Banca de QUALIFICAÇÃO: ANDRE LEANDRO SILVA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : ANDRE LEANDRO SILVA
DATA : 07/02/2017
HORA: 09:00
LOCAL: Sala do Consec, CCS – UFRN
TÍTULO:

A DEFINIR

PALAVRAS-CHAVES:

A DEFINIR

PÁGINAS: 161
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

The amphotericin B (AmB) is a drug of peculiar physico-chemical features: being amphiphilic and amphoteric. These characteristics turn difficult the drug load into theurapeutic systems. AmB is currently available in the market as micelles, liposomes and lipidid complex for injection. The literature show that there is an intimate relation between the AmB bound to the carrier and its biological response. However, there is a deficiency concerning the physicochemical characterization of available AmB-containing products. Therefore, the aim of this work was to charachterize AmB-containing carriers seeking a prediction to its biological response. The AmB-containing micellar systems were the first products available to the clinics. Then, the patent for this product has already expired since some years ago. In this work we have characterized the original system and other two micellar similar 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 had the possibility of super-aggregates formation tested, as occurs for micellar systems. The AmB incorporation into nano and microemulsion systems was presented and the physico-chemical characteristics studied with applications to fungal ocular diseases and also to visceral leishmaniasis treatment. 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 of measuring the super-aggregates energy formation. Besides of that, an AmB soluble derivative was developed and characterized by atomic mass spectroscopy, infra-red, UV-Vis and circular dichroism. Then, the derivative was loaded into a microemulsion as a vehiculation strategy. The overall results show that the AmB-containing systems present different molecular aggregation states which depends on the carrier, the incorporation way and also on the diluents used for system redisperstion. From the literature, the aggregation state is associated with both, drug efficacy and toxicity. Into nanoemulsion systems, the drug is aggregated and multi-aggregated. Into the microemulsion, AmB is loaded as monomers. The heated micellar systems form AmB super-aggregates, the liposomal system is unable to form this molecular structure. The AmB soluble derivative presented distinct features when compared to the original molecule. However, after microemulsion loading, the aggregation state changed, being similar to that of the original AmB as supported by UV-Vis and circular dichroism. It can be concluded that the AmB aggregation state varies not only according to the kind of carrier but also with the drug concentration and 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 ao Programa - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Externo à Instituição - FRANCELINE REYNAUD - UFRJ
Interno - 373.201.654-49 - MARIA APARECIDA MEDEIROS MACIEL - UNP