JUSTINE PAULA RAMOS DE OLIVEIRA
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Artigo IPEN-doc 29052 Mucoadhesive polymers and their applications in drug delivery systems for the treatment of bladder cancer2022 - 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.Resumo IPEN-doc 25541 Development of gelatin based scaffold by gamma radiation for application as platelet rich plasma support for wound treatment2018 - VARCA, JUSTINE P.R.O.; FERRARI, ANDRE; PIGNATA, DANILO R.; GUAZZELLI, STEFANE K.; KLINGBEIL, MARIA F.G.; VARCA, GUSTAVO H.C.; LUGAO, ADEMAR B.; MATHOR, MONICA B.Gelatin is a natural polymer originated from the collagen, and presents poor mechanical properties, however it is a natural and biocompatible polymer, and collagen is the main component of the extracellular matrix1. Poly-vynil (alcohol) is an artificial polymer with interesting mechanical properties and biocompatibility. Such polymers have been largely scientific studied for biomedical application2. Platelet Rich Plasma (PRP) has been widely scientific explored in many medical fields in the last decades, especially in orthopedic area and in athletic treatments3. Based on the PRP desired properties regarded to the tissue regeneration, the present work aimed to develop a scaffold to support PRP release for wound treatment and study the influence of different radiation doses on a scaffold formation to apply as support for PRP release for wound treatment. In specific terms, the impact of radiation will be evaluated through physicochemical and morphologic characteristics. In the study, two polymers of different characteristics were applied, and scaffolds were prepared based on two formulations, one composed by gelatin (7%, w/w) and PVA (5%, w/w), and the second by gelatin (10%, w/w) and PVA (5%, w/w). The formulations were solubilized together in distilled water and heated up to 80 ºC under constant stirring for 1 hour. Posteriorly, the blends were disposed in circular glass molds. The samples were cooled at 4 ºC for at least 24 h and then irradiated at 15, 25 and 50 kGy. After irradiation, the samples were frozen and freeze dried. The scaffolds were characterized in terms of structure and morphology by mechanical assays, differential scanning calorimetry, scanning electron microscopy, optical coherence tomography and infrared spectroscopy. In addition, platelet adhesion and release, and cytotoxic assays were also performed. Samples irradiated at 15 kGy presented pore size diameter of around 1.4 μm and porosity of 54%, while samples irradiated at 25 kGy, presented pore size diameter of around 1.1 μm and porosity of 49%. Optical coherence tomography showed that gelatin control samples presented more superficial degradation as irradiation dose increased, while PVA control sample presented higher integrity, indicating that this polymer is less sensitive to gamma radiation. The system presented suitable mechanical properties and the platelet adhesion and release assays showed that the scaffold presented adequate pore size range to host and release the platelets, and non-cytotoxic to platelets, featuring adequate properties to be applied as dressing for wound treatments.Resumo IPEN-doc 25414 Development of mucoadhesive PVA/CMC based hydrogel for intravesical chemotherapy2018 - LIMA, C.S.A.; VARCA, J.O.; FERRARI, A.; NOGUEIRA, K.M.; VARCA, G.H.C.; LUGAO, A.B.Bladder cancer (BC) is one of the main diseases that attack the urinary tract and is globally responsible for 165,000 deaths per year. Bladder tumor may be classified as non-muscle invasive (superficial) or muscle invasive. About 70% of patients present the superficial bladder cancer which is treated by transurethral resection for tumor removal followed by intravesical chemo or immunotherapy. The main challenge reported in the instillation of chemotherapy is the limited drug residence time in the bladder as a consequence of urine levels that leads to fast drug removal from the bladder.1 Hydrogels are chemically or physically crosslinked polymer systems that form three-dimensional networks with high water absorption capacity. Carboxymethylcellulose (CMC) is one of the major soluble derivatives of cellulose widely applied in the medical and pharmaceutical fields due to its biocompatibility, nontoxicity, biodegradability and film forming ability.2 Polyvinyl Alcohol (PVA) is a synthetic polymer with wide pharmaceutical and biomedical applications as it is nontoxic, non-carcinogenic, bioadhesive and easy to process.3 In this work, we developed a mucoadhesive hydrogel from a CMC and PVA polymer blend for chemotherapeutic loading and suitable rheological properties for intravesical instillation, especially designed for treating superficial BC with increased residence time of chemotherapeutic agent. Three formulations (C1, C2 and C3) at different CMC concentrations were prepared - 1%, 2% and 3% (w/v), respectively. PVA concentration corresponded to 1% (w/v) for all formulations. The polymers were separately solubilized in Milli-Q water and then mixed prior to the addition of 20% (v/v) glycerin to increase the mucoadhesiveness of the material. The hydrogels were characterized according to their organoleptic and rheological properties to evaluate the behavior of the material under tension and temperature. Accelerated stability tests of the pharmaceutical form were also performed. Comparatively, formulations with glycerin presented improved mucoadhesiveness, and formulations with 1 and 2% of CMC presented more adequate rheological behavior for the proposed application. In conclusions, the systems presented adequate properties for the delivery of chemotherapeutic agents for optimized BC treatments.Resumo IPEN-doc 25412 Development of lignin-PVP based dressing for wound treatment2018 - NOGUEIRA, K.M.; VARCA, J.O.; VARCA, G.H.C.; LIMA, C.S.A.; LUGAO, A.B.Lignin is a carbon renewable source and has been widely explored in different fields in the last years, especially in biomaterials as dressing and other biomedical devices due its natural origin and low cost1. Poly(ethylene oxide) (PEO) is a synthetic polymer largely used in biomedical applications due its important characteristics such as high hydrophilicity, non-toxicity and ease of process2. The present work aimed to develop a lignin-PEO based dressing for wound treatment by casting. In specific terms, three different polymer blends were formulated using a range of 3 to 10% (w/v) lignin was tested with the addition of 1 to 3% PEO. Lignin was solubilized in aqueous solution (pH>13) alkalized with sodium hydroxide and PEO was solubilized in distilled water. The solutions were heated up to 70 ºC and homogenized until complete polymer dissolution. Then, PEO solution and poly(ethylene glycol) diacrylate (PEGDA) (0.5 - 1.0%) were added to the lignin solution and the blend was mixed for 30 minutes at 70 ºC. Posteriorly the blends were submitted to casting and drying under different conditions, room temperature for 48 hours and incubated at 40 ºC for 24 hours. A control sample of 6% lignin was prepared in the same conditions. Samples were evaluated by physico-chemical and morphological characterizations. The swelling and gel fraction profiles were assessed as well as thermal behavior by differential scanning calorimetry. Chemical modifications were evaluated by infrared spectroscopy. Samples with higher PEGDA content presented minor swelling index. The blends formulated presented different thermal behavior in comparison with the control. Infrared spectroscopy pointed some chemical modifications promoted by the crosslinking agent. In general terms, the material developed presented a potential to continue been explored as dressing for wound treatment