Banca de DEFESA: FRANCISCO ALEXANDRINO JÚNIOR

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : FRANCISCO ALEXANDRINO JÚNIOR
DATE: 16/12/2019
TIME: 18:00
LOCAL: Auditorio 2 do evento ISM
TITLE:

Development of therapeutic systems for cutaneous leishmaniasis

KEY WORDS:

Amphotericin B; leishmaniasis; microemulsion; skin; stability  

PAGES: 122
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

This thesis is part of the group's efforts to develop therapeutic alternatives containing amphotericin B (AmB) for the treatment of leishmaniasis. Since the instability of AmB, when present in an aqueous medium, is a complex mechanism, dependent on factors such as the state of aggregation, degree of ionization (pKa) and pH of the medium, the first chapter aimed to determine the pKa values of AmB in distinct hydroalcoholic solutions through Bjerrum plot. Such an approach provided support to elaborate a mathematical model with suitable predictive and explanatory capacity. Therefore, allowing a better understanding of the mechanisms involved in the aqueous instability of AmB. The second chapter aimed to evaluate the kinetic profiles of AmB released from polymeric systems with different geometry (fibers and films) and composition (polyvinyl alcohol (PVA) and poly(lactic acid) (PLA)) and to correlate such profiles with thermodynamic parameters. The results suggest that the drug release was an endothermic and non-spontaneous process, with kinetic profiles of fibers and films consistent to the Peppas-Sahlin and Higuchi model, respectively. Since the PVA hydrogels demonstrated a better control in the AmB release, its properties as a potential therapeutic system were evaluated in vitro in the third chapter. Wherein the results revealed that the system was able to control the water vapor permeation to levels compatible with the skin in its physiological state. Additionally, it displayed effective antifungal and antileishmanial activity, without potential cytotoxicity for VERO cells. The fourth chapter reports the results obtained in the development and evaluation of AmB-loaded thermo-responsive microemulsions (ME). In which the ME enabled the AmB skin retention, and the instability phenomena of ME caused by thermodestabilization were hindered by adding poloxamer 407 into the system. Thus, the results obtained herein demonstrate that PVA hydrogels and thermo-responsive ME are potential systems to be used in the topical outpatient treatment of cutaneous leishmaniasis.

BANKING MEMBERS:
Externo à Instituição - HELVECIO VINICIUS ANTUNES ROCHA - Fiocruz - RJ
Externo à Instituição - ADRIANA RAFFIN POHLMANN - UFRGS
Externa à Instituição - ELIANA MARTINS LIMA - UFG
Presidente - 1178187 - ERYVALDO SOCRATES TABOSA DO EGITO
Externo à Instituição - FREDERIC JEAN GEORGES FREZARD - UFMG