Browsing by Author "Buzza, Hilde Harb"

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    Fast Fabrication of Multifunctional PCL/Curcumin Nanofibrous Membranes for Wound Dressings
    (2023) Teodoro, Kelcilene Bruna Ricardo; Alvarenga, Augusto Duarte; Rocha Oliveira, Luis Fernando; Marques Chagas, Paulo Augusto; Lopes, Raphael Guimaraes; Andre, Rafaela da Silveira; Mercante, Luiza Amim; Alves, Fernanda; Stringasci, Mirian Denise; Buzza, Hilde Harb; Inada, Natalia Mayumi; Correa, Daniel Souza
    Therapeutic intervention to skin wounds requires coveringthe affectedarea with wound dressings. Interdisciplinary efforts have focusedon the development of smart bandages that can perform multiple functions.In this direction, here, we designed a low cost (U$0.012 per cm(2)) multifunctional therapeutic wound dressing fabricated byloading curcumin (CC) into poly(epsilon-caprolactone) (PCL) nanofibersusing solution blow spinning (SBS). The freestanding PCL/CC bandageswere characterized by distinct physicochemical approaches and weresuccessful in performing varied functions, including controlled releaseof CC, colorimetric indication of the wound conditions, barrier againstmicroorganisms, being biocompatible, and providing a photosensitiveplatform for antimicrobial photodynamic therapy (aPDT). The chemicalnature of PCL and CC and the interactions between these componentsallowed CC to be released for 192 h (ca. 8 days), which could be correlatedwith the Korsmeyer-Peppas model, with a burst release suitableto treat the inflammatory phase. Due to the CC keto-enol tautomerism,an optical indication of the healing status could be obtained usingPCL/CC, which occurred immediately, ranging between red/orange andyellow shades. The effect against pathogenic microorganisms evaluatedby agar disc-diffusion, affected skin wound simulation (ex vivo),and microbial penetration tests demonstrated the ability to blockand inhibit microbial permeation in different environments. The biocompatibilitiesof PCL and PCL/CC were verified by in vitro cytotoxicity study, whichdemonstrated that cell viabilities average above 94 and 96% for humandermal fibroblasts. In addition, the proposed bandage responded toaPDT applied to an in vivo assay, showing that, when irritated, PCL/CCwas able to reduce the bacteria present on the real wound of mice.In summary, our findings demonstrate that using PCL and CC to producenonwovens by the SBS technique offers potential for the rapid fabricationof biocompatible and multifunctional wound dressings, paving the wayfor large-scale production and utilization of such dressings in thetreatment of skin wounds.
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    Photodynamic inactivation strategies for maximizing antifungal effect against Sporothrix spp. and Candida albicans in an in vitro investigation
    (2024) Rocha, Amanda Regina; Inada, Natalia Mayumi; da Silva, Ana Paula; Bagnato, Vanderlei Salvador; Buzza, Hilde Harb
    Background Sporotrichosis is a zoonotic disease caused by the dimorphic fungus Sporothrix spp., leading to skin lesions that can, in some cases, progress and result in the death of infected individuals. Candida albicans is another fungus involved in several skin, oral, and vaginal mucosal infections. Fungal diseases are concerning due to increasing incidence and the limited variety of antifungal classes available for treatment. Furthermore, antifungal medications can cause various side effects, exacerbated by their prolonged use during infection treatment. There is a need to explore alternatives to conventional drugs that are effective, fast, and safe in combating sporotrichosis. This study aimed to achieve in vitro elimination of the fungi Sporothrix brasiliensis and Sporothrix schenckii through Photodynamic Inactivation (PDI), using curcumin as a photosensitizer and in combination with antifungal agents used in the treatment of sporotrichosis.Methodology Yeasts of Candida albicans, Sporothrix brasiliensis, and Sporothrix schenckii were subjected to Photodynamic Inactivation (PDI) using light at a wavelength of 450 +/- 10 nm, irradiance of 35 mW/cm2, delivering a fluence of 31.5 J/cm2, with curcumin as the photosensitizer at doses ranging from 0.75 to 150 mu g/mL. After determining the Minimum Inhibitory Concentration (MIC) values of the antifungal drugs itraconazole, ketoconazole, and potassium iodide, sub-MIC doses of these antifungals were combined with sub-MIC doses of curcumin in a new PDI session.Conclusion Photodynamic inactivation is a promising technique in the treatment of sporotrichosis, as well as its combination with antifungals. The combination of curcumin in concentrations ranging from 0.75 g/mL a 7.5 g/mL with sub-MIC concentrations of itraconazole, ketoconazole, and potassium iodide was able to completely inactivate the fungi C. albicans, S. brasiliensis and S. schenckii, indicating that PDI may increase the effectiveness of antifungals. However, further studies are needed to establish protocols for future clinical applications.
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    Porphyrin nanoemulsion for antimicrobial photodynamic therapy: effective delivery to inactivate biofilm-related infections
    (2022) Buzza, Hilde Harb; Alves, Fernanda; Tome, Ana Julia Barbosa; Chen, Juan; Kassab, Giulia; Bu, Jiachuan; Bagnato, Vanderlei Salvador; Zheng, Gang; Kurachi, Cristina
    The management of biofilm-related infections is a challenge in healthcare, and antimicrobial photodynamic therapy (aPDT) is a powerful tool that has demonstrated a broad-spectrum activity. Nanotechnology has been used to increase the aPDT effectiveness by improving the photosensitizer's delivery properties. NewPS is a simple, versatile, and safe surfactant-free nanoemulsion with a porphyrin salt shell encapsulating a food-grade oil core with promising photodynamic action. This study evaluated the use of NewPS for aPDT against microorganisms in planktonic, biofilm, and in vivo models of infected wounds. First, the potential of NewPS-mediated aPDT to inactivate Streptococcus pneumoniae and Staphylococcus aureus suspensions was evaluated. Then, a series of protocols were assessed against S. aureus biofilms by means of cell viability and confocal microscopy. Finally, the best biofilm protocol was used for the treatment of S. aureus in a murine-infected wound model. A high NewPS-bacteria cell interaction was achieved since 0.5 nM and 30 J/cm(2) was able to kill S. pneumoniae suspension. In the S. aureus biofilm, enhanced efficacy of NewPS-aPDT was achieved when 100 mu M of NewPS was applied with longer periods of incubation at the light dose of 60 J/cm(2). The best single and double-session protocol reduced 5.56 logs and 6.03 logs, respectively, homogeneous NewPS distribution, resulting in a high number of dead cells after aPDT. The in vivo model showed that one aPDT session enabled a reduction of 6 logs and faster tissue healing than the other groups. In conclusion, NewPS-aPDT may be considered a safe and effective anti-biofilm antimicrobial photosensitizer.
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    Potential of curcumin-loaded cubosomes for topical treatment of cervical cancer
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022) Victorelli, Francesca Damiani; Manni, Livia Salvati; Biffi, Stefania; Bortot, Barbara; Buzza, Hilde Harb; Lutz-Bueno, Viviane; Handschin, Stephan; Calixto, Giovana; Murgia, Sergio; Chorilli, Marlus; Mezzenga, Raffaele
    Cervical cancer is one of the most common cancers affecting women worldwide. There are an estimated 570.000 new cases of cervical cancer each year and conventional treatments can cause severe side effects. In this work, we developed a platform for vaginal administration of lipophilic drugs for cervical cancer treatment. We formulated mucoadhesive cubosomes for the delivery of curcumin, a lipophilic drug for cervical cancer treatment, to increase its bioavailability and local absorption. This study tests the use of cubosomes for vaginal drug administration and assesses their potential efficiency using the CAM (chick embryo chorioallantoic membrane) model. SAXS (small-angle X-ray scattering), cryo-TEM (cryotransmission electron microscopy), and dynamic light scattering (DLS) were employed to characterise the system. With ex vivo permeation and retention studies, we find that the curcumin released from our system is retained in the vaginal mucosa. In vitro cytotoxicity assay and cellular uptake showed an increased cytotoxic effect of curcumin against HeLa cell line when incorporated into the cubosomes. The curcumin-loaded cubosomes also demonstrated an antiangiogenic effect evaluated in vivo by the CAM model. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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    Ultrasonic scalpel associated with photodynamic therapy in the treatment of refractory vulvar condyloma acuminatum
    (2024) dos Santos, Valter Fausto; de Barros, Ian Carlos; de Arruda, Semira Silva; Buzza, Hilde Harb; Inada, Natalia Mayumi; Bagnato, Vanderlei Salvador; Stringasci, Mirian Denise
    This is a case report of a patient with vulvar condyloma acuminatum associated with hyperkeratosis and folliculitis, which had been refractory to two previous therapies. The patient had been successfully treated using a combination of promising techniques: the ultrasonic scalpel and MAL photodynamic therapy.