Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança

• Ano de defesa: 2023
• Autor(a) principal: Felix, Igor Roesch
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Farmácia; UFSM; Programa de Pós-Graduação em Ciências Farmacêuticas; Centro de Ciências da Saúde
• Palavras-chave em Português: Eudragit® RL100; Nanopartículas; Fotoestabilidade; Compostos fenólicos; Mucosite; Nanoparticles; Photodegradation; Phenolic compounds; Mucositis; CNPQ::CIENCIAS DA SAUDE::FARMACIA
• Link de acesso: http://repositorio.ufsm.br/handle/1/30074

Oral mucositis is characterized by the appearance of erythematous and ulcerative lesions in the oral cavity induced by chemotherapies and radiotherapies, that damage on basal layer of the tissues lead to the expression of pro-inflammatory, pro-apoptotic cytokines and reactive oxygen species (ROS) capable of compromising cellular DNA and triggering other processes of cell apoptosis in the other layers of the epithelium. At low levels, oxidative stress induced by ROS can be prevented through the action of antioxidants. In this context, phenolic compounds have stood out for their property of reducing inflammatory response and potent antioxidant action through the reduction of RSOs. The oral administration of active pharmaceutical ingredients is an alternative in the treatment of oral lesions, being more effective when associated to mucoadhesive formulations. In this sense, polymeric nanoparticles arise, colloidal systems capable of promoting adhesiveness between the body mucosa and its polymers, increasing the retention time of the formulations in the therapeutic target and, consequently, the bioavailability of the compounds. The present work aimed to develop suspensions of cationic nanospheres containing caffeic acid (CA) and ferulic acid (FA) associated, with adequate physicochemical characteristics and potential for incorporation into final pharmaceutical forms. To do this, the antioxidant activity of the suspensions was evaluated by ABTS and DPPH. The photostability of the systems was analyzed, identifying the degradation products formed, as well as assays of mucoadhesion, irritative potential (HET-CAM) and cell viability (murine 3T3 fibroblasts). In addition to developing and validating an analytical methodology for quantification by CLAE. The nanospheres were obtained by the nanoprecipitation method. For physicochemical characterization the following parameters were analyzed: macroscopic analysis, pH values, average particle diameter and polydispersity (photon correlation spectroscopy), zeta potential (electrophoretic mobility). The determination of the content of the compounds and encapsulation efficiency by CLAE method and morphological analysis by atomic force microscopy. The in-vitro release was performed by the diffusion method in dialysis bags and the photostability test was performed with exposure to UVA radiation (365 nm). During the execution of this work, a promising suspension of nanospheres with homogeneous particle size, encapsulation efficiency (>60%), morphology, positive zeta potential and suitable pH was obtained. The nanoparticles showed bioadhesive capacity in the mucoadhesion assay, besides maintaining antioxidant activity and decreasing the irritation potential of the compounds. In the photodegradation assay, it was possible to observe a protective effect of the nanospheres on the phenolic compounds. This work evaluated, in an unprecedented character, the trans-cis isomerization of CA and FA promoted by exposure to UV radiation. The analytical methodology validated for quantification of phenolic compounds proved to be able to quantify both CA and FA simultaneously. In view of the above, nanoformulations containing coencapsulated phenolic acids show promise for future therapeutic application and incorporation into pharmaceutical forms for oral use.