Banca de DEFESA: ANDRE LEANDRO SILVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : ANDRE LEANDRO SILVA
DATA : 28/04/2017
HORA: 09:00
LOCAL: Faculdade de Farmácia
TÍTULO:

Study of amphotericin B molecular aggregation into different carrier systems

PALAVRAS-CHAVES:

A DEFINIR

PÁGINAS: 189
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

The amphotericin B (AmB) is a drug of peculiar physicochemical features: being amphiphilic and amphoteric. These characteristics turn difficult the drug load into therapeutic systems. AmB is currently available in the market as micelles, liposomes and lipid complex for injection. The literature show that there is an intimate correlation between the AmB bound to the carrier and its biological response. However, there is a deficiency concerning the physicochemical characterization of the available AmB-containing products. Therefore, the aim of this work was to characterize AmB-containing carriers seeking a prediction to its biological response. The AmB-containing micellar system was the first product available for clinical use. The patent of this product has already expired some years ago. In this work we have characterized the original system and two other similar micellar products. In addition, we studied the stability increase of heated systems, by the formation of AmB “super-aggregates”. AmBisome®, an AmB-containing liposomal system, was also characterized and, for the first time, tested for the possibility of super-aggregates formation. The AmB incorporation into nano and microemulsion systems was presented and the physicochemical characteristics evaluated, focusing mainly on applications for the treatment of fungal ocular diseases and also for visceral leishmaniasis. The main techniques used for characterization were electronic spectroscopy, circular dichroism and dynamic light scattering. The isothermal titration calorimetry (ITC) was used as an attempt to measuring the super-aggregates energy formation. Besides, an AmB soluble derivative was developed and characterized by atomic mass spectroscopy, infra-red, UV-Vis and circular dichroism. Then, this AmB-derivative was loaded into a microemulsion as a vehiculation strategy. The overall results show that the AmB-containing systems presented different molecular aggregation states that depends on the carrier, the way the drug is incorporated and also on the diluent. According to the literature, the aggregation state is associated with both, drug efficiency and toxicity. In nanoemulsion systems, the drug is found aggregated and multi-aggregated. In microemulsions, AmB is loaded as monomers. The heated micellar systems form AmB super-aggregates while the liposomal system is unable to form such molecular structure. Moreover, the AmB soluble derivative presented distinct features when compared to the original molecule. However, once incorporated into the microemulsion, the aggregation state is similar to that of the original AmB molecule, as supported by UV-Vis and circular dichroism results. It can be concluded that the AmB aggregation state varies according to the kind of carrier, the drug concentration and also the way of drug incorporation, even into one same carrier. Finally, the soluble derivative opens the possibility for drug carrying into aqueous vehicles for the treatment of many diseases by different administration routes.

MEMBROS DA BANCA:
Externo à Instituição - BOLIVAR PONCIANO GOULART DE LIMA DAMASCENO - UEPB
Presidente - 1178187 - ERYVALDO SOCRATES TABOSA DO EGITO
Externo à Instituição - FRANCELINE REYNAUD - UFRJ
Interno - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Externo ao Programa - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA