Preparation and evaluation of aminopropyl-functionalized manganese-loaded SBA-15 for copper removal from aqueous solution.

A novel material, aminopropyl-functionalized manganese-loaded SBA-15 (NH2-Mn-SBA-15), was synthesized by bonding 3-aminopropyl trimethoxysilane (APTMS) onto manganese-loaded SBA-15 (Mn-SBA-15) and used as a Cu2+ adsorbent in aqueous solution. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction spectra (XRD), N2 adsorption/desorption isotherms, high resolution field emission scanning electron microscopy (FESEM) and X-ray photoelectron spectroscopy (XPS) were used to characterize the NH2-Mn-SBA-15. The ordered mesoporous structure of SBA-15 was remained after modification. The manganese oxides were mainly loaded on the internal surface of the pore channels while the aminopropyl groups were mainly anchored on the external surface of SBA-15. The adsorption of Cu2+ on NH2-Mn-SBA-15 was fitted well by the Langmuir equation and the maximum adsorption capacity of NH2-Mn-SBA-15 for Cu2+ was over two times higher than that of Mn-SBA-15 under the same conditions. The Elovich equation gave a good fit for the adsorption process of Cu2+ by NH2-Mn-SBA-15 and Mn-SBA-15. Both the loaded manganese oxides and the anchored aminopropyl groups were found to contribute to the uptake of Cu2+. The NH2-Mn-SBA-15 showed high selectivity for copper ions. Consecutive adsorption-desorption experiments showed that the NH2-Mn-SBA-15 could be regenerated by acid treatment without altering its properties.

Reduction of sulfur oxides emissions via adsorptive desulfurization of transportation fuels using novel silica-based adsorbent.

Transportation fuels with high sulfur content are one of the primary contributors to air pollution because they emit massive quantities of sulfur oxides upon combustion. The emitted sulfur oxides undoubtedly contribute to global warming and climate change. Therefore, they should be minimized. The current study accurately describes a novel and direct synthetic pathway for the incorporation of sulfonic acid groups (-SO3H) into mesoporous silica surface. The structure of the prepared materials was confirmed using FTIR, SEM, BET, SA-XRD, TEM, and TGA techniques. The batch adsorption technique was used to carefully evaluate the adsorption efficiency of the prepared adsorbent towards dibenzothiophene (DBT). At optimal adsorption conditions, a maximum adsorption capacity of 75-mg DBT/g adsorbent was achieved. The desulfurization process fitted well to Langmuir and pseudo-second-order models. In addition, the desulfurization process was found to be a spontaneous and exothermic process. As a final point, the practical applicability of the prepared adsorbent, as well as its reusability, was properly investigated, and the results were promising.

Ordered mesoporous silicas for potential applications in solid vaccine formulations

In an effort to develop efficient vaccine formulations, the use of ordered mesoporous silica (SBA-15) as an antigen carrier has been investigated. SBA-15 has required properties such as high surface area and pore volume, including narrow pore size distribution to protect antigens inside its matrix. This study aimed to examine the impact of solvent removal methods, specifically freeze-drying and evaporation on the intrinsic properties of an immunogenic complex. The immunogenic complexes, synthesized and incorporated with BSA, were characterized by various physicochemical techniques. Small Angle X-ray Scattering measurements revealed the characteristic reflections associated to pure SBA-15, indicating the preservation of the silica mesostructured following BSA incorporation and the formation of BSA aggregates within the macropore region. Nitrogen Adsorption Isotherm measurements demonstrated a decrease in surface area and pore volume for all samples, indicating that the BSA was incorporated into the SBA-15 matrix. Fluorescence spectroscopy evidenced that the tryptophan residues in BSA inside SBA-15 or in solution displayed similar spectra, showing the preservation of the aromatic residues’ environment. The Circular Dichroism spectra of BSA in both conditions suggest the preservation of its native secondary structure after the encapsulation process. The immunogenic analysis with the detection of anti-BSA IgG did not give any significant difference between the non-dried, freeze-dried or evaporated groups. However, all groups containing BSA and SBA-15 showed results almost three times higher than the groups with pure BSA (control group). These facts indicate that none of the BSA incorporation methods interfered with the immunogenicity of the complex. In particular, the freeze-dried process is regularly used in the pharmaceutical industry, therefore its adequacy to produce immunogenic complexes was proved Furthermore, the results showed that SBA-15 increased the immunogenic activity of BSA.

Evaluation of tumor growth remission in a murine model for subcutaneous solid tumors, benefits of associating the antitumor agent crotamine with mesoporous nanosilica particles to achieve improved dosing frequency and efficacy

Crotamine is a highly cationic polypeptide first isolated from South American rattlesnake venom, which exhibits affinity for acidic lysosomal vesicles and proliferating cells. This cationic nature is pivotal for its in vitro cytotoxicity and in vivo anticancer actions. This study aimed to enhance the antitumor efficacy of crotamine by associating it with the mesoporous SBA-15 silica, known for its controlled release of various chemical agents, including large proteins. This association aimed to mitigate the toxic effects while amplifying the pharmacological potency of several compounds. Comprehensive characterization, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis, confirmed the successful association of crotamine with the non-toxic SBA-15 nanoparticles. The TEM imaging revealed nanoparticles with a nearly spherical shape and variations in uniformity upon crotamine association. Furthermore, DLS showed a narrow unimodal size distribution, emphasizing the formation of small aggregates. Zeta potential measurements indicated a distinct shift from negative to positive values upon crotamine association, underscoring its effective adsorption onto SBA-15. Intraperitoneal or oral administration of crotamine:SBA-15 in a murine melanoma model suggested the potential to reduce the frequency of crotamine doses without compromising efficacy. Interestingly, while the oral route enhanced the antitumor efficacy of crotamine, pH-dependent release from SBA-15 was observed. Thus, associating crotamine with SBA-15 could reduce the overall required dose to inhibit solid tumor growth, bolstering the prospect of crotamine as a potent anticancer agent.

Evaluation of tumor growth remission in a murine model for subcutaneous solid tumors, benefits of associating the antitumor agent crotamine with mesoporous nanosilica particles to achieve improved dosing frequency and efficacy

Crotamine is a highly cationic polypeptide first isolated from South American rattlesnake venom, which exhibits affinity for acidic lysosomal vesicles and proliferating cells. This cationic nature is pivotal for its in vitro cytotoxicity and in vivo anticancer actions. This study aimed to enhance the antitumor efficacy of crotamine by associating it with the mesoporous SBA-15 silica, known for its controlled release of various chemical agents, including large proteins. This association aimed to mitigate the toxic effects while amplifying the pharmacological potency of several compounds. Comprehensive characterization, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis, confirmed the successful association of crotamine with the non-toxic SBA-15 nanoparticles. The TEM imaging revealed nanoparticles with a nearly spherical shape and variations in uniformity upon crotamine association. Furthermore, DLS showed a narrow unimodal size distribution, emphasizing the formation of small aggregates. Zeta potential measurements indicated a distinct shift from negative to positive values upon crotamine association, underscoring its effective adsorption onto SBA-15. Intraperitoneal or oral administration of crotamine:SBA-15 in a murine melanoma model suggested the potential to reduce the frequency of crotamine doses without compromising efficacy. Interestingly, while the oral route enhanced the antitumor efficacy of crotamine, pH-dependent release from SBA-15 was observed. Thus, associating crotamine with SBA-15 could reduce the overall required dose to inhibit solid tumor growth, bolstering the prospect of crotamine as a potent anticancer agent.

Adjuvant effect of mesoporous silica SBA-15 on anti-diphtheria and anti-tetanus humoral immune response

Routine immunization against diphtheria and tetanus has drastically reduced the incidence of these diseases worldwide. Anti-diphtheria/tetanus vaccine has in general aluminum salt as adjuvant in its formulation that can produce several adverse effects. There is a growing interest in developing new adjuvants. In this study, we evaluated the efficiency of SBA-15 as an adjuvant in subcutaneous immunization in mice with diphtheria (dANA) and tetanus (tANA) anatoxins as well as with the mixture of them (dtANA). The tANA molecules and their encapsulation in SBA-15 were characterized using Small-Angle X-ray Scattering (SAXS), Dynamical Light Scattering (DLS), Nitrogen Adsorption Isotherm (NAI), Conventional Circular Dichroism (CD)/Synchrotron Radiation Circular Dichroism (SRCD) Spectroscopy, and Tryptophan Fluorescence Spectroscopy (FS). The primary and secondary antibody response elicited by subcutaneous immunization of High (HIII) and Low (LIII) antibody responder mice with dANA, tANA, or dtANA encapsulated in the SBA-15 were determined. We demonstrated that SBA-15 increases the immunogenicity of dANA and tANA antigens, especially when administered in combination. We also verified that SBA-15 modulates the antibody response of LIII mice, turning them into high antibody responder. Thus, these results suggest that SBA-15 may be an effective adjuvant for different vaccine formulations.

The crotoxin: SBA-15 complex down-regulates the Incidence and Intensity of experimental autoimmune encephalomyelitis through peripheral and central actions

Crotoxin (CTX), the main neurotoxin from Crotalus durissus terrificus snake venom, has anti-inflammatory, immunomodulatory and antinociceptive activities. However, the CTX-induced toxicity may compromise its use. Under this scenario, the use of nanoparticle such as nanostructured mesoporous silica (SBA-15) as a carrier might become a feasible approach to improve CTX safety. Here, we determined the benefits of SBA-15 on CTX-related neuroinflammatory and immunomodulatory properties during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis that replicates several histopathological and immunological features observed in humans. We showed that a single administration of CTX:SBA-15 (54 μg/kg) was more effective in reducing pain and ameliorated the clinical score (motor impairment) in EAE animals compared to the CTX-treated EAE group; therefore, improving the disease outcome. Of interest, CTX:SBA-15, but not unconjugated CTX, prevented EAE-induced atrophy and loss of muscle function. Further supporting an immune mechanism, CTX:SBA-15 treatment reduced both recruitment and proliferation of peripheral Th17 cells as well as diminished IL-17 expression and glial cells activation in the spinal cord in EAE animals when compared with CTX-treated EAE group. Finally, CTX:SBA-15, but not unconjugated CTX, prevented the EAE-induced cell infiltration in the CNS. These results provide evidence that SBA-15 maximizes the immunomodulatory and anti-inflammatory effects of CTX in an EAE model; therefore, suggesting that SBA-15 has the potential to improve CTX effectiveness in the treatment of MS.

Crotoxin conjugated to SBA-15 nanostructured mesoporous silica induces long-last analgesic effect in the neuropathic pain model in mice

Neuropathic pain is a disease caused by structural and functional plasticity in central and peripheral sensory pathways that produce alterations in nociceptive processing. Currently, pharmacological treatment for this condition remains a challenge. Crotoxin (CTX), the main neurotoxin of Crotalus durissus terrificus rattlesnake venom, has well described prolonged anti-inflammatory and antinociceptive activities. In spite of its potential benefits, the toxicity of CTX remains a limiting factor for its use. SBA-15 is an inert nanostructured mesoporous silica that, when used as a vehicle, may reduce toxicity and potentiate the activity of different compounds. Based on this, we propose to conjugate crotoxin with SBA-15 (CTX:SBA-15) in order to investigate if when adsorbed to silica, CTX would have its toxicity reduced and its analgesic effect enhanced in neuropathic pain induced by the partial sciatic nerve ligation (PSNL) model. SBA-15 enabled an increase of 35% of CTX dosage. Treatment with CTX:SBA-15 induced a long-lasting reduction of mechanical hypernociception, without modifying the previously known pathways involved in antinociception. Moreover, CTX:SBA-15 reduced IL-6 and increased IL-10 levels in the spinal cord. Surprisingly, the antinociceptive effect of CTX:SBA-15 was also observed after oral administration. These data indicate the potential use of the CTX:SBA-15 complex for neuropathic pain control and corroborates the protective potential of SBA-15

Avaliação do efeito da crotoxina conjugada a sílica nanoestruturada SBA-15 na dor crônica: aspectos imunomodulatórios, anti-inflamatórios e antinociceptivos / Evaluating the effect of crotoxin conjugated nanostructured silica SBA-15 in chronic pain: immunomodulatory, antinociceptive and anti-inflammatory aspects

Chronic pain is among the most disabling and costly afflictions, has a negative effect on physical and psychological health, daily activities, employment and economic well-being, being recognised as an important healty public problematic. Chronic pain is characterized by sensorial alterations (hyperalgesia and allodynia) and other symptoms such as lethargy, depression and anxiety. These sickness behaviours with chronic pain are suggestive of a subjacent immune activity. The persistent pain is often associated with some other disease, such as multiple sclerosis [MS], an example of autoimmune disorder. MS is one of the most common neurological disorders diagnosed in young adults; this neuroinflammatory autoimmune disease have common symptoms such as, fatigue, visual impairment, sensory impairment, weakness, urinary dysfunction, spasticity, incoordination, cognitive dysfunction and pain. Despite the advances in research related to chronic pain and multiple sclerosis, the treatments still presenting great difficulties, since that the administration of pharmacos there is no complete reversal of symptoms or cure. Moreover, there are continual reports of patients suffering from their undesirable adverse effects. Therefore, it is necessary to study new drugs for the treatment of these pathologies. It is known that the crotoxin (CTX) despite the toxic effect, in low doses, presents immunomodulatory, anti-inflammatory, antitumor and antinociceptive effect, revealing its potential for the clinical treatment of several pathologies. It is also known that the nanostructured SBA-15 silica, a protective vehicle of biomolecules, may decrease toxicity and increase the immune response to distinct immunogens including vaccins. Thus, the objective of this study was to evaluate whether crotoxin, when conjugated to SBA-15, has its toxic effect reduced and its antinociceptive e immunomodulatory effect enhanced, evaluating its interference on the inflammatory response in the Partial Injury models of the Sciatic Nerve (PSNL) and Experimental Autoimmune Encephalomyelitis (EAE). The results show that the CTX:SBA-15 complex has analgesic effect in both models of chronic pain and reduces the incidence and intensity of clinical signs (motor defict) induced by the EAE model. Further, the treatment with the complex modulates neuroinflammation by reducing the expression of glial cell markers and the expression of proinflammatory cytokines in the CNS. Summarizing, the present work expands the knowledge of the effect of CTX, silica SBA-15 and complex CTX:SBA-15, showing that silica has a protective mechanism, which allows the use of oral CTX. Our data also significantly increase the possibilities of using silica, demonstrating its capacity as a protective vehicle for drugs.

A dor crônica quando comparada a outras doenças é uma das mais incapacitantes, apresentando efeito negativo sobre a saúde física e psicológica, atividades de vida diária, emprego e ao bem-estar econômico, gerando altos custos aos serviços de saúde, sendo considerado, portanto um problema de saúde pública. A dor crônica caracteriza-se por apresentar alterações sensoriais (hipernocicepção e alodinia) e outros sintomas como letargia, depressão e ansiedade, o que caracteriza uma resposta clássica de doença sistêmica e sugere atividade imune subjacente. Esta condição pode estar frequentemente associada a algumas outras doenças, como a esclerose múltipla [EM], exemplo de desordem de origem autoimune; essa é uma das doenças neurológicas mais comuns diagnosticada em jovens adultos, que desenvolvem doença autoimune neuroinflamatória. Os sintomas mais comuns incluem fadiga, déficit visual e sensorial, fraqueza, disfunções urinárias, espasticidade, problemas de coordenação motora e cognitivos, dor, entre outros. Apesar dos avanços das pesquisas relacionadas a estas doenças, o tratamento ainda apresenta grandes dificuldades, pois mesmo com a administração de fármacos não há reversão completa dos sintomas ou cura; além disso, são constantes os relatos de pacientes que sofrem com efeitos adversos indesejáveis decorrente das terapias. Assim, faz-se necessário o estudo de novas drogas para o tratamento desta doença. Sabe-se que a crotoxina (CTX) apesar do efeito tóxico, em baixas doses apresenta efeito imunomodulatório, antiinflamatório, antitumoral e antinociceptivo, revelando seu potencial para o tratamento clinico de diversas doenças. Por sua vez, a sílica nanoestruturada SBA-15 quando utilizada como veiculo protetor de biomoléculas pode diminuir a toxicidade e favorecer a resposta imunológica a diversos imunógenos, incluindo vacinas. Assim, o objetivo deste trabalho foi avaliar se a CTX, quando conjugada à sílica SBA-15, tem seu efeito tóxico diminuído e seu efeito antinociceptivo e imunomodulatório aumentado, avaliando ainda sua interferência sobre a inflamação nos modelos de Lesão Parcial do Nervo Isquiático (PSNL) e Encefalomielite Autoimune Experimental (EAE). Os resultados obtidos mostram que, o complexo CTX:SBA-15 apresenta efeito analgésico nos dois modelos de dor crônica e reduz a incidência e a intensidade dos sinais clínicos (defict motor) induzido pelo modelo de EAE. O tratamento com o complexo ainda, modula a neuroinflamaçao, reduzindo a expressão de marcadores de celulas gliais e a expressão de citocinas próinflamatótias no SNC. O presente trabalho amplia o conhecimento do efeito da CTX, da sílica SBA-15 e do complexo CTX:SBA-15, demonstrando ainda que a sílica apresenta mecanismo protetor, o que permite a utilização da CTX por via oral. Nossos dados ampliam, ainda, de maneira significativa, as possibilidades de uso da sílica, demonstrando sua capacidade como veículo protetor de fármacos.

Validação de bioensaios para o estudo da imunogenicidade da vacina contra raiva / Validation of bioassays to immunogenicity assessment of the anti-rabies vaccines

Para atestar a imunogenicidade de vacinas contra a raiva, os testes de titulação e de soroneutralização de vírus rábico em células BHK-21 foram validados, com os seguintes resultados: [a]linearidade: r= 0,99 e 1,0; [ b] precisão intra- ensaio: CV= 3,4 e 6,3 % ; [ c] precisão inter-ensaios CV = 4,7 e 5, 5 % ; [ d] estabilidade ao congelar e descongelar amostras: CV = 3,5 e 11, 7% [e] estabilidade -tempo entre o descongelamento e a realização do teste: CV = 1% ; [f] exatidão > 96% e > 87% para ambos os testes. Cinco esquemas de imunização com diferentes concentrações, vias de inoculação e intervalos entre doses foram avaliados em camundongos BALB/c com a vacina contra a raiva produzida em células Vero no Instituto Butantan...

To assure the reliability of the results of immunogenicty of raccines, tests of virus titration and neutralization in BHK -21 cells were validated, with the following results: [a] linearity r = 0,99 and 1,0 ; [b] repeatability, CV = 3,4 and 6,3 %; [ c] precision, CV = 4,7 and 5,5 %; [d] freeze- thaw stability, CV =3,5 and 11,7% ; [e], C V = 1% and [f] accuracy = > 96% and > 87% for both tests. Five schemes of immunization with different concentrations, routes of inoculation and interval between doses were evaluated in BALB/c mice with rabies vaccine in Vero cells produced at Instituto Butantan...