GUSTAVO HENRIQUE COSTAVARCA

GUSTAVO HENRIQUE COSTAVARCA

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Solubility study of Kraft lignin for the development of electrospun nanofibers
2022 - NOGUEIRA, K.M.; VARCA, J.O.; LIMA, C.S.; CRUZ, C.C. da; RIBEIRO, A.H.; FREITAS, L.F.; VARCA, G.H.; LUGAO, A.B.
Lignin is a high-volume byproduct of paper manufacturing which has been explored in many research fields, especially for the development of fiber and nanofiber for biomedical applications [1,2]. This work presents a solubility study performed through gravimetry for kraft lignin considering its application for the development of electrospun nanofibers [3]. In practical terms, lignin was solubilized in alkaline aqueous solution, dimethylformamide and dimethylsulfoxide, at concentrations of 10, 15 and 20% (w/v) and varying temperatures of 25, 50 and 75 ºC, under constant stirring. After solubilizing, the solution was filtered, and the insoluble fraction was dried in the oven at 100 ºC. At 25 ºC lignin was insoluble in all solvents tested, as predicted using Hansen solubility parameters. Although the increase in temperature promoted lignin solubilization in all solvents tested, at the highest temperature assayed, the solubilization was facilitated, presenting the smallest levels of the insoluble fraction. Lignin was soluble in all solvents tested, and optimum solubility conditions were achieved using 10% lignin solutions (w/v), without significant insoluble fraction, and therefore ideal concentration for the development of lignin based fibers.
A biological study of gelatin-PVA based scaffold functionalized with albumin for biomedical purposes
2022 - VARCA, J.O.; KLINGBEIL, F.; NOGUEIRA, K.M.; LIMA, C.S.; CRUZ, C.C. da; FREITAS, L.F.; VARCA, G.H.; MATHOR, M.B.; LUGAO, A.B.
Biomaterials have been designed for tissue reconstruction, bone regeneration and cell culture, and functionalized with presence of proteins, nanoparticles, peptides and other components to improve the biocompatibility for instance. This work shows a biological study of gelatin-PVA based scaffold with controlled pore size and functionalized with albumin for biomedical purposes. The in vitro study comprises cytotoxicity, cell adhesion and proliferation assessment. In practical terms, the gelatin-PVA scaffold crosslinked and sterilized by gamma radiation followed by freeze-drying was evaluated by cytotoxicity, adhesion and proliferation tests. The cytotoxicity results showed that the biomaterial produced was non-toxic, and adhesion and proliferation assays showed that the material was suitable for tissue engineering. The presence of albumin did not present a significant impact on the cell performance, at the assayed concentration.
Géis mucoadesivos para o tratamento do câncer de bexiga superficial
2022 - LIMA, C.S.; HERMIDA, M.R.; VARCA, G.C.; FREITAS, L.F.; LORENZO, C.A.; LUGAO, A.B.
A mucoadesividade tem sido estudada na área farmacêutica há mais de 50 anos e é uma propriedade explorada para aumentar o tempo de residência de um fármaco, bem como para melhorar a especificidade da entrega do ativo ao local desejado. Um sistema mucoadesivo que permite a absorção direta do fármaco e uma diminuição da taxa de excreção, consequentemente, tem-se uma maior biodisponibilidade do ativo associada à administração de doses menores, com menor frequência (Yan et al., 2017). O câncer de bexiga (CB) é uma das principais doenças que atacam o trato urinário e se dá pela proliferação anormal das células do tecido da parede interna da bexiga conhecida como urotélio (INCA, 2021). Sabe-se que o tratamento por quimioterapia intravesical do CB apresenta algumas limitações como a permeação do ativo no urotélio e o tempo de residência desse fármaco que é muito limitado devido ao efeito de diluição e lavagem da urina que acaba eliminando-o completamente. Dessa forma, o desenvolvimento de novos veículos mucoadesivos para o carreamento da quimioterapia pode ser uma opção de tratamento avançado (Kolawole et al., 2017). Neste trabalho, buscou-se preparar géis mucoadesivos a partir da goma gelana (0,1% m/v) e de uma blenda de carboximetilcelulose (2% m/v) e polivinil álcool (0,2% m/v), contendo um adjuvante para aumento de permeação (papaína), como potenciais alternativas para a quimioterapia intravesical. Foram realizados ensaios de reologia (frequency sweep para avaliação dos módulos de perda (G’’) e de armazenamento (G’)); força de adesão para estudo da capacidade de mucoadesão das formulações e, por fim, de citotoxidade em duas linhagens celulares, HUVEC (endotelial humana) e V79-4 (fibroblastos) . Os ensaios reológicos dos géis apresentam resultados característicos de comportamentos pseudoplásticos, isto é, com maior fluidez a altas frequências, e, portanto, com potencial para aplicação por seringa e cateter. Os ensaios de mucoadesão confirmaram que os polímeros escolhidos apresentam capacidade de interação com a mucina presente no urotélio, representando alternativas interessantes para o aumento do tempo de residência e da biodisponibilidade da terapia. Por fim, as formulações apresentaram pouca ou nenhuma toxicidade, mostrando potencial para aplicação biomédica.
Antimicrobial activity and physicochemical performance of a modified endodontic sealer
2020 - GONCALVES, FLAVIA; CAMPOS, LUIZA M. de P.; SANCHES, LUCIANA K.F.; SILVA, LARISSA T.S.; SANTOS, TAMIRIS M.R. dos; VARCA, GUSTAVO H.C.; LOPES, DIANA P.; COGO-MULLER, KARINA; PARRA, DUCLERC F.; BRAGA, ROBERTO R.; SANTOS, MARCELO dos; BOARO, LETICIA C.C.
Introduction: this study aimed to evaluate the antimicrobial and physicochemical properties of a commercial endodontic sealer modified by the addition of montmorillonite (MMT) nanoparticles loaded with two different drugs: chlorhexidine (CHX) or metronidazole (MET). Methods: 5 wt% MMT/CHX or MMT/MET nanoparticles were added to the sealer AH-Plus. The experimental materials were evaluated for drug release, antimicrobial activity, flow, flexural strength, and flexural modulus. Data were subjected to one-way ANOVA, Kruskal-Wallis, and Mann-Whitney tests. Results: The drug incorporation into MMT particles was 9% and 10% for CHX and MET, respectively. At 20 days after manipulation, 16.5% of the drug was released by the sealer with MMT/MET and 0.4% by MMT/CHX. The addition of both nanoparticles decreased the flow of materials, but they were still in compliance with ISO 6876-2012. The conversion, flexural strength, and flexural modulus of MMT/MET (87%, 37±7 MPa, 2.3 GPa) and MMT/CHX (78%, 29±2 MPa, 2.7 GPa) were similar in both groups but lower than in the control group (100%, 54±7 MPa, 4.0±0.7 GPa). Both experimental materials were able to form an inhibition halo for E. faecalis bacteria (CHX: 4.8±1.4 and MET: 4.0±1.6 mm), whereas the control group did not inhibit the microorganism. Conclusion: both formulations proposed as endodontic sealer presented effective antimicrobial activity and acceptable flow. The addition of MMT/CHX and MMT/MET particles decreased the conversion and mechanical properties, but further studies are required to clarify the clinical relevance of these properties.
The effect of radiation dose rate over the formation of protein-based nanoparticles for nanosized delivery of chemo and radiotherapeutics
2018 - VARCA, G.H.C.; FAZOLIN, G.N.; FERREIRA, A.H.; OLIVEIRA, J.P.R. de; MARQUES, F.; LUGAO, A.B.
Recent studies demonstrated the development of papain and bovine serum albumin nanoparticles using gamma radiation (10 kGy) in presence of 20-30% (v/v) ethanol. With the purpose of producing stable and well defined nanocarriers, this work aims to determine the influence of different dose rates over protein nanoparticle formation. For this purpose, papain and BSA nanoparticles were synthetized in phosphate buffer (50 mM, pH 7.2) and ethanol (20-30%, v/v) using a radiation dose of 10 kGy and dose rate of 0.8, 2, 5 and 10 kGy.h-1. After irradiation, samples were evaluated by dynamic light scattering, fluorescence and proteolytic activity to verify the size, secondary structure and monitoring of the enzymatic activity, respectively. For papain nanoparticles it was observed that the dose rate did not influence the particle size formation, however crosslinking evidenced by bityrosine showed that samples irradiated at 0.8 and 5 kGy.h-1 presented higher bityrosine levels. On the other hand, BSA nanoparticles presented different results if compared to papain NPs. Different dose rates caused different and non-linear size increase for each condition, following the order: 5 > 10 > 0.8 > 2 kGy.h-1. However, in terms of crosslinking formation, a linear increase was registered, as at 0.8 kGy.h-1 the smallest signal was achieved, whereas at 10 kGy.h- 1 the highest signal was recorded. In conclusion, BSA nanoparticles were more sensitive to different radiation dose rates than nanopapain. Optimized results in terms of size increase and higher bityrosine levels were observed for the samples irradiated at 5 kGy.h-1, in which nanoparticle formation will occur faster if compared to the synthesis carried out under distinct conditions. As final applications of the system concert their use for the delivery of chemo or radiotherapeutics, the loading of paclitaxel, a well-known chemotherapeutic agent, and radiolabeling with tecntetium- 99m, a radioisotope suitable for biomedical applications, have also been performed with high efficiency, thus demonstrating a proof of concept of such systems.
Desenvolvimento de nanocarreadores bioativos na forma sólida à base de papaína induzidas por radiação
2018 - FAZOLIN, G.N.; VARCA, G.H.C.; LUGAO, A.B.
A papaína, enzima proteolítica extraída do látex do fruto verde do mamão papaia adulto, é um produto de interesse médico por possuir características importantes como auxiliar na redução do crescimento bacteriano em escaras além de possuir alta bioatividade e ser um produto com potencial para carreamento de fármacos. Recentemente desenvolvida em nano escala, a nanopartícula de papaína foi sintetizada utilizando a técnica de síntese por radiação a fim de promover reticulação intermolecular e esterilização do meio, simultaneamente. Contudo, a papaína em meio aquoso sofre hidrolise e por este motivo sua aplicação como nanocarreador pode ser dificultada. Visando a utilização da nanopartícula de papaína como nanocarreador de fármacos, se faz necessário a obtenção da nanopartícula na forma sólida. Este trabalho tem o objetivo de estudar o comportamento das nanopartículas de papaína congeladas e liofilizadas além de sua estabilidade frente ao tempo. A síntese foi realizada utilizando tampão fosfato 50 Mm pH 7,4 e etanol como cosolvente, além de induzir a reticulação com radiação ionizante utilizando a dose de 10 kGy e taxa de dose de 5 kGy.h-1. Após a síntese e irradiação, as amostras foram congeladas a - 80ºC. O tamanho e a estrutura secundária foram avaliados através das técnicas de espalhamento dinâmico de luz e fluorescência, a atividade enzimática foi analisada utilizando substrato específico. A amostra de papaína nativa possui tamanho médio de 4 nm e a nanopapaína ± 7 nm, contudo, após a liofilização, observou-se que os tamanhos não são mantidos, apresentando ± 4 nm para ambas as amostras. Os rendimentos das amostras foram superiores a 90% para todas as condições e considerados satisfatórios. Utilizando açúcares como trehalose e beta-ciclodextrina (2% v/v), este rendimento subiu para 96-98%, porém, a bioatividade caiu cerca de 30% após liofilização e 40% nas amostras liofilizadas com açúcar, ou seja, o dobro do esperado. Sendo assim, concluiu-se que o uso do açúcar é satisfatório no aumento do rendimento porem é indispensável na concentração estudada.
Development of mucoadhesive PVA/CMC based hydrogel for intravesical chemotherapy
2018 - LIMA, C.S.A.; VARCA, J.O.; FERRARI, A.; NOGUEIRA, K.M.; VARCA, G.H.C.; LUGAO, A.B.
Bladder cancer (BC) is one of the main diseases that attack the urinary tract and is globally responsible for 165,000 deaths per year. Bladder tumor may be classified as non-muscle invasive (superficial) or muscle invasive. About 70% of patients present the superficial bladder cancer which is treated by transurethral resection for tumor removal followed by intravesical chemo or immunotherapy. The main challenge reported in the instillation of chemotherapy is the limited drug residence time in the bladder as a consequence of urine levels that leads to fast drug removal from the bladder.1 Hydrogels are chemically or physically crosslinked polymer systems that form three-dimensional networks with high water absorption capacity. Carboxymethylcellulose (CMC) is one of the major soluble derivatives of cellulose widely applied in the medical and pharmaceutical fields due to its biocompatibility, nontoxicity, biodegradability and film forming ability.2 Polyvinyl Alcohol (PVA) is a synthetic polymer with wide pharmaceutical and biomedical applications as it is nontoxic, non-carcinogenic, bioadhesive and easy to process.3 In this work, we developed a mucoadhesive hydrogel from a CMC and PVA polymer blend for chemotherapeutic loading and suitable rheological properties for intravesical instillation, especially designed for treating superficial BC with increased residence time of chemotherapeutic agent. Three formulations (C1, C2 and C3) at different CMC concentrations were prepared - 1%, 2% and 3% (w/v), respectively. PVA concentration corresponded to 1% (w/v) for all formulations. The polymers were separately solubilized in Milli-Q water and then mixed prior to the addition of 20% (v/v) glycerin to increase the mucoadhesiveness of the material. The hydrogels were characterized according to their organoleptic and rheological properties to evaluate the behavior of the material under tension and temperature. Accelerated stability tests of the pharmaceutical form were also performed. Comparatively, formulations with glycerin presented improved mucoadhesiveness, and formulations with 1 and 2% of CMC presented more adequate rheological behavior for the proposed application. In conclusions, the systems presented adequate properties for the delivery of chemotherapeutic agents for optimized BC treatments.
Development of lignin-PVP based dressing for wound treatment
2018 - NOGUEIRA, K.M.; VARCA, J.O.; VARCA, G.H.C.; LIMA, C.S.A.; LUGAO, A.B.
Lignin is a carbon renewable source and has been widely explored in different fields in the last years, especially in biomaterials as dressing and other biomedical devices due its natural origin and low cost1. Poly(ethylene oxide) (PEO) is a synthetic polymer largely used in biomedical applications due its important characteristics such as high hydrophilicity, non-toxicity and ease of process2. The present work aimed to develop a lignin-PEO based dressing for wound treatment by casting. In specific terms, three different polymer blends were formulated using a range of 3 to 10% (w/v) lignin was tested with the addition of 1 to 3% PEO. Lignin was solubilized in aqueous solution (pH>13) alkalized with sodium hydroxide and PEO was solubilized in distilled water. The solutions were heated up to 70 ºC and homogenized until complete polymer dissolution. Then, PEO solution and poly(ethylene glycol) diacrylate (PEGDA) (0.5 - 1.0%) were added to the lignin solution and the blend was mixed for 30 minutes at 70 ºC. Posteriorly the blends were submitted to casting and drying under different conditions, room temperature for 48 hours and incubated at 40 ºC for 24 hours. A control sample of 6% lignin was prepared in the same conditions. Samples were evaluated by physico-chemical and morphological characterizations. The swelling and gel fraction profiles were assessed as well as thermal behavior by differential scanning calorimetry. Chemical modifications were evaluated by infrared spectroscopy. Samples with higher PEGDA content presented minor swelling index. The blends formulated presented different thermal behavior in comparison with the control. Infrared spectroscopy pointed some chemical modifications promoted by the crosslinking agent. In general terms, the material developed presented a potential to continue been explored as dressing for wound treatment
Influência do cosolvente na formação de nanopartículas de papaína induzidas por radiação
2018 - FAZOLIN, G.N.; VARCA, G.H.C.; LUGAO, A.B.
Biomateriais à base de proteínas são de grande interesse biomédico e vem mostrando relevância nas linhas de pesquisas atuais por serem uma alternativa no carreamento de fármacos, além de apresentar efeitos colaterais reduzidos ou inexistentes. A papaína, enzima proteolítica utilizada neste trabalho, é uma alternativa no estudo de sistemas nano estruturados por se mostrar promissora no carreamento de fármacos. A técnica utilizada para síntese desta nanopartícula utiliza o etanol como cosolvente. Além de promover desolvatação na proteína, o etanol tem a função de proteger a enzima durante o processo de radiação – utilizado para reticulação e esterilização. Observou-se anteriormente que o etanol auxilia no aumento do tamanho da nanopartícula, contudo, não se sabe qual a influência deste cosolvente durante o processo. Sendo assim, o objetivo principal deste trabalho é estudar a influência do etanol nas nanopartículas de papaína. A síntese será realizada na presença (20%) e ausência do etanol, tampão fosfato 50 Mm pH 7,4 e radiação ionizante a 10 kGy durante 2 horas (5 kGy/hora). As amostras foram avaliadas através da técnica de espalhamento dinâmico de luz, fluorescência e bioatividade a fim de verificar o tamanho, a estrutura secundária e acompanhamento da atividade enzimática, respectivamente. Após a irradiação, as amostras foram filtradas, congeladas e liofilizadas por 48 horas. As amostras foram resuspendidas em duas condições: água deionizada e na presença de etanol. Observou-se quando resuspendidas em água, as amostras voltam ao tamanho nativo (± 4 nm) enquanto na presença de etanol este tamanho é mantido como no controle (± 7 nm). As análises de fluorescência demonstraram que a reticulação por radiação continuou existente e a bioatividade decaiu 30% em ambos os casos, quando comparada com a bioatividade inicial. Conclui-se que o etanol contribui para a formação do tamanho da nanopartícula durante a síntese porem quando evaporado perde-se a solvatação e mantem o aumento de tamanho somente promovido pela radiação.
In vitro and in vivo toxicity evaluation of resveratrol assisted gold nanoparticles
2017 - BARROS, JANAINA A.G.; MAZIERO, JOANA S.; MAMEDE, FERNANDA C.S.; CAVALCANTE, ADRIANA K.; ROGERO, SIZUE O.; BATISTA, JORGE G.S.; VARCA, GUSTAVO H.C.; ROGERO, JOSE R.; LUGAO, ADEMAR B.
Gold nanoparticles (AuNP) are being investigated for diagnostic and therapeutic nanomedicines considering their low toxicity and stability against oxidation, among other features. The increasing production and use of AuNP can result in release of them into aquatic environment and the impacts on the aquatic organisms are not clear and the safety of AuNPs are still under investigation. This work aimed analyze the toxicity of resveratrol assisted AuNP synthesized in buffer phosphate pH 7.0 with approximately 47 nm in DLS and 15 nm in TEM analysis and gold ionic solution (Au+3). Cytotoxicity by neutral red uptake method and acute ecotoxicological assay on Daphnia similis were used. AuNP presented no cytotoxicity up to 246 mg L-1 while Au+3 showed IC50=7.95 mg L-1. AuNP CE50 was 113.15 mg L-1 and for Au+3 0.05 mg L-1. More studies can be conducted for the determination of safety ionic Au+3 and AuNP concentrations in aquatic environment.