Full text
| |
| Author(s): |
Jéssica Bernegossi
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Araraquara. 2018-07-31. |
| Institution: | Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara |
| Defense date: | 2018-01-31 |
| Advisor: | Marlus Chorilli; Lívia Nordi Dovigo |
| Abstract | |
Oral candidiasis is caused mainly by the opportunistic yeast Candida albicans. Treatment involves the administration of topical or systemic antifungal for which resistance has been observed. Researchers are looking for alternative methods, such as photodynamic therapy and the discovery of substances of natural origin that may be of therapeutic interest in the treatment of oral candidiasis, such as curcumin, whose antifungal action may be enhanced by the use of light, it also acts as a photosensitizer. However, this drug has limiting physical-chemical characteristics, such as low aqueous solubility. Therefore, its incorporation in liquid crystal precursor systems (LCPS) plus mucoadhesive polymers proves to be an interesting option to make its use feasible. The objective of this study is to evaluate the LCPS mucoadhesive for buccal administration of curcumin, as well as to verify the effect of oral candidosis treatment with the use of photodynamic therapy, using in vitro and in vivo studies. For this, LCPS compounds of oleic acid, ethoxylated and propoxylated cetyl alcohol (Procetyl® AWS) and polymer dispersion of poloxamer (16%) and/ or polyethyleneimine (0.5%), capable of incorporating curcumin, were developed. The compounds were characterized by using polarized light microscopy (PLM), rheology, scattering small angle X-ray scattering (SAXS) and mucoadhesion in vitro, before and after dilution with artificial saliva. In vitro release, permeation and retention ex vivo studies were carried out, as well as in vitro and in vivo biological assays for the evaluation of curcumin incorporated in LCPS versus Candida albicans. In PLM, it was possible to visualize the transition of LCPS, characterized as dark field, for hexagonal and lamellar mesophases, characteristics of liquid-crystalline systems. The rheological results evidenced that the systems obtained were initially Newtonian and after the addition of the artificial saliva were shown as non-Newtonian, pseudoplastic. SAXS results corroborated the results of PLM. In the in vitro mucoadhesion assay it was observed that there was greater force of attraction between the mucosa and the formulation in the samples that contained the union of the two polymers and after the addition of the artificial saliva. In the in vitro release assay it was observed that the systems modified the release profile of curcumin as compared to the drug in solution. In the ex vivo permeation assay it was observed that the systems were not able to permeate the esophageal membrane; however, significant amount of curcumin was detected in the retention assay. In the cell viability assay they showed that after 24 hours of the LCPS in contact with the tested cells, they still presented 75% of viable cells when compared to the control of living cells. The in vivo assay showed that after 24 hours of treatment there was no antimicrobial effect in relation to the positive control. However, data obtained in the animals analyzed after 7 days are promising, since complete killing was observed in some animals from the PP-CUR-PDT group. The histological images reveled presence of Candida albicans pseudo-hyphae in the epithelial tissue of the animals treated with PP-CUR in the absence of light irradiation. However, animals treated with the curcumin formulation in association with light did not present indicatives of yeast. Therefore, the results obtained in this work suggest that the developed and characterized systems presented characteristics desired in the treatment of oral candidosis, in order to facilitate the application and permanence in the mucosa of the mouth, being also able to control the release of curcumin. (AU) | |
| FAPESP's process: | 14/22045-9 - Mucoadhesive precursor systems of liquids crystals for buccal administration of curcumin associated with photodynamic therapy in the treatment of oral candidiasis |
| Grantee: | Jéssica Bernegossi |
| Support Opportunities: | Scholarships in Brazil - Doctorate |