Doutorado em Nanotecnologia Farmacêutica em Rede (FF)
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Item Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade(Universidade Federal de Goiás, 2023-04-04) Guerra, Maria Carolina Andrade; Fialho, Sílvia Ligório; http://lattes.cnpq.br/6277013725246341; Cunha Júnior, Armando da Silva; http://lattes.cnpq.br/8278273904187275; Cunha Júnior, Armando da Silva; Lima, Eliana Martins; Dias, Marina França; Dourado, Lays Fernanda Nunes; Fialho, Silvia LigórioAge-related macular degeneration, AMD, is a chronic eye disease which damages the macular area. It is the main cause of adult blindness worldwide. The pharmacological treatment of choice for the neovascular form of AMD consists of intravitreal injections of anti-VEGF agents that, occasionally, might be combined with corticosteroids. Intravitreal injections are the preferred route for drug delivery to the posterior segment of the eye but have limited therapeutic success due to the quick elimination of substances, requiring frequent injections that bring complications to the patient and low adherence to treatment. Intravitreal implants are capable to maintain therapeutic levels of drugs for a long period. Biodegradable nanofibers can modulate drug release in addition to allowing the incorporation of fragile bioactive substances. The present work aimed the development of biodegradable intravitreal implants containing dexamethasone coated with polymeric nanofibers containing bevacizumab as a therapeutic proposal for the treatment of AMD. Nanocoated implants were successfully developed. The characterization of the system, the study of degradation and efficiency of the coating process were evaluated by scanning electron microscopy. The drug release profile was determined by high performance liquid cromatography and the Bradford method. The antiangiogenic activity was determined by the chicken embryo chorioallantoic membrane model. The safety of the formulation was evaluated in rabbit eyes. So far, the system was successfully developed. The study degradation study confirmed the presence of nanofibers on the implant surface for up to 35 days. The degradation study demonstrated the presence of nanofibers on the surface of the implant for up to 35 days. The release profile showed that 68% of dexamethasone was released within 35 days and 90% of bevacizumab within 48 hours. The formulation presented activity in reducing vessels and was safe for the rabbits’ retina. No clinical or histopathological changes were observed, neither alteration in retinal thickness by optical coherence tomography during the 28 days. The developed implants, therefore, may be considered as a new alternative for the treatment of AMD.Item Obtenção, caracterização e avaliação pré-clínica da segurança de nanopartículas lipídicas e poliméricas contendo o antiangiogênico sunitinibe para aplicação tópica ocular: um estudo comparativo(Universidade Federal de Goiás, 2014-06-27) Souza, Leonardo Gomes; Lima, Eliana Martins; http://lattes.cnpq.br/7248774319455970; Lima, Eliana Martins; Gremião, Maria Palmira Daflon; Cunha Júnior, Armando da Silva; Isaac, David Leonardo Cruvinel; Marreto, Ricardo NevesCorneal vascularization (CV) is a common cause of visual impairment and blindness. Sunitinib (SUB) is an antiangiogenic agent that has demonstrated a significant reduction of VC in rabbits. Incorporation of SUB in nanosystems can increase your corneal retention and decrease P-glycoprotein resistance and it conversion to inactive isomer E (trans) when the drug is exposed to light. In this work, liposomes (LIPO), polymeric nanospheres (NE) and solid lipid nanoparticles (SLN) containing SUB was developed. Systems presented particle size between 70 and 200 nm and PdI below 0.3 and a high encapsulation efficiency. NE had a greater capacity to incorporate sunitinib when compared to liposomes and SLN. This system had drug loading of 4.3% while LIPO and SLN showed 2.87% and 1.66%, respectively. Release profile of sunitinib was different in three developed systems. Liposomes sustained drug release greater than that observed for the polymer nanospheres and solid lipid nanoparticles in the same period. SLN showed higher corneal retention of SUB when compared to other systems. Within thirty minutes corneal retention of SUB from SLN (15 µg/cm2) was more than twice that observed for liposomes (6.8 µg/cm2). NE also showed corneal retention of SUB (12.7 µg/cm2) superior to liposomes. Spectroscopic studies of electron paramagnetic resonance (EPR) comparing liposomes and SLN demonstrated that SLN are more flexible than liposomes. These studies also indicated that sub is located in the lipid bilayer of liposomes near the phospholipid-water interface, leading to increased rigidity. In SLN the drug is also probably located near the lipid-water interface, altering the crstaline organiation of the lipids and increased fluidity. These results justify the faster release profile observed for SUB from SLN and higher corneal retention of drug from these nanosystems. Employing alternative methods to the use of animals for determining the safety of the formulations, all three formulations developed showed no potential for ocular irritation in tests of bovine corneal opacity and permeability test method (BCOP), in the evaluation of hemolytic potential and in the test in chorioallantoic membrane of chicken egg (HET-CAM). Among the systems developed in this work containing SUB, SLN seems to present a greatest potential for clinical application in the treatment of VC.