Banca de DEFESA: JOSÉ ROBÉRIO DE OLIVEIRA NETTO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : JOSÉ ROBÉRIO DE OLIVEIRA NETTO
DATE: 30/12/2024
TIME: 08:00
LOCAL: Google Meet
TITLE:

Nanoformulations based on Copaifera reticulata Ducke and trans-dehydrocrotonin: physicochemical characterizations and evaluation of antioxidant and cytotoxic effects

KEY WORDS:

Copaifera reticulata Ducke; trans-dehydrocrotonin; SNEDDS systems; Physicochemical characterizations; Antioxidant and citotoxic analysis.

PAGES: 101
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Among the herbal resources of Brazilian biodiversity, stand out the natural products copaiba oil extracted from species of the genus Copaifera and the bioactive 19-nor-clerodane trans-dehydrocrotonin (t-DCTN), obtained from Croton cajucara Benth. The main objective of this research was to develop a colloidal SNEDDS formulation based on Copaifera reticulata Ducke copaiba resin oil (OCPR), as a carrier system of the bioactive t-DCTN. Chromatographic analyses were performed for C. reticulata (GC-MS) and the hydroalcoholic extract from stem bark of C. cajucara, for isolation of t-DCTN. The chemical structure of t-DCTN was analyzed by spectroscopic methods (IR and 1H NMR). The SNEDDS-OCPR system, free of co-surfactants containing copaiba oil (C. reticulata) and Tween 80, was prepared using a ternary phase diagram based on the determination of the maximum solubility of the active matter (surfactant) in the aqueous and oily phases, by means of mass titrations. The diterpene t-DCTN (1 mg) solubilized drop by drop with SNEDDS-OCPR by mechanical stirring under heating (40 oC to 55 oC), formed the nanoproduct SNEDDS-OCPR-DCTN (1 mg/mL). The formulations were evaluated in in vitro experimental models for antioxidant [reducing activity equivalent to ascorbic acid (CAT), reducing power, chelating activity of copper ions and hydroxyl radical scavenging, as well cytotoxic by the MTT method [bromide of (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium], using macrophages and murine fibroblasts of the L-929 lineage. The encapsulation efficacy of t-DCTN was evaluated by the minimum and maximum solubility method, and quantification was performed by UV-visible (λmax 238 nm). Transmission electron microscopy (TEM) analysis of the SNEDDS-CO carrier showed the presence of spherical nanoparticles with an average size between 80 nm and 70 nm. The particle size, PDI and Zeta potential analyses showed, respectively, mean values of 11.66 nm, 0.17 and -3.85 for SNEDDS-OCPR, and 11.29 nm, 0.10 and -3.44 mV for SNEDDS-OCPR-DCTN, indicating that there was a small and uniform distribution of the nanodroplets in both systems. The in vitro kinetic profiles of encapsulated t-DCTN (SNEDDS-OCPR-DCTN) were evaluated using the dialysis technique, providing t-DCTN release profiles according to the Fickian model, in which t-DCTN reached a maximum cumulative sustained release of 90.33 ± 0.01% (360 min.). The antioxidant effect of both SNEDDS-OCPR and SNEDDS-OCPR-DCTN systems showed potential antioxidant results. Comparatively, SNEDDS-OCPR-DCTN showed strong CAT activity, as well as reducing power and sequestration of superior hydroxyl radicals. The SNEDDS-OCPR system showed better activity in the chelating activity assay. In the cell viability tests, the findings showed that SNEDDS-OCPR-DCTN at concentrations 100 μg/mL and 200 μg/mL inhibited 99% of fibroblasts. At concentrations below 25 μg/mL, fibroblast viability exceeded 70%. In contrast, the system demonstrated a distinct behavior in relation to macrophages, maintaining cell viability above 50% at the highest concentrations. For the L-929 lineage, an IC50 of 35.54 μg/mL was observed. Under specific conditions, the drug delivery systems SNEDDS-OCPR and SNEDDS-OCPR-DCTN formed fine nanoemulsions with significant efficacy for the bioavailability of copaiba oil co-encapsulated with t-DCTN, being considered potential antioxidants. In this sense, the new nanobioproducts are bioavailable for future in vivo pharmacological investigations.

COMMITTEE MEMBERS:
Presidente - ***.201.654-** - MARIA APARECIDA MEDEIROS MACIEL - UnP
Externo ao Programa - 2941160 - JOSE HERIBERTO OLIVEIRA DO NASCIMENTO - UFRNExterna ao Programa - 1754360 - WALDENICE DE ALENCAR MORAIS LIMA - UFRNExterna à Instituição - AUREA ECHEVARRIA AZNAR NEVES LIMA - UFRRJ
Externa à Instituição - Nereide Stela Santos Magalhães - UFPE