doctoralThesis
Desenvolvimento de sistemas terapêuticos para leishmaniose cutânea
Fecha
2019-09-26Registro en:
ALEXANDRINO JÚNIOR, Francisco. Desenvolvimento de sistemas terapêuticos para leishmaniose cutânea. 2019. 85f. Tese (Doutorado em Nanotecnologia Farmacêutica) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2019.
Autor
Alexandrino Júnior, Francisco
Resumen
This study aimed to develop therapeutic alternatives containing
amphotericin B (AmB) for the treatment of cutaneous leishmaniasis. Therefore,
polymeric systems with distinct geometry (films and fibers) and hydrophilicity
(polyvinyl alcohol) and poly(lactic acid)) were produced, and their respective
kinetic release profiles were evaluated and correlated with these production
parameters and thermodynamic parameters. The data indicated that the drug
release was an endothermic and non-spontaneous process, with the fibers and
films appropriately fitting to Peppas – Sahlin and Higuchi’s model, respectively.
Among the systems evaluated, PVA hydrogels performed the best controlled
release and, therefore, their properties as a potential therapeutic system was
further evaluated in vitro. The results highlighted that the system was able to
control the water vapor permeation, at levels compatible with the skin in its
physiological state, acted as a physical barrier against microorganisms present
in the environment, and simultaneously displayed efficient antifungal and antileishmania activity, without potential cytotoxicity to renal cells (VERO cell line).
Meanwhile, microemulsions (ME) containing 14 %w/w of poloxamer 407 were
developed, which provided to the system a thermoreversible behavior (gelation
in situ at ~ 25 °C), facilitating its topical application. The poloxamer 407
attenuated the instability phenomena in the ME system during the storage
period at 2 °C, without affecting the half-life of the drug. Regarding the ex vivo
dermal retention of AmB, it was possible to infer that ME acted as a
permeabilizing agent, enabling after 24h of exposition, an AmB dermal retention
of ~ 1,37 ± 0,75 g/cm2
. However, the presence of polymer in the system
reduced the diffusion rate of AmB, in such a way that no drug was detected
during the in vitro assay. Although there is a required in vivo endorsement, the
results obtained here demonstrate that PVA hydrogels and thermo-responsive
ME are promising systems for use in combination therapy, allowing for
outpatient topical treatment of cutaneous leishmaniasis.