Browsing by Author "Alves, Fernanda"

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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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    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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    Synergistic Tetracycline-Curcumin Association in Biocompatible PCL Nanostructured Wound Dressings
    (2024) Teodoro, Kelcilene Bruna Ricardo; Alvarenga, Augusto D.; Marques Chagas, Paulo Augusto; Lopes, Raphael Guimaraes; Alves, Fernanda; Stringasci, Mirian D.; Harb Buzza, Hilde; Inada, Natalia M.; Correa, Daniel Souza
    Open injuries, resulting from skin tissue ruptures, can expose the human body to pathogenic bacteria, presenting a significant risk for hospitalized patients and individuals with compromised immune systems. At the same time, developing alternative therapies usinginnovative methods of drug administration is crucial for combating antibacterial resistance. In this study, we present an approach for skin wound healing that synergistically combines a traditional antibiotic and an active natural compound in a polymer nanofibrous wound dressing. The fabrication strategy involved the solution blow spinning technique, which enabled easy, fast, and scalable manufacturing of polymer nanofibrous mats, while poly epsilon-caprolactone (PCL) was selected as the base polymer, due to its biocompatibility and nontoxicity for human tissues. The selected antibiotic formulation comprised a synergistic combination of tetracycline (TC) and curcumin (CC), aiming to incorporate reduced fractions of TC. Nanofibrous dressings measuring around 200 cm2 could be fabricated during 45 min. The results of physicochemical characterization showed that nanofibrous mats with fewer defects were obtained due to the presence of TC in the formulation, while the presence of CC improved the encapsulation efficiency and enabled a more controlled release of TC. The antimicrobial tests demonstrated that diminishing the quantity of TC in the nanofibrous mats had no discernible impact on their efficacy against Escherichia coli and Staphylococcus aureus. The results of in vitro cytotoxicity and in vivo tests showed that the proposed wound dressings were not cytotoxic (cell viabilities consistently exceeded 95% for human dermal fibroblasts) and did not lead to inflammation or damage in the healing process. Moreover, the study with real wounds on mice showed that the wound dressings containing the synergistic combination of TC and CC exhibited superior efficacy in promoting healing in comparison to the control group. Collectively, these findings demonstrate the potential of the developed nanostructured platfom for wound dressing applications.