JUSTINE PAULA RAMOS DE OLIVEIRA

JUSTINE PAULA RAMOS DE OLIVEIRA

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Fabrication of green nanomaterials
2023 - THIPE, VELAPHI C.; FREITAS, LUCAS F.; LIMA, CAROLINE S.A.; BATISTA, JORGE G.S.; FERREIRA, ARYEL H.; OLIVEIRA, JUSTINE P.R. de; BALOGH, TATIANA S.; KADLUBOWSKI, SLAWOMIR; LUGAO, ADEMAR B.; KATTI, KATTESH V.
The purpose of this chapter is to discuss the production of biocompatible green nanomaterials for biomedical applications using green nanotechnology. To enhance drug loading and delivery, these nanomaterials are engineered with immunomodulatory ligands such as phytochemicals (Epigallocatechin gallate, Mangiferin, Resveratrol), proteins (albumin and papain), crosslinked hydrogels, and nanogels. The nanomaterials described herein are synthesized via redox potential of electron-dense phytochemicals that reduce metallic precursors to their stable corresponding nanoparticles and via water radiolysis with ionizing radiation as a green approach (due to the absence of any reducing agent) for use as radiosensitizers (albumin and papain nanoparticles) in nuclear medicine – theranostics applications. The phytochemicals facilitate the delivery of nanoparticles through receptor mediated endocytosis, while the proteins such as papain, due to their proteolytic action enhances the permeation of nanoparticles into tumor tissue, and albumin increase the pharmacokinetic efficiency of these nanoparticles. The nanoparticles developed have shown effectiveness against a variety of human cancers while posing no toxicity to normal tissue. Additionally, a pilot human clinical combing Ayurvedic medicine with green nanomedicine is given as a novel approach for treating breast cancer and other related illnesses. Finally, the importance of ecotoxicology for nanomaterials is discussed in order to provide safety data in relevant multiple species (fish, daphnia, algae, rodents, etc.) with paratope/epitope distributions for evaluating tissue cross-reactivity profiles in human tissues and to provide critical information on in vivo toxicity in order to predict the possible adverse effects of nanomaterials on human and environmental health as an effort to establish regulatory limits and ISO standards for nanomaterials.
Solubility study of Kraft lignin for the development of electrospun nanofibers
2022 - NOGUEIRA, K.M.; VARCA, J.O.; LIMA, C.S.; CRUZ, C.C. da; RIBEIRO, A.H.; FREITAS, L.F.; VARCA, G.H.; LUGAO, A.B.
Lignin is a high-volume byproduct of paper manufacturing which has been explored in many research fields, especially for the development of fiber and nanofiber for biomedical applications [1,2]. This work presents a solubility study performed through gravimetry for kraft lignin considering its application for the development of electrospun nanofibers [3]. In practical terms, lignin was solubilized in alkaline aqueous solution, dimethylformamide and dimethylsulfoxide, at concentrations of 10, 15 and 20% (w/v) and varying temperatures of 25, 50 and 75 ºC, under constant stirring. After solubilizing, the solution was filtered, and the insoluble fraction was dried in the oven at 100 ºC. At 25 ºC lignin was insoluble in all solvents tested, as predicted using Hansen solubility parameters. Although the increase in temperature promoted lignin solubilization in all solvents tested, at the highest temperature assayed, the solubilization was facilitated, presenting the smallest levels of the insoluble fraction. Lignin was soluble in all solvents tested, and optimum solubility conditions were achieved using 10% lignin solutions (w/v), without significant insoluble fraction, and therefore ideal concentration for the development of lignin based fibers.
A biological study of gelatin-PVA based scaffold functionalized with albumin for biomedical purposes
2022 - VARCA, J.O.; KLINGBEIL, F.; NOGUEIRA, K.M.; LIMA, C.S.; CRUZ, C.C. da; FREITAS, L.F.; VARCA, G.H.; MATHOR, M.B.; LUGAO, A.B.
Biomaterials have been designed for tissue reconstruction, bone regeneration and cell culture, and functionalized with presence of proteins, nanoparticles, peptides and other components to improve the biocompatibility for instance. This work shows a biological study of gelatin-PVA based scaffold with controlled pore size and functionalized with albumin for biomedical purposes. The in vitro study comprises cytotoxicity, cell adhesion and proliferation assessment. In practical terms, the gelatin-PVA scaffold crosslinked and sterilized by gamma radiation followed by freeze-drying was evaluated by cytotoxicity, adhesion and proliferation tests. The cytotoxicity results showed that the biomaterial produced was non-toxic, and adhesion and proliferation assays showed that the material was suitable for tissue engineering. The presence of albumin did not present a significant impact on the cell performance, at the assayed concentration.
Mucoadhesive polymers and their applications in drug delivery systems for the treatment of bladder cancer
2022 - LIMA, CAROLINE S.A. de; VARCA, JUSTINE P.R.O.; ALVES, VICTORIA M.; NOGUEIRA, KAMILA M.; CRUZ, CASSIA P.C.; RIAL-HERMIDA, M. ISABEL; KADLUBOWSKI, SLAWOMIR S.; VARCA, GUSTAVO H.C.; LUGAO, ADEMAR B.
Bladder cancer (BC) is the tenth most common type of cancer worldwide, affecting up to four times more men than women. Depending on the stage of the tumor, different therapy protocols are applied. Non-muscle-invasive cancer englobes around 70% of the cases and is usually treated using the transurethral resection of bladder tumor (TURBIT) followed by the instillation of chemotherapy or immunotherapy. However, due to bladder anatomy and physiology, current intravesical therapies present limitations concerning permeation and time of residence. Furthermore, they require several frequent catheter insertions with a reduced interval between doses, which is highly demotivating for the patient. This scenario has encouraged several pieces of research focusing on the development of drug delivery systems (DDS) to improve drug time residence, permeation capacity, and target release. In this review, the current situation of BC is described concerning the disease and available treatments, followed by a report on the main DDS developed in the past few years, focusing on those based on mucoadhesive polymers as a strategy. A brief review of methods to evaluate mucoadhesion properties is also presented; lastly, different polymers suitable for this application are discussed.
Development of Lignin/PEO nanofibers by electrospinning technique for tissue engineering application
2020 - NOGUEIRA, K.M.; VARCA, J.O.; LIMA, C.S.; CRUZ, C.C. da; RIBEIRO, A.H.; FREITAS, L.F.; VARCA, G.H.; LUGAO, A.B.
Lignin is a renewable carbon source and has been widely explored in different areas over the last years, especially in biomaterials such as dressings and other biomedical devices due its natural origin and low cost. Its chemical structure confers interesting properties such as antioxidant capacity, UV protection, bactericidal action and appropriate adsorption. Poly (ethylene oxide) (PEO) is used in electrospinning to facilitate the formation polymer fibers. The electrospinning technique has been largely explored in the bioengineering area towards designing nanomaterial with minimum defect and high surface area. The present work aimed the development of a lignin/PEO nanofiber by electrospinning technique. In practical terms, lignin/PEO solution was prepared following two different methods. In the first approach, polymer stock solutions were prepared in alkaline water by stirring at 70 °C. In the second, the polymer powders were mixed and dissolved together in dimethylformamide (DMF) under stirring at 80 °C. By both methods, PEO/lignin solutions were prepared at 10, 20 e 30% (w,v) solid content, at the ratios 99/1 and 95/5. For electrospinning parameters, the distance between ejector and plate collector was set to 15-20 cm, voltage to 20 kV and injection flow to 1 mL/h, chamber temperature to 40 °C and 30%. Nanofiber morphology was assessed by scanning electron microscopy and optical coherence tomography. Apparent porosity was measured by classical Archimedes method. Due to higher DMF dielectric constant compared to water, results showed that nanofibers made using DMF presented smaller beats formation and smaller fiber diameter. Nanofibers with higher solid content presented more uniform fibers with larger diameter. Nanofibers with higher lignin concentration presented larger number of beats and higher fiber diameter. However, lignin improved the system porosity in all cases. Further mechanical and biological experiments will be done, nevertheless, the nanofiber developed is a promising material to be applied in tissue engineering.
CMC and PVA hydrogel containing papain nanoparticles for drug delivery
2020 - LIMA, C.S.; VARCA, G.H.; OLIVEIRA, J.R.; NOGUEIRA, K.M.; SANTOS, F.A.; RIBEIRO, A.H.; LUGAO, A.B.; FREITAS, L.F.; ROGERO, S.O.
Four hydrogel formulations of Carboxymethylcellulose (CMC) and Poly (vinyl alcohol) (PVA) were prepared with native papain (AP and BP) and papain nanoparticles (AN and BN) for drug delivery. The formulations were evaluated for their preliminary stability, protein distribution in the matrix and cytotoxicity. Three methods for sterilization purposes were compared: irradiation by 60Co source, electron-beam and UV light. The preliminary stability test confirmed that the system was stable since there was no precipitation or alteration of the organoleptic properties of the samples in the evaluated period. The distribution of proteins in the hydrogel was very homogeneous in all the formulations. Quantification of the enzymatic activity of papain after contact with the gel showed that native papain maintained its activity high (86% and 93% for AP and BP gels, respectively), whereas there was a considerable drop in the activity of the papain nanoparticles to 60.54% and 69.44% for AP and BP gels, respectively. Such loss of activity is attributed to processing and/or process steps. The cell viability assay showed that the polymer matrix shows no cytotoxicity, corroborating with the literature, since the material is biocompatible. Thus, it is possible to affirm that the developed system presents potential for biomedical application, either as a vehicle of papain itself or for the transport of other drugs through complexation with papain nanoparticles. However, the need for further studies of stability, controlled release capacity and biocompatibility is required.
Semi-solid pharmaceutical formulations for the delivery of papain nanoparticles
2020 - LIMA, CAROLINE S.A. de; VARCA, JUSTINE P.R.O.; NOGUEIRA, KAMILA M.; FAZOLIN, GABRIELA N.; FREITAS, LUCAS F. de; SOUZA, ELISEU W. de; LUGAO, ADEMAR B.; VARCA, GUSTAVO H.C.
Papain is a therapeutic enzyme with restricted applications due to associated allergenic reactions. Papain nanoparticles have shown to be safe for biomedical use, although a method for proper drug loading and release remains to be developed. Thus, the objective of this work was to develop and assess the stability of papain nanoparticles in a prototype semi-solid formulation suitable for dermatological or topical administrations. Papain nanoparticles of 7.0 ± 0.1 nm were synthesized and loaded into carboxymethylcellulose- and poly(vinyl alcohol)-based gels. The formulations were then assayed for preliminary stability, enzyme activity, cytotoxicity studies, and characterized according to their microstructures and protein distribution. The formulations were suitable for papain nanoparticle loading and provided a stable environment for the nanoparticles. The enzyme distribution along the gel matrix was homogeneous for all the formulations, and the proteolytic activity was preserved after the gel preparation. Both gels presented a slow release of the papain nanoparticles for four days. Cell viability assays revealed no potential cytotoxicity, and the presence of the nanoparticles did not alter the microstructure of the gel. The developed systems presented a potential for biomedical applications, either as drug delivery systems for papain nanoparticles and/or its complexes.
An updated review of macro, micro, and nanostructured hydrogels for biomedical and pharmaceutical applications
2020 - LIMA, CAROLINE S.A. de; BALOGH, TATIANA S.; VARCA, JUSTINE P.R.O.; VARCA, GUSTAVO H.C.; LUGAO, ADEMAR B.; CAMACHO-CRUZ, LUIS A.; BUCIO, EMILIO; KADLUBOWSKI, SLAWOMIR S.
Hydrogels are materials with wide applications in several fields, including the biomedical and pharmaceutical industries. Their properties such as the capacity of absorbing great amounts of aqueous solutions without losing shape and mechanical properties, as well as loading drugs of different nature, including hydrophobic ones and biomolecules, give an idea of their versatility and promising demand. As they have been explored in a great number of studies for years, many routes of synthesis have been developed, especially for chemical/permanent hydrogels. In the same way, stimuli-responsive hydrogels, also known as intelligent materials, have been explored too, enhancing the regulation of properties such as targeting and drug release. By controlling the particle size, hydrogel on the micro- and nanoscale have been studied likewise and have increased, even more, the possibilities for applications of the so-called XXI century materials. In this paper, we aimed to produce an overview of the recent studies concerning methods of synthesis, biomedical, and pharmaceutical applications of macro-, micro, and nanogels.
The effects gamma radiation dose on the swelling capacity of PVP/lignin hydrogels dressings for wound treatment
2019 - NOGUEIRA, K.M.; VARCA, J.O.; LIMA, C.S.A.; VARCA, G.; LUGAO, A.B.; FREITAS, L.F.
Lignin is a carbon renewable source and has been widely explored in different areas in the last years, especially in the biomaterials field as dressings and other biomedical devices due its natural origin and low cost (1). Its chemical structure confers important properties to this macromolecule such as antioxidant capacity, UV protection and bactericidal activity (2,3). Polivinylpirrolidone (PVP) is a polymer widely applied for biomedical applications due to its relevant properties, such as the water absorption capacity, suitable mechanical properties for wound healing applications, and the capacity to originate hydrogels with different characteristics (4). Gamma radiation is a relevant option to produce biomedical devices, as the technology allows polymer crosslinking and sterilization in a single step (5). Two polymer solutions were prepared, PVP 10% (w, v) in distiled water (neutral pH) with poly(ethylene glycol) diacrylate (1.0% w/v) and lignin 6% (w, v) (pH > 13) and homogenized separately, until complete dissolution. The solutions were mixed in the follow ratios 95/5, 90/10 and 80/20, in which were added to a 2% (w, v) of agar and mixed at 70 ºC for 30 minutes. Samples were disposed in glass moulds and irradiated at 25, 50 and 100 kGy at dose rate of 5 kGy/h in a 60Co irradiator. Samples assessed by autoclave presented higher swelling than the PVP control, but lower gel fraction in comparison with the standard, except for formulation 90:10. Swelling and Gel Fraction were also evaluated by shaker at 37 ºC for 24 h. The results showed that the increase of dose decrease the swelling capacity and gel fraction decrease with the increase of lignin in the formulations. In general, the hydrogels irradiated at 25 and 50 kGy, except for formulation 80:20 at 25 kGy, presented good integrity and suitable results to be considered for the next steps of the study and are promising for biomedical application.
Natural polymer hydrogels with gold nanoparticles for bladder cancer chemotherapy delivery
2019 - LIMA, C.S.A.; VARCA, G.; DE FREITAS, L.F.; VARCA, J.O.; LUGAO, A.B.
The treatment of bladder cancer is done by transurethral resection for tumor removal, followed by immune or chemotherapy intravesical, according to the stage of the disease. The main objective of this work was to develop and characterize strategies to increase the residence time and specificity of chemotherapy through the application of hydrogels for chemotherapy and /or immunotherapy administration. Natural polymers gellan gum and microcrystalline cellulose were chosen to prepare the hydrogels as they are already widely used in the biomedical area due to characteristics such as the absence of toxicity, high biocompatibility, and biodegradability. Papain-coated gold nanoparticles were added to the gels to promote chemo or immunotherapeutic permeation. Preliminary stability assays were carried out to evaluate the compatibility between the polymeric matrices and the gold nanoparticles. The systems were characterized by Scanning Electron Microscopy, and Fourier Transform Infrared Spectroscopy. The results allowed the identification of the polymer groups present in the formulations, as well as the evaluation of the interactions between the hydrogel network and the nanoparticles. The formulations were suitable for the proposed application.