the regulation of immune response against helminths infections, thus negative stimulators represent possible drug targets since their blockade leads to an increased immune response. Moreover, it has been reported that immunization with excretory-secretory products of T. spiralis muscular larvae could provide partial protective immunity against parasite infection. T. spiralis induce a population of cells with elevated levels of known markers of T regulatory, manipulation of which influences the immune response and parasite load. In the present work we found that immunization with muscle larvae excretory secretory products of T. spiralis and blockade of CTLA-4 displayed remarkable high reduction of muscle larvae burdens in a murine model, showing that elimination of suppressive regulatory pathways results in a more potent and protective The response which reduces muscle larval establishment(AU)

Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico.

The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P < 0.01) for low seropositivity (r = 0.93) and medium seropositivity (r = 0.84). The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans.

La inmunización con productos de excreción-secreción de Trichinella spiralis unido al bloqueo de CTLA-4 produce un elevado grado de protección ante un reto con el parásito / Immunization with excretion-secretion products of Trichinella spiralis combined to CTLA-4 blockade produces a high degree of protection against a challenge with the parasite

En la búsqueda de una vacuna experimental efectiva contra Trichinella spiralis se han utilizado diferentes estrategias, pero el grado de protección alcanzado en la casi totalidad de los ensayos es insuficiente para lograr un adecuado control de la enfermedad. En la literatura hay evidencias de que moléculas inhibidoras de la activación de los linfocitos T están implicadas en la regulación de la respuesta inmune contra los helmintos. El bloqueo de estas moléculas puede ser un blanco potencial para el tratamiento de las infecciones causadas por estos parásitos. Por otra parte, se ha informado que la inmunización con productos de excreción-secreción de larvas musculares de T. spiralis proporciona una inmunidad protectora parcial. La infección con el parásito induce una elevada población de linfocitos T reguladores que modulan la respuesta inmune. En este trabajo encontramos que la inmunización con antígenos de excreción-secreción de larvas musculares, más el bloqueo de la molécula inhibidora CTLA-4 en los linfocitos T, causa una significativa reducción de las larvas del parásito en un modelo experimental murino. De esta forma, queda demostrado que la eliminación del efecto supresor inducido por el helminto da por resultado una respuesta Th2 protectora más potente(AU)

Different approaches to vaccination against T. spiralis using murine experimental models have been used, but the levels of protection observed in most experimental trials may not be sufficient to provide a good disease control. There is increasing evidence that inhibitors molecules on T cells are critically involved in the regulation of immune response against helminths infections, thus negative stimulators represent possible drug targets since their blockade leads to an increased immune response. Moreover, it has been reported that immunization with excretory-secretory products of T. spiralis muscular larvae could provide partial protective immunity against parasite infection. T. spiralis induce a population of cells with elevated levels of known markers of T regulatory, manipulation of which influences the immune response and parasite load. In the present work we found that immunization with muscle larvae excretory secretory products of T. spiralis and blockade of CTLA-4 displayed remarkable high reduction of muscle larvae burdens in a murine model, showing that elimination of suppressive regulatory pathways results in a more potent and protective The response which reduces muscle larval establishment(AU)

Lethal effects of a Mexican Beauveria bassiana (Balsamo) strain against Meccus pallidipennis (Stal).

The entomopathogenic fungus Beauveria bassiana (Balsamo 1835) Vuillemin is an effective alternative control agent against some agricultural pests and biological vectors of important diseases such as Chagas disease. In this work we studied an isolate of Beauveria bassiana from of the town of San Antonio Rayón, Puebla, Mexico and its entomopathogenic effects on Meccus pallidipennis (Stal 1872). Phylogenetic analysis using molecular comparison of the ITS and EF1α genes, showed that the resulting cladogram places the BUAP 04 strain with a relationship closer to the AFAO 9-6 strain, within the diversity of the B. bassiana sensu lato group. Although there was the possibility that BUAP 04 strain was a direct descendant of strains used in campaigns of biologic control, molecular study allowed us to recognize that it was a different fungus due to numerous inserts. A strain isolated from a T. dimiata was evaluated for pathogenicity against another triatoma (Meccus pallidipennis) species obtaining an LC50 of 4.16 × 10(6) spores/mL, confirming that the BUAP 04 strain is virulent for M. pallidipennis and could be a good prospect for formulations to control M. pallidipennis.

Lethal effects of a Mexican Beauveria bassiana (Balsamo) strain against Meccus pallidipennis (Stal)

The entomopathogenic fungus Beauveria bassiana (Balsamo 1835) Vuillemin is an effective alternative control agent against some agricultural pests and biological vectors of important diseases such as Chagas disease. In this work we studied an isolate of Beauveria bassiana from of the town of San Antonio Rayón, Puebla, Mexico and its entomopathogenic effects on Meccus pallidipennis (Stal 1872). Phylogenetic analysis using molecular comparison of the ITS and EF1α genes, showed that the resulting cladogram places the BUAP 04 strain with a relationship closer to the AFAO 9-6 strain, within the diversity of the B. bassiana sensu lato group. Although there was the possibility that BUAP 04 strain was a direct descendant of strains used in campaigns of biologic control, molecular study allowed us to recognize that it was a different fungus due to numerous inserts. A strain isolated from a T. dimiata was evaluated for pathogenicity against another triatoma (Meccus pallidipennis) species obtaining an LC50 of 4.16 x 10(6) spores/mL, confirming that the BUAP 04 strain is virulent for M. pallidipennis and could be a good prospect for formulations to control M. pallidipennis.

Fascioliasis and intestinal parasitoses affecting schoolchildren in Atlixco, Puebla State, Mexico: epidemiology and treatment with nitazoxanide.

BACKGROUND: The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude) through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries. METHODOLOGY AND FINDINGS: A total of 865 6-14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato-Katz. Fascioliasis prevalences ranged 2.94-13.33% according to localities (mean 5.78%). Intensities were however low (24-384 epg). The association between fascioliasis and the habit of eating raw vegetables was identified, including watercress and radish with pronouncedly higher relative risk than lettuce, corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides infection resulted in risk factors for F. hepatica infection. Nitazoxanide efficacy against fascioliasis was 94.0% and 100% after first and second treatment courses, respectively. The few children, for whom a second treatment course was needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis, B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius vermicularis. A second treatment course was needed for all children affected by ancylostomatids. CONCLUSIONS: Fascioliasis prevalences indicate this area to be mesoendemic, with isolated hyperendemic foci. This is the first time that a human fascioliasis endemic area is described in North America. Nitazoxanide appears as an appropriate alternative to triclabendazole, the present drug of choice for chronic fascioliasis. Its wide spectrum efficacy against intestinal protozooses and helminthiasis, usually coinfecting liver fluke infected subjects in human endemic areas, represents an important added value.

Estudio de los tejidos de moluscos Lymnaea truncatula y Lymnaea cubensis infectados por miracidios de Fasciola hepatica / Study of Lymnaea truncatula and Lymnaea cubensis mollusk tissues infected by Fasciola hepatica miracidia

En el presente trabajo se estudiaron las vías de penetración del miracidio de Fasciola hepática (Linnaeus, 1758) dentro del hepatopáncreas de Lymnaea truncatula (Müller, 1774) y Lymnaea cubensis (Pfeiffer, 1839), en 2 moluscos obtenidos de las zonas endémicas de Fasciolosis de Rusia y de la República Mexicana respectivamente¹. El trayecto de la larva mostró la disolución de la sustancia intercelular y deformación de células epiteliales de los tejidos de los moluscos. A nivel citológico se observaron cambios en el epitelio lineal de cobertura de los ductos de la glándula digestiva y en el tejido conjuntivo del hepatopáncreas. Se observaron diferencias en las vías de penetración y afectación en las dos especies de moluscos estudiados, marcando así las diferencias de las condiciones ecológicas que prevalecen en cada zona geográfica.

The present work investigated the penetration pathways of Fasciola hepática (Linnaeus, 1758) into the hepatopancreas of Lymnaea truncatula (Muller, 1774) and Lymnaea cubensis (Pfeiffer, 1839), two mollusks obtained from Fasciolosis endemic areas in Russia and Mexico, respectively. The larval trajectory showed dissolution of intercellular substance and deformation of epithelial cells of mollusk's tissues. Cytological changes in the ductal epithelium of the digestive gland and in the connective tissue of hepatopancreas were found. Some differences in the penetration and damage pathways in the two species of mollusks studied were observed; thus highlighting the differences in the environmental conditions prevailing in each geographic area.

Trichinella spiralis: monoclonal antibody against the muscular larvae for the detection of circulating and fecal antigens in experimentally infected rats.

In this work we search for antigens of Trichinella spiralis in sera and stool of rats experimentally infected. The kinetic of antibodies to excretory and secretory (ES) antigens of muscle larvae (ML) was also determined. Wistar rats were infected with 15 ML per gram of body weight and blood samples were collected weekly for 10 weeks. Antibodies were studied using an indirect ELISA. For detection of circulating antigens and coproantigens, a sandwich ELISA was developed with the use of polyclonal rabbit antibodies obtained against the total extract of ML and an IgM monoclonal antibody (Mab) against ES antigens of ML. No reactivity was observed between Mab and the total worm antigens of Angiostrongylus cantonensis, Ascaris suum, Echinococcus granulosus, Fasciola hepatica, Strongyloides stercoralis, Taenia solium, Toxocara canis and Trichuris trichiura. The IgM Mab recognized antigens of 45, 49, and 55 kDa in ES antigens and was unable to bind ES antigens deglycosylated with trifluoromethanesulphonic acid (TFMS) indicating that a glycan structure is present in the epitope recognized by this Mab. The sensitivity of sandwich ELISA was 1 ng/mL. Circulating antigens were detected in all infected rats between 3 and 8 weeks post infection and coproantigens were found during the first two days post infection. Antibodies were detected since the third week post infection through the end of experiment. These results suggested that antigen detection by our sandwich ELISA could be a useful complementary laboratory test for antibody detection.

[Biotic and abiotic determinants of seroprevalence of antibodies against Trypanosoma cruzi in Palmar de Bravo, Puebla, Mexico]. / Factores bióticos y abióticos que determinan la seroprevalencia de anticuerpos contra Trypanosoma cruzi en el municipio de Palmar de Bravo, Puebla, México.

OBJECTIVE: To establish the relationship between seroprevalence for antibodies against Trypanosoma cruzi and its relationship with biotic and abiotic factors. MATERIAL AND METHODS: A cross-sectional study was conducted between August 2000 and September 2001. The study population consisted of a simple random sample of 390 volunteers residing in Palmar de Bravo, Puebla, Mexico. Sample and data collection procedures included assaying antibodies against T. cruzi with validated assays, and searching for domestic reservoirs and triatomine bugs. The relationship between biotic and abiotic factors with seropositivity was assessed. Statistical analysis was conducted using Kappa values for diagnostic tests; statistical significance was assessed with 2 x 2 tables, chi-squared test with Yates' correction, Fisher exact test, and odds ratios. RESULTS: The seroprevalence of T. cruzi infection in humans was 4%; in domestic reservoirs (horses, pigs, and dogs) only 10% of canine reservoirs were positive. Vector species recognized were T. borberi and T. pallidipennis, with a Dispersion Area Index and a Colonization Index of 55% and 40%, respectively. The most important risk factors associated with positive serology were altitude (>2,150 and <2,180 meters above sea level), presence of triatomines, age, time of residence, and participation in a social assistance program. CONCLUSIONS: T. cruzi infection was identified in human beings, vectors, and possibly in domestic reservoirs, in communities located over 2,000 meters above sea level.

Factores bióticos y abióticos que determinan la seroprevalencia de anticuerpos contra Trypanosoma Cruzi en el municipio de Palmar de Bravo, Puebla, México / Biotic and abiotic determinants of seroprevalence of antibodies against Trypanosoma cruzi in Palmar de Bravo, Puebla, Mexico

OBJETIVO: Determinar la prevalencia de anticuerpos contra Trypanosoma cruzi y su relación con los factores bióticos y abióticos en Palmar de Bravo, Puebla, México. MATERIAL Y MÉTODOS: Estudio transversal efectuado en agosto de 2000 a septiembre de 2001, con una muestra aleatoria simple de 390 voluntarios residentes en Palmar de Bravo, Puebla, México. Se hizo determinación de anticuerpos contra T cruzi con técnicas serológicas validadas, búsqueda del vector y de reservorios domésticos, así como determinación de asociación entre caso positivo y factores de riesgo bióticos y abióticos. El análisis estadístico consistió en índice Kappa para las pruebas diagnósticas, empleando tabla de contingencia de 2 x 2; ji cuadrada corregida de Yates, exacta de Fisher y la razón de posibilidad para estimar la significancia de la asociación de factores bióticos y abióticos. RESULTADOS: La seroprevalencia fue de 4 por ciento en la población humana estudiada y de los reservorios (equinos, porcinos y caninos), sólo 10 por ciento de los caninos resultaron reactivos. Los vectores identificados fueron T barberi y T pallidipennis, con índice de dispersión e índice de colonización de 55 y 40 por ciento, respectivamente. Los factores de riesgo más importantes fueron la altitud (>2 150 y <2 180 metros sobre el nivel del mar), los años de residencia, el pertenecer a un programa de asistencia social, la presencia de triatóminos y la edad. CONCLUSIONES: En localidades ubicadas a una altitud mayor a los 2 000 metros sobre el nivel del mar se reconocieron vectores infectados con T cruzi, casos humanos y probablemente reservorios domésticos.