MARGARETH KAZUYO KOBAYASHI DIAS FRANCO

MARGARETH KAZUYO KOBAYASHI DIAS FRANCO

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Influence of structural organization on mucoadhesive properties of poloxamer-hyaluronic acid-based micelles and hydrogels
2024 - SEPULVEDA, ANDERSON F.; SILVA, JESSICA B. da; BRUSCHI, MARCOS L.; FRANCO, MARGARETH K.K.D.; YOKAICHIYA, FABIANO; TOFOLI, GIOVANA R.; CEREDA, CINTIA M.S.; ROSSO, ANABELLA P.; GIACOMELLI, FERNANDO C.; SCOTT, ANA L.; ARAUJO, DANIELE R. de
New pharmaceutical formulations have been proposed as strategies to improve transport and provide best conditions to control the drug release rate in specific biological environments, such as mucosa surfaces. Herein, formulations containing binary systems Poloxamer (PL) 407 15 % and PL 338 15 %, combined with hyaluronic acid, carrying the local anesthetic bupivacaine (BVC), were studied by molecular dynamics, while other structural parameters were determined by Dynamic Light Scattering for stablishing relationships with mucoadhesive properties and cytotoxicity evaluation. The binary system PL 407 15 %/PL 338 15 % exhibited a well-organized structural morphology, with more hydrated corona, and increased mucoadhesive properties over mucin layers. After hyaluronic acid (HA) incorporation, it was observed an increase on the force of detachment, possibly due to HA role as a linker among mucin layers independently of PL supramolecular structures. On the other hand, the addition of BVC or HA/BVC into the binary system decreased the force of detachment, as a response of augmented of compactness of these hydrogels caused by desolvation of PO core, showing the influence of all components and their chemical interactions into the structural organization and their biopharmaceutical performance relationships.
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 %.
Monoketonic curcuminoid-lidocaine co-deliver using thermosensitive organogels
2022 - VIGATO, ARYANE A.; MACHADO, IAN P.; VALLE, MATHEUS del; ANA, PATRICIA A. da; SEPULVEDA, ANDERSON F.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K.K.D.; LOIOLA, MESSIAS C.; TOFOLI, GIOVANA R.; CEREDA, CINTIA M.S.; SAIRRE, MIRELA I. de; ARAUJO, DANIELE R. de
Organogels (ORGs) are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug-carrier systems, considering the application of synthetic monoketonic curcuminoid (m-CUR) and lidocaine (LDC) to treat topical inflammatory lesions. The monoketone curcuminoid (m-CUR) was synthesized by using an innovative method via a NbCl5–acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate (IPM), soy lecithin (LEC), and the synthesized m-CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico-chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m-CUR shifted the sol-gel transition temperature, and that the addition of LDC enhanced the rheological G′/G″ ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy (FTIR), where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography (OCT) analysis revealed that LEC and m-CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin-delivery.
POLYana
2021 - SEPULVEDA, ANDERSON F.; FRANCO, MARGARETH; YOKAICHIYA, FABIANO; ARAUJO, DANIELE de
INTRODUCTION POLYAna is a new executable software developed by SISLIBIO group for rheological analysis of hydrogel and organogel systems and other colloidal materials (nanoparticles and micelles). The software development aims to facilitate the analysis of rheology data associated to both temperature- and frequency-dependent analysis, viscosity and curve flow profiles. OBJECTIVES The software development aims to facilitate the analysis of rheology data associated to both temperature- and frequency-dependent analysis, viscosity and curve flow profiles. MATERIALS AND METHODS From raw data, several models are applied like power-law model for frequency response and curve flow, Boltzmann law to calculate gelation temperature and viscosity response under temperature,Maxwell model to study interchain relationships in addition to other models such as Bingham model, Cross model, and Herschel-Bulkley are also available. POLYana outputs calculates rheological parameters like consistency, adhesion, hysteresis, flow index, G’/G” ratio. DISCUSSION AND RESULTS To validate results obtained from POLYana, same data were analyzed by applying other programs and same mathematical models. In this sense, rheological analysis of Poloxamer 407 in water solution (15 %) were performed: from temperature-dependent G’ and G” analysis were obtained gelation temperature of 45.46 ± 0.02 °C, η_0 = 0.08 ± 0.03 mPa*s, η_max = (32.44 ± 0.17) mPa*s and dη/dT = (1.27 ± 0.02) mPa*s/°C by fitting Boltzmann law (R2 = 0.998), which are similar to results obtained by others softwares and found in literature. From temperature-dependent G’ and G” analysis, it gets adhesion value of (1647.15 ± 18.01) mPa*sn calculated from power-law model (R2 = 0.869), also similar to PRISM results. CONCLUSION Also, other Poloxamer concentrations and hydrogels types have been evaluated, showing close numbers to that previously reported. In order to stablish structural relationships, one of POLYana tools is also to analyze small-angle neutron scattering (SANS) and develop Monte Carlo simulation for SANS and rheological analysis, simultaneously.
POLYana
2021 - SEPULVEDA, ANDERSON F.; FRANCO, MARGARETH; YOKAICHIYA, FABIANO; ARAUJO, DANIELE de
POLYAna is a new executable software developed by SISLIBIO group for rheological analysis of hydrogel and organogel systems and other colloidal materials (nanoparticles and micelles). The software development aims to facilitate the analysis of rheology data associated to both temperature- and frequency-dependent analysis, viscosity and curve flow profiles. The software development aims to facilitate the analysis of rheology data associated to both temperature- and frequency-dependent analysis, viscosity and curve flow profiles. From raw data, several models are applied like power-law model for frequency response and curve flow, Boltzmann law to calculate gelation temperature and viscosity response under temperature, Maxwell model to study interchain relationships in addition to other models such as Bingham model, Cross model, and Herschel-Bulkley are also available. POLYana outputs calculates rheological parameters like consistency, adhesion, hysteresis, flow index, G’/G’’ ratio. To validate results obtained from POLYana, same data were analyzed by applying other programs and same mathematical models. In this sense, rheological analysis of Poloxamer 407 in water solution (15 %) were performed: from temperature-dependent G’ and G’’ analysis were obtained gelation temperature of 45.46 ± 0.02 °C, η_0 = 0.08 ± 0.03 mPa*s, η_max = (32.44 ± 0.17) mPa*s and dη/dT = (1.27 ± 0.02) mPa*s/°C by fitting Boltzmann law (R2 = 0.998), which are similar to results obtained by others softwares and found in literature. From temperature-dependent G’ and G’’ analysis, it gets adhesion value of (1647.15 ± 18.01) mPa*sn calculated from power-law model (R2 = 0.869), also similar to PRISM results. Also, other Poloxamer concentrations and hydrogels types have been evaluated, showing close numbers to that previously reported. In order to stablish structural relationships, one of POLYana tools is also to analyze small-angle neutron scattering (SANS) and develop Monte Carlo simulation for SANS and rheological analysis, simultaneously.
Supramolecular structure of temperature-dependent polymeric hydrogels modulated by drug incorporation
2020 - FRANCO, MARGARETH K.K.D.; SEPULVEDA, ANDERSON F.; VIGATO, ARYANE A.; OSHIRO, ALISSON; MACHADO, IAN P.; KENT, BEN; CLEMENS, DANIEL; YOKAICHIYA, FABIANO; ARAUJO, DANIELE R. de
Poloxamers or Pluronics® (PL) have been described as promising pharmaceutical and cosmetics matrices. Herein, we have explored the structural organization of hydrogel formulations composed of PL F‐127 and PL L‐81, considering their different hydrophilic‐lipophilic balances and interactions with an antimigraine drug, sumatriptan succinate (SMT). Hydrogels phase organizations were investigated by X‐ray diffraction (XRD) and Small Angle Neutron Scattering (SANS) to establish the relationship between structural features and drug release modulation. XRD analysis revealed very low intensity peaks for hydrogels containing SMT due to the presence of small amounts of SMT as crystalline form, which is an evidence of drug incorporation into hydrogels. At physiological temperature, a structural transition from lamellar to hexagonal was observed after SMT incorporation. In addition, SANS patterns displayed a distorted hexagonal structure, (calculated q2 >experimental q2), indicating the presence of a comprised structure compared to a perfect hexagonal assembly. This structural shift however have no influence on the drug release mechanism, allowing the SMT molecules to access the micellar and intermicellar hydrophilic spaces, with release mechanism dependent on the drug diffusion (R2=0.998 ≥ 0.986) from the hydrogel to the medium and release constant (Krel) values from 9.8 to 14.7 %.h−1; 31.5 to 39.1 %.h−1/2; 0.84 to 1.2 %.h−n for Zero‐order, Higuchi and Korsmeyer‐Peppas models, respectively. Using SMT as a drug model, it could be concluded that the drug access to the micellar/intermicellar hydrophilic spaces can be modulated by interplaying the polarity of binary PL‐based hydrogels. Therefore, drug release constants and mechanisms will be then dependent on the hydrogels physico‐chemical and structural properties, which determine the drug diffusion from the hydrogel to the release medium.
Capsaicin-cyclodextrin complex enhances mepivacaine targeting and improves local anesthesia in inflamed tissues
2020 - COUTO, VERONICA M.; OLIVEIRA-NASCIMENTO, LAURA de; CABEÇA, LUIZ F.; GERALDES, DANILO C.; COSTA, JULIANA S.R.; RISKE, KARIN A.; FRANZ-MONTAN, MICHELLE; YOKAYCHIYA, FABIANO; FRANCO, MARGARETH K.K.D.; PAULA, ENEIDA de
Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-β-CD), as shown by the phase solubility study. The resulting complex (HP-β-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and 1H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.
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.
Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release
2018 - NASCIMENTO, M.H.M.; FRANCO, M.K.K.D.; YOKAICHYIA, F.; PAULA, E. de; LOMBELLO, C.B.; ARAUJO, D.R. de
In this study,we reported the hyaluronic acid (HA) on supramolecular structure of Pluronic F-127 (PLF-127) and/ or Pluronic F-108 (PLF-127) hydrogels, as well as their effects on release mechanisms, looking forward their application as lidocaine (LDC) drug-delivery systems in arthroplastic surgeries.We have studied the HA-micelle interaction using Dynamic Light Scattering (DLS), themicellization and sol-gel transition processes by Differential Scanning Calorimetry (DSC) and Rheology., of PL-based hydrogels and. The presence of HA provided the formation of larger micellar dimensions from ~26.0 to 42.4 nm. The incorporation of HA did not change the micellization temperatures and stabilized hydrogels rheological properties (G′ N G″), showing no interference on PLthermoreversible properties. Small-Angle-X-ray Scattering (SAXS) patterns revealed that HA incorporation effects were pronounced for PLF-127 and PLF-108 systems, showing transitions from lamellar to hexagonal phase organization (HA-PLF-127) and structural changes from cubic to gyroid and/or cubic to lamellar. The HA insertion effects were also observed on drug release profiles, since lower LDC release constants (Krel = 0.24–0.41 mM·h−1) were observed for HA-PLF-127, that presented a hexagonal phase organization. Furthermore, the HA-PL systems presented reduced in vitro cytotoxic effects, pointed out their tendency to selfassembly and possible application as drug delivery systems.