MARGARETH KAZUYO KOBAYASHI DIAS FRANCO

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  • Artigo IPEN-doc 29058
    Supramolecular structure organization and rheological properties modulate the performance of hyaluronic acid-loaded thermosensitive hydrogels as drug-delivery systems
    2023 - SEPULVEDA, ANDERSON F.; KUMPGDEE-VOLLRATH, MONT; FRANCO, MARGARETH K.K.D.; YOKAICHIYA, FABIANO; ARAUJO, DANIELE R. de
    The challenges for developing new pharmaceutical formulations based on natural and synthetic polymers has led to innovation into the design of systems responsive environmental stimuli such as temperature. However, the presence of hydrophilic or hydrophobic molecules, charged groups, or metallic elements can affect their structural behavior and their biopharmaceutical performance This work aims to study and characterize the morphology and structure of polymeric formulations based on Poloxamer (PL) 407 (15 % and 30 % m/v) and its binary with PL 338 (15 % PL 407 + 15 % PL 338) and hyaluronic acid (0.5 % m/v), as drug delivery systems of local anesthetic bupivacaine (0.5 % m/v) and ropivacaine (0.5 % m/v) hydrochloride. For this, it was performed SANS analysis for determination of supramolecular organization and lattice parameters; calorimetry was done to characterize their thermodynamic parameters; rheological analysis flow curve, consistency and adhesion calculation, Maxwell model study. Also, it was performed drug release profiles and calculation of diffusion coefficients. It was identified lamellar structures in PL 407 15 % formulations, and coexistence of cubic and hexagonal phases in PL 407 30 % and binary formulations, however hyaluronic acid, bupivacaine or ropivacaine seem do not affect the type of supramolecular structure. In addition, these additives can modulate viscosity among poloxamers chains, increasing micelle-micelle interactions as it happens in presence of bupivacaine. On the other hand, addition of hyaluronic acid can promote increased structural stabilization by hydrophilic interactions between hyaluronic and micellar corona. It reflects the ability how to control the drug release, as in case of binary system that retained bupivacaine for longer time than other systems, as well it happens when hyaluronic acid is added in PL 407 15 % and PL 407 30 %.
  • Artigo IPEN-doc 28130
    Sulforaphane-loaded hyaluronic acid-poloxamer hybrid hydrogel enhances cartilage protection in osteoarthritis models
    2021 - NASCIMENTO, MONICA H.M. do; AMBROSIO, FELIPE N.; FERRARAZ, DEBORA C.; WINDISCH-NETO, HERMANN; QUEROBINO, SAMYR M.; NASCIMENTO-SALES, MICHELLE; ALBERTO-SILVA, CARLOS; CHRISTOFFOLETE, MARCELO A.; FRANCO, MARGARETH K.K.D.; KENT, BEN; YOKAICHIYA, FABIANO; LOMBELLO, CHRISTIANE B.; ARAUJO, DANIELE R. de
    Sulforaphane (SFN) is an isothiocyanate with anti-arthritic and immuno-regulatory activities, supported by the downregulation of NF-κB pathway, reduction on metalloproteinases expression and prevention of cytokine-induced cartilage degeneration implicated in OA progression. SFN promising pharmacological effects associated to its possible use, by intra-articular route and directly in contact to the site of action, highlight SFN as promising candidate for the development of drug-delivery systems. The association of poloxamers (PL) and hyaluronic acid (HA) supports the development of osteotrophic and chondroprotective pharmaceutical formulations. This study aims to develop PL-HA hybrid hydrogels as delivery systems for SFN intra-articular release and evaluate their biocompatibility and efficacy for osteoarthritis treatment. All formulations showed viscoelastic behavior and cubic phase organization. SFN incorporation and drug loading showed a concentration-dependent behavior following HA addition. Drug release profiles were influenced by both diffusion and relaxation of polymeric chains mechanisms. The PL407-PL338-HA-SFN hydrogel did not evoke pronounced cytotoxic effects on either osteoblast or chondrosarcoma cell lines. In vitro/ex vivo pharmacological evaluation interfered with an elevated activation of NF-κB and COX-2, increased the type II collagen expression, and inhibited proteoglycan depletion. These results highlight the biocompatibility and the pharmacological efficacy of PL-HA hybrid hydrogels as delivery systems for SFN intra-articular release for OA treatment.
  • Artigo IPEN-doc 26393
    10000 years cement
    2019 - FERREIRA, EDUARDO G.A.; MARUMO, JULIO T.; FRANCO, MARGARETH K.K.D.; YOKAICHIYA, FABIANO; VICENTE, ROBERTO
    This review is focused on the long-term performance of cementitious materials in a repository for radioactive waste. During the last few years, the disposal of disused sealed radioactive sources (DSRS) in a borehole type repository has been studied by many countries. The borehole concept is particularly useful to dispose of spent nuclear fuel and DSRS. In boreholes for DSRS, cementitious materials are intended to be used as structural material, immobilization matrix and as backfill. The understanding of the performance of these materials is essential to ensure the safety of the facilities during their required lifetime, from centuries to many thousands of years, depending on the initial activity and half-life of the waste. This review approaches the behavior of the cement from the hydration and hardening to the long-term processes that can affect its durability. Three main causes of failure of repository-engineered barriers are recognized: a) the formation of a preferential pathway for the migration of the contained radionuclides to the biosphere; b) loss of resistance and cohesion of the structural cementitious material; and c) the increase in the corrosion processes of the metallic components of the structures that affect the overall containment of the facility.