doctoralThesis
Delineamento de biocompósitos baseados em paligorsquita e quitosana como carreadores de etambutol
Fecha
2019-03-29Registro en:
MEIRELLES, Lyghia Maria Araújo. Delineamento de biocompósitos baseados em paligorsquita e quitosana como carreadores de etambutol. 2019. 168f. Tese (Doutorado em Desenvolvimento e Inovação Tecnológica em Medicamentos) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2019.
Autor
Meirelles, Lyghia Maria Araújo
Resumen
Tuberculosis, a transmissible disease that affects the lungs for infection by Mycobacterium
tuberculosis, is still a serious public health problem, ranking ninth in the global cause of
death, with millions of new cases each year. One problem associated with the treatment of
tuberculosis refers to the requirement of administration of four drugs (ethambutol, rifampicin,
isoniazid, and pyrazinamide) as a fixed dose combination product, which leads to interaction
and stability problems. Considering the difficulty found in this treatment, this work proposed
to develop composites to carry the tuberculostatic ethambutol based on palygorskite, a
fibrous clay mineral, with a high specific area and moderately negative charge, and on the
cationic biopolymer chitosan. In this sense it was intended to improve the stability of the
formulation, using raw materials widely available in the Northeast region of Brazil. Initially
composition and purity of chitosan and palygorskite were determined and the adsorption
study of the drug to the phyllosilicate was carried out. Molecular modeling was performed in
order to predict the possibility of interaction and to determine the potential sites involved in
the adsorption of the drug to the phyllosilicate. Then, the product of this interaction (ETB /
Paly) was characterized using spectroscopic (FTIR, XRD, EDS) and thermoanalytical (DSC
and TG) techniques, microscopy, hygroscopicity, stability and in vitro release assays. The
interaction between palygorskite and chitosan was performed by the solution intercalation
method, obtaining a composite that was characterized by the evaluation of the surface
charge, specific area, thermal analysis, FTIR and XRD. The biocomposites loaded with
ethambutol were obtained by the spray drying technique and the main physicochemical
properties of the microparticles were determined as well as their biocompatibility. In silico
analysis indicated that drug adsorption to the clay mineral occurred spontaneously, the main
groups involved were palygorskite Si-OH and ethambutol -OH and -NH2 groups. The results
obtained corroborate with the computational analysis, demonstrating a high adsorption
capacity of the tuberculostatic onto the inorganic carrier, predominantly on the surface,
homogeneously distributed and promoting a reduction of drug hygroscopicity in the hybrid
form (ETB / Paly), in relation to the free drug. Analysis of the biocomposites based on
chitosan-palygorskite evidenced the involvement of electrostatic and hydrogen interactions
between the raw materials, with superficial adsorption of the polymer to the phyllosilicate. In
addition, the composites loaded with ethambutol presented as spherical microparticles,
biocompatible and with a controlled release profile, influenced by the polymer: phyllosilicate
rate. Therefore, the results obtained indicated the effectiveness of the system in modulating
the pH-dependent release of ethambutol, reinforcing the involvement of electrostatic
interactions between the components. Also, the use of biocompatible materials led to
composites with reduced cytotoxicity in the 3T3 cell line, mainly in the systems based on
palygorskite. This dataset allows us to envisage the possibility of applying these
biocomposites in the treatment of tuberculosis as a simple and low-cost alternative for
technological difficulties related to the current therapeutic regimen.