Desenvolvimento, caracterização e avaliação da eficácia de sistemas nanoestruturados contendo tacrolimus em modelo experimental da doença do olho seco.

• Ano de defesa: 2024
• Autor(a) principal: Janine Braga de Souza
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; FARMACIA - FACULDADE DE FARMACIA; Programa de Pós-Graduação em Ciências Farmacêuticas; UFMG
• Palavras-chave em Português: Nanopartículas catiônicas; Nanopartículas aniônicas; Ácido hialurônico; Sistema coloidal híbrido; Doença do olho seco; Modelo animal; Mucoadesão; Estudos de biocompatibilidade ocular
• Link de acesso: http://hdl.handle.net/1843/73465

Dry eye disease (DED) is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Several studies have demonstrated the potential use of the immunomodulator tacrolimus (TAC) in dry eye treatment. Due to the low ocular bioavailability of drugs administered by eye drops and the high prevalence of DED disease, the development of new safe options to increase precorneal time and/or drug penetration is justified. Thus, the goal of this project was to investigate the efficacy of nanostructured polymeric systems containing TAC with opposite superficial surfaces for the topical ocular treatment of DED. The manufacturing process of the NTAC nanoparticle was by interfacial deposition of preformed polymer method. The polymer used was Eudragit® RL100.The coated (anionic) nanoparticles with hyaluronic acid (NTAC-HA) were prepared by the surface adsorption technique from preformed NTAC. Various physical characterization tests were performed. For NTAC, the particle size was 166.7±0.29 nm, the polydispersibility index was 0,061 ± 0.01, zeta potential was +63.73 ±9.58 mV and pH= 4.68 ± 0.09. The NTAC-HA results were: 227.2 ± 1.30 nm; 0.44 ± 0.01; -30.03 ± 0.55 mV and 6.17 ± 0.01 respectively. The drastic inversion in the nanoparticle surface charge showed that the coating process was successfully and efficiently performed. The encapsulation efficiency of NTAC was 91.02% ± 0.71.The nanoformulations were classified as nanocapsules by morphological analysis. The interaction between the polymers used to prepare the nanostructured systems and the mucin suspension (1%) showed their mucoadhesive properties. The ocular irritation study was performed using the Hen's egg chorioallantoic membrane test (HET-CAM) and the Draize test (in vivo), and both nanoformulations were classified as non-irritating. The in vivo DED model was chemically induced using atropine sulfate. Topical application of NTAC and NTAC-HA, after DED diagnostic confirmation, once a day for seven days, restored tear volume back to baseline, film stability and repaired damaged epithelial cells. Therefore, these findings clearly illustrate the potential of these nanoparticles for DED treatment.