Banca de DEFESA: DOUGLAS DOURADO OLIVEIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : DOUGLAS DOURADO OLIVEIRA
DATE: 28/07/2022
TIME: 09:00
LOCAL: REMOTO
TITLE:

MICROEMULSION-BASED ORGANOGEL NANOPARTICLES: A PROMISSING APPROACH FOR CURCUMIN DELIVERY

KEY WORDS:

Organogel; low molecular weight gelator; curcuminoids; nanotechnology; oral administration.

PAGES: 150
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUBÁREA: Farmacotecnia
SUMMARY:

Curcumin is a polyphenol obtained from the rhizome of Curcuma longa, which has stood out due to its high biological potential. However, this molecule is a Class IV compound in the biopharmaceutical classification (low water solubility and low permeability), which compromises its bioavailability in a physiological environment. Additionally, this molecule is not only susceptible to intense metabolism, being rapidly eliminated, but also presents worrisome instability in the gastrointestinal pH. To circumvent limitations of class IV molecules, the use of lipid nanoparticles (NPs) has been suggested. Among these, organogel nanoparticles may be highlighted. These are reservoir systems that shows nanometric hydrophobic particles with gel characteristics. Altogether, these features allow greater stability and higher entrapment of drugs when compared to conventional lipid NPs. Due to their recent development, these NPs require improvements (size decrease and uniformity of NPs) to achieve increased permeability and bioavailability when administered orally. In this perspective, the aim of this thesis was to develop curcumin-entrapped organogel nanoparticles using microemulsions (10-100 nm) as a template system for particle size reduction and uniformity. Studies were initially developed to evaluate the solubility of curcumin in surfactants, oil and different proportions of surfactants: oil mixtures. Then, a pseudoternary phase diagram was developed by the water titration method to obtain microemulsion (ME) regions. The systems were emulsified by an ultrasound probe. An oil-in-water (O/W) formulation with low concentration of surfactants and an oil phase adequate for entrapment curcumin was selected. A ME with curcumin was produced by adding the drug to the mixture of compounds before emulsification. The MEs were characterized in terms of droplet size distribution, electrical conductivity, surface tension, rheology, morphology and thermal profile. The entrapment efficiency (EE) was determined by high performance liquid chromatography. Additionally, the stability over time of MEs and stability in simulated gastrointestinal fluid (SGIF) was assessed. Finally, the kinetics of curcumin release in SGIF was also evaluated. Posteriorly, different concentrations of low molecular weight gelators were added to the oil phase of the ME and mixed by high and low energy methods. The obtained dispersions were initially characterized by turbidimetry and hydrodynamic particle size distribution. Subsequently, the chosen samples were further characterized in terms of zeta potential, morphology, surface tension and rheology. In addition, the stability over time and in SGIF was assessed. The obtained NPs were loaded with curcumin (Curc-ME-Org-NPs). They were characterized in terms of physicochemical stability (storage and in FGIS), morphology, rheology, % EE and release kinetics. Finally, Curc-ME-Org-NPs displayed spherical shape (with the presence of a surfactant corona) with an average hydrodynamic size of 22 nm, monomodal distribution, negative surface charge, Newtonian profile and low surface tension, characteristics similar to the template ME. Curc-ME-Org-NPs showed high entrapment efficiency, physicochemical stability over time and in SGIF. Furthermore, it revealed modified release kinetics that fitted models that describe a complex release mechanism, but with the presence of diffusion. Therefore, Curc-ME-Org-NPs proved to be a potential formulation for oral administration with stability and in vitro oral bioavailability.

COMMITTEE MEMBERS:
Presidente - 1178187 - ERYVALDO SOCRATES TABOSA DO EGITO
Externo ao Programa - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR - UFRNExterna à Instituição - ELIANA MARTINS LIMA - UFG
Externo à Instituição - FRANCISCO HUMBERTO XAVIER JUNIOR - UFPB
Externa à Instituição - RENATA FONSECA VIANNA LOPEZ - USP
Externo à Instituição - ÉVERTON DO NASCIMENTO ALENCAR - UFG