MARGARETH KAZUYO KOBAYASHI DIAS FRANCO
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Artigo IPEN-doc 30845 Influence of structural organization on mucoadhesive properties of poloxamer-hyaluronic acid-based micelles and hydrogels2024 - 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. deNew 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.Artigo IPEN-doc 28684 Monoketonic curcuminoid-lidocaine co-deliver using thermosensitive organogels2022 - 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. deOrganogels (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.Artigo IPEN-doc 27384 Capsaicin-cyclodextrin complex enhances mepivacaine targeting and improves local anesthesia in inflamed tissues2020 - 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 deAcidic 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.Artigo IPEN-doc 24763 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-release2018 - NASCIMENTO, M.H.M.; FRANCO, M.K.K.D.; YOKAICHYIA, F.; PAULA, E. de; LOMBELLO, C.B.; ARAUJO, D.R. deIn 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.