Dissertação
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança
Fecha
2023-07-05Autor
Felix, Igor Roesch
Institución
Resumen
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.