http://tede.unicentro.br:8080/jspui/handle/tede/565 Programa de Pós-Graduação em Ciências Farmacêuticas 2025-11-25T06:59:48Z http://tede.unicentro.br:8080/jspui/handle/jspui/1766 Título: TERAPIA TRANSCRANIANA COM LED NOS COMPRIMENTOS DE ONDA 630NM E 904NM NO MODELO DE ACIDENTE VASCULAR ENCEFÁLICO (AVE) Autor: Fonseca, Eliane Gonçalves de Jesus Primeiro orientador: Carraro, Emerson Abstract: Introduction: The cerebrovascular accident (CVA) is one of the main causes of death worldwide, as well as motor, cognitive and sensory sequelae. Several interventions have been proposed in recent years, as a way to prevent and mainly treat stroke. In this context, the treatment with Photobiomodulation (FBM) through LED (Light Emitting Diode) stands out, which indicates promising results, as it stimulates cell metabolism, increasing cell regenerative potential and promoting neurogenesis. Objective: This study aimed to evaluate the effects of 630nm LED and 904nm LED in animals submitted to ischemic stroke, analyzing the neurogenesis and motor behavior of these animals. Methodology: This is an experimental study with controlled intervention that included a sample of 75 Rattus norvegicus, Wistar, males, divided into 3 groups: a control group consisting of 15 animals without treatment, a group treated with 630nm LED and a group treated with 904nm LED , composed of 30 animals in each treated group. All animals underwent stereotaxic surgery for electrode implantation and subsequent electrolyte injury, and the results were compared at 3, 7 and 21 days of treatment after surgery. Results: In the apprehension, open field and suspension tests show improvement in the motor behavior where there was an increase in strength, endurance, locomotion and functionality and neurogenesis of the animals in both evaluated treatments, as well as histological and immunohistochemical analysis. Conclusion: The present study suggests that the treatments with 630nm LED and 904nm LED favored greater motor response and that they can be promising therapies because they are simple, inexpensive and easy to apply techniques. Instituição: Universidade Estadual do Centro-Oeste Tipo do documento: Tese 2021-08-06T00:00:00Z http://tede.unicentro.br:8080/jspui/handle/jspui/1765 Título: NANOPARTÍCULAS LIPÍDICAS SÓLIDAS DE PALMITATO DE METILA PARA CARREAMENTO DA CURCUMINA Autor: Lopes, Vanessa Falchetti Primeiro orientador: Khalil, Najeh Maissar Abstract: Solid lipid nanoparticles are considered a promising way for compounds encapsulation that show physical and chemical limitations, such as curcumin, which despite exhibiting several therapeutic applications, has a lower bioavailability after an oral administration and low solubility in physiological solutions. Therefore, the use of pharmaceutical nanotechnology as a tool to expand the physical-chemical properties of curcumin stands out. Methyl palmitate is an ethanol soluble lipid and endogenous from the metabolism, however, not yet used to obtain nanostructured systems. Thus, the goal of this study was to obtain, characterize and perform biological evaluation assays of solid lipid nanoparticles of methyl palmitate with curcumin in it. For this, a factorial design was used in order to optimize the conditions of obtaining the developed nanoparticles by the high shear homogenization method. As a result, the nanoparticles which contain curcumin presented: average diameter of 162.41 ± 5.7 nm with monomodal distribution profile; 0.10 ± 0.05 poly-dispersion index, characterizing homogeneity of the suspended particles; zeta potential of -18.00 ± 0.2 mV and 68.42% ± 0.7 of encapsulation efficiency. After the lyophilization process with mannitol (5%), the nanoparticles presented at the end of 150 days, 261.63 ± 8.75 nm, polydispersion index of 0.25 ± 0.03 and zeta potential – 19.45 ± 0.78 mV, suggesting the use of mannitol for a cryoprotection and stability of the system during storage. In addition, the nanostructured system presented, through the X ray diffraction technique, lower crystallinity index value in relation to isolated methyl curcumin and methyl palmitate and, according to the infrared spectrograms, there was no chemical interaction that could modify the characterized functional groups. The results of the thermal analysis showed that curcumin was dispersed amorphaly in the nanoparticles and the microscopy images confirmed the nanometric size. In the in vitro assays, the nanoparticles showed stability when submitted to simulated gastrointestinal fluids, protecting the molecule from pH variations and in phosphate buffer saline (PBS), 60% of the curcumin was released through the lipid matrix. The applicability of the nanoparticles was evaluated by the potential antioxidant study, and also by evaluating cytotoxicity in erythrocytes and Candida sp. Regarding the antioxidant study, the nanostructured system demonstrated a similar inhibition to free curcumin against Acid2,2'-azinobis-3-ethylbenzothiazolin-6-sulphonic (ABTS●+). Cytotoxicity on erythrocytes was higher with free curcumin than with the nano-encapsulated. The anti-fungal activity of the nanoparticles was dose-dependent, with minimal inhibitory concentration (MIC50) at 7.5 μg.mL-1 under all tested strains. In the pharmacokinetic assay, a significant improvement was observed in the pharmacokinetic parameters of curcumin when nano-encapsulated to, after oral single-dose administration in mice. The amount of curcumin available in plasma was higher when transmitted in the nanoparticles (AUC0-t = 117.85 ± 10,63 ng.h/mL-1) compared to the free molecule (AUC0-t = 34.36 ± 13,76 ng.h/mL-1) and the bioavailability of curcumin in the nanoparticles was three times higher than that presented by the free molecule. Finally, the results of this unprecedented study indicate that methyl palmitate can be used in the development and application of oral lipid nanoparticles, and that the system has the potential to improve curcumin bioavailability. Instituição: Universidade Estadual do Centro-Oeste Tipo do documento: Tese 2021-06-24T00:00:00Z http://tede.unicentro.br:8080/jspui/handle/jspui/1764 Título: INOVAÇÃO INCREMENTAL NO TRATAMENTO DE LESÕES HERPÉTICAS: DESENVOLVIMENTO DE CREME CONTENDO PENCICLOVIR E LISINA Autor: Meira, Rafaela Zielinski Cavalheiro de Primeiro orientador: Oliveira, Paulo Renato de Abstract: Infections caused by the herpes simplex virus (HSV) are very common, with large medical and epidemiological importance. Among the viral species, HSV-1 has higher seroprevalence, and is typically transmitted during childhood through the orofacial route. Penciclovir is among the most used drugs for the prophylaxis and topical treatment of this infection. The number of drugs for anti-herpetic treatment is still limited, in addition to the increased incidence of viral resistance to existing ones. Innovative drugs require a lot of investment and a lot of time to enter the market, so a new strategy is in the refinement of already known and used assets, either in their molecules or in the face of already commercialized formulations, the explored incremental innovation. Special attention was given to lysine, an important antiviral agent that has been indicated for the prophylaxis and treatment of herpetic lesions, especially orofacial lesions, by oral administration, together with classic drugs. Recent studies idealizing the use of lysine in formulations for this purpose, associated or not with another active, are unknown, a fact that led us to consider the development of a cream that combines penciclovir with lysine as a possible innovative formula. In vitro analyzes of the assets showed synergistic antiviral action between them, with a reduction in the IC50 of the drugs when combined. With this observation, it followed with the pharmacotechnical development of the formulation, based on the study of compatibility between drugs and excipients, as well as on important tests in the evaluation of properties of the final product. The excipients chosen to form part of the formulation were paraffin, sodium lauryl sulfate, ceto-stearyl alcohol, propylene glycol and liquid petroleum jelly. The cream showed pseudoplastic behavior, characteristic of pharmaceutical creams. There was no growth of microorganisms in microbiological analyzes, revealing their quality and safety in the presence of a good preservative system. For the evaluation of the stability and also of the permeation of the drugs using Franz Cell, analytical methodologies by HPLC were developed and validated. The stability of the product was proven with the unchanged drug contents and penciclovir has been shown to permeate equally in formulations with and without the presence of lysine. Animal model experimentation converged with the objectives of the study, since the formulation that combines these two actives showed much faster action than the creams that presented them alone. On the third day of treatment, the group treated with the cream proposed in this study has already matched the negative control group, whereas this result can only be obtained on the seventh day by the group treated with the cream that contained only penciclovir. The idealized and developed formulation: a cream, safe and effective, containing penciclovir and lysine, then becomes an incremental innovation in the treatment of herpetic lesions (patent filing process number: BR 10 2020 014414 6). Instituição: Universidade Estadual do Centro-Oeste Tipo do documento: Tese 2021-09-30T00:00:00Z http://tede.unicentro.br:8080/jspui/handle/jspui/1763 Título: EFEITOS DA ASSOCIAÇÃO ENTRE GEL DE Cecropia glaziovii E LED 627nm NA CICATRIZAÇÃO DE LESÕES CUTÂNEAS POR SEGUNDA INTENÇÃO Autor: Suckow, Patricia Pacheco Tyski Primeiro orientador: Oliveira, Paulo Renato de Abstract: Healing is a complex and dynamic process that can be divided into phases with the aim of restoring damaged tissue and returning homeostasis. Pathologies that increase healing time can generate huge expenses with treatments and evidence the search for drugs and therapies capable of reacting with the injury, aiming to accelerate tissue repair. The use of photobiomodulation can be effective in tissue healing, with emphasis on the use of LED in tissue repair. Cecropia glaziovii SNETH, popularly known as “embaúba”, is a native species of Latin America, where it is used in different ways. In general, Cecropia is popularly used for the treatment of respiratory problems, such as cough, asthma and bronchitis, systemic arterial hypertension, diabetes and inflammatory processes, in addition to being used as a diuretic and cardiotonic. It has, in its chemical composition, bioactive compounds with anti-inflammatory and antioxidant activities. In this context, the present study aimed to verify the effects of 627nm LED and Cecropia glaziovii gel as isolated treatment and the association of the two treatments in the healing process in an experimental model. For this, a 3% sodium carboxymethylcellulose gel containing Cecropia glaziovii extract at 5% concentration was developed; the chosen concentration of the polymer was the ideal one to achieve the desired spreadability of the product as it had the best viscosity. Cecropia glaziovii gel was applied to the lesion before irradiation with 627nm LED. The in vivo evaluation was performed using a dorsal punch model, and the sample consisted of 96 Rattus Norvegicus rats, Wistar lineage, divided into 4 groups. Positive Control (CP), 627nm LED (LED), LED associated with Cecropia (LED+CEC) and Cecropia (CEC). All groups were analyzed at 3, 7, 14 and 21 days. The analyzes performed were: histological and histomorphometric, immunohistochemistry, flow cytometry, collagen by polarized light and macroscopic analysis. The collected data were analyzed statistically. It was observed that all treatment modalities presented good results, however, each one proved to be more adequate in different periods. Treatment with Cecropia glaziovii gel alone was superior in the first 7 days after the injury. The treatment using the association LED and Cecropia glaziovii gel showed greater potential between 7 and 14 days. And finally, the treatment with only LED was superior to the others in the last days of the process, between 14 and 21 days. It was concluded that the 3 types of treatment are promising for therapeutic applicability in healing processes, and given the results obtained, a more appropriate therapeutic protocol can be suggested as follows: daily application of Cecropia glaziovii gel in the first 7 days after the injury , daily application of the gel associated with 627nm LED irradiation between 7 and 14 days, and application of LED only between 14 and 21 days to complete the treatment. Instituição: Universidade Estadual do Centro-Oeste Tipo do documento: Tese 2021-06-30T00:00:00Z