A esporotricose, uma doença fúngica causada pelo Sporothrix e afetando tanto humanos quanto felin... more A esporotricose, uma doença fúngica causada pelo Sporothrix e afetando tanto humanos quanto felinos, é comumente tratada com Itraconazol oral por períodos prolongados, porém a crescente resistência ao antifúngico decorrente de interrupções no tratamento tem sido observada. Diante desse cenário, os óleos essenciais e extratos de plantas surgem como potenciais alternativas terapêuticas mais eficazes em comparação aos fármacos existentes. O objetivo desta revisão é oferecer uma visão abrangente e atualizada sobre óleos e extratos vegetais contra cepas de Sporothrix spp., que possam contribuir futuramente para o desenvolvimento de terapias mais eficazes e seguras para essa importante zoonose. Os estudos in vitro avaliaram a ação fungistática pela determinação da Concentração Inibitória Mínima (CIM) e a ação fungicida pela determinação da Concentração Fungicida Mínima (CFM), este ultimo incluindo estudos de viabilidade celular. Os estudos in vivo em modelo animal, no geral determinaram a redução dos sintomas da doença e carga fúngica, remissão dos sintomas clínicos e disseminação do fungo para órgãos. Os estudos analisados indicaram que esses compostos vegetais têm potencial eficácia contra o fungo, especialmente para as cepas de S. brasiliensis e S. schenckii, entretanto é necessário uma padronização metodológica para comparação adequada dos resultados. Em geral, a utilização futura destes antifúngicos naturais em formulações orais ou tópicas pode representar um avanço significativo no tratamento da esporotricose felina, minimizando suas complicações.
Journal of Pharmacy and Pharmacology, Mar 29, 2018
Objectives The aim of this article was to use copaiba oil (C.O) to improve skin permeability and ... more Objectives The aim of this article was to use copaiba oil (C.O) to improve skin permeability and topical anti-inflammatory activity of celecoxib (Cxb). Methods Formulations containing C.O (1-50%) were associated with Cxb (2%). In vitro skin permeability studies were conducted using porcine ear skin. Histological analysis of the hairless mice skin samples after application of formulations was achieved with the routine haematoxylin/eosin technique. The anti-inflammatory activity was assessed using the AA-induced ear oedema mice model. Key findings The formulation containing 25% C.O promoted the highest levels of in vitro Cxb permeation through pig ear skin, retention in the stratum corneum (SC) and epidermis/dermis of pig ear skin in vitro (~5-fold) and hairless mice skin in vivo (~2.0-fold), as compared with the control formulation. At 25%, C.O caused SC disorganization and increased cell infiltration and induced angiogenesis without clear signs of skin irritation. The formulation added to 25% C.O as adjuvant inhibited ear oedema and protein extravasation by 77.51 and 89.7%, respectively, and that it was, respectively, 2.0-and 3.4-fold more efficient than the commercial diethylammonium diclofenac cream gel to suppress these inflammatory parameters. Conclusions 25% C.O is a potential penetration enhancer for lipophilic drugs like Cxb that can improve cutaneous drug penetration and its anti-inflammatory activity.
. "For me my research represents much more than three lines in my CV. It raised questions which I... more . "For me my research represents much more than three lines in my CV. It raised questions which I answered. It was a test which I passed. A battle which I won. It was an experience ingrained with long days and nights, and many tears of frustation. It was a work ethic and way of thinking that will be me forever. descongelamento (LUVETs) seguido por extrusão 3.2.2.2. Obtenção dos lipossomos por técnica de fase reversa (REVs) 3.2.3. Avaliação dos lipossomos obtidos 3.2.3.1. Caracterização dos lipossomos vazios (LUVETs e REVs) por cromatografia de exclusão em gel. 3.2.3.2. Caracterização dos lipossomos contendo 5-ALA (REVs) por cromatografia de exclusão em gel a) Determinação do perfil de eluição do 5-ALA em solução b) Determinação do perfil de eluição dos lipossomos com 5-ALA e) Determinação do volume de etanol para a solubilização das vesículas lipossômicas 3.2.3.3. Microscopia de luz polarizada 3.2.3.4. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 3.2.4. Calorimetria Exploratória Diferencial (DSC) 3.2.4.1. Obtenção dos filmes lipídicos para análise de DSC 3.2.5. Estudos in vitro de permeação e retenção cutâneas 50 50 51 52 3.2.6. Análise Estatística 55 4. Resultados 4.1. Padronização da metodologia analítica para quantificação do 5-ALA 4.1.2. Obtenção da curva padrão para o 5-ALA 4. 2. Avaliação dos lipossomos obtidos 4.2.1. Cromatografia de exclusão em gel 4.2.1.1. Determinação do volume morto da coluna 4.2.1.2. Perfil de eluição dos lipossomos vazios (LUVETs e REVs) 59 4.2.1.3. Determinação do perfil de eluição do 5-ALA em solução 4.2.1.4. Determinação do perfil de eluição dos lipossomos (REVs) contendo 5-ALA 63 4.2.1.4.1. Cálculo da porcentagem de 5-ALA encapsulado em lipossomos 4.2.1.5. Determinação do volume de etanol para solubilização das vesículas 4.2.2. Microscopia de luz polarizada 4.2.3. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 4 .3. Calorimetria exploratória diferencial (DSC) 4.4. Estudos in vitro de permeação e retenção cutâneas 4.4.1. Estudos in vitro de permeação cutânea 4.4.2. Estudos in vitro de retenção cutânea 5. Discussão
Brazilian Journal of Pharmaceutical Sciences, 2023
We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodyn... more We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.
: Preparations for topical application are highly important for therapeutic and cosmetic use sinc... more : Preparations for topical application are highly important for therapeutic and cosmetic use since the skin has an extensive and accessible application area. Among the many advantages, this route avoids the systemic effects of the substances and, therefore, fewer adverse reactions are observed. However, the skin is an organ with a remarkable barrier effect, which can compromise the administration of pharmacologically / cosmetologically active molecules. Thus, the skin permeability of substances is a challenge that is only achieved through the preparation of formulations capable of overcoming that same barrier. Nanotechnology was introduced in the pharmaceutical and cosmetic areas to enable the development of systems for the delivery of substances and the optimization of already existing formulations. Among the several benefits and advantages of nanotechnology for topical application is the increased penetration of the drug in the skin, the improvement of the stability of the active, decrease in the active substances (reducing the possible toxic effects and allergic reactions caused by the high concentration of these compounds), and even the intensification of the drug action. This manuscript reviews the topical delivery technologies based on polymeric nanocarriers (PNC) as nanoparticles (NP) and nanogels (NG) and their benefits for better efficacy in most common cutaneous disorders. It starts with skin properties, the aspects for the penetration of active ingredients in the skin and cutaneous penetration challenges, followed by a summary of strategies for skin penetration/permeation of drugs. Then, the focus of the current research was to review NPs and NGs explored for skin disorders management published during the last years.
Photodiagnosis and Photodynamic Therapy, Sep 1, 2021
INTRODUCTION Nanoparticles (Np) can increase drug efficacy well as overcome problems associated w... more INTRODUCTION Nanoparticles (Np) can increase drug efficacy well as overcome problems associated with solubility and aggregation in a solution of PpIX. PURPOSE Evaluate if Np interferes in the photophysical and photobiological capacity of the PpIX comparing with free PpIX intended for topical PDT of melanoma. METHODS In vitro photophysical evaluation of Np-PpIX was carried out through singlet oxygen (1O2) quantum yield. In vitro cytotoxicity and phototoxicity assays have used murine melanoma cell culture. RESULTS The quantum yield of singlet oxygen has shown that Np did not influence the formation capacity of this reactive species. In the dark, all PpIX-Nps concentrations were less cytotoxic compared to free drugs. At a higher light dose (1500 mJ.cm2) 3.91 μg / mL PpIX had similar % viable cells for free and Np (∼34%) meaning Nps did not interfere in the photodynamic effect of PpIX. However, at 7.91 μg / mL the phototoxicity increased for both (5.8 % viable cells for free versus 21.7% for Nps). Despite the higher phototoxicity of free PpIX at this concentration, greater cytotoxicity in the dark was obtained (∼49% viable cells for free versus ∼90.6% Np) which means Nps protect the tumor tissue from the photodynamic action of PpIX. CONCLUSIONS Np is a potential delivery system for melanoma skin cancer, since it maintained the photophysical properties of PpIX and excellent in vitro phototoxicity effect against melanoma cells, reducing cell viability in ∼80% (7.91 μg / mL PpIX in Nps) and safe PDT (due to lower cytotoxicity in the dark).
Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as... more Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as a result of its high specificity for COX-2, without gastrolesivity or interference with platelet function at therapeutic concentrations. Besides of anti-inflammatory effects, Cx also has a potential role for oral cancer chemoprevention. For these conditions, oral administration in long-term treatment is a concern due to its systemic side effects. However, local application at the site of injury (e.g., buccal inflammation conditions or chemoprevention of oral cancer) is a promising way to reduce its toxicity. In this study, the in vitro characterization of mucoadhesive chitosan (CHT) gels associated to Azone® was assessed to explore the potential buccal mucosal administration of Cx in this tissue. Rheological properties of gels were analyzed by a rheometer with cone-plate geometry. In vitro Cx release and permeability studies used artificial membranes and pig cheek mucosa, respectively. Mucoadhesion were measured with a universal test machine. CHT gels (3.0%) containing 2.0% or 3.0% Az showed more appropriate characteristics compared to the others: pH values, rheology, higher amount of Cx retained in the mucosa, and minimal permeation through mucosa, besides the highest mucoadhesion values, ideal for buccal application. Moreover, the flux (J) and amounts of drug released decreased with increased CHT and Az concentrations. CHT gels (3.0%) associated with 2.0% or 3.0% Az may be considered potential delivery systems for buccal administration of Cx.
Brazilian Journal of Pharmaceutical Sciences, Mar 1, 2009
Photodynamic therapy (PDT) based on topical 5-aminolevulinic acid (5-ALA), an endogenous precurso... more Photodynamic therapy (PDT) based on topical 5-aminolevulinic acid (5-ALA), an endogenous precursor of protoporphyrin, is an interesting approach for the treatment of skin cancer. However, 5-ALA is a hydrophilic molecule and such a characteristic limits its appropriate cutaneous penetration and retention. In this way, more lipophilic molecules, such as esterified 5-ALA derivatives, have been under investigation in order to improve the skin penetration of this molecule. Drug formulation can also alter 5-ALA skin penetration. Therefore, the aim of this work was to study the influence of ceramide 2-the main lipid of the SC-on the cutaneous delivery of 5-ALA and its ester derivatives in vitro, using Franz diffusion cell. The skin permeation of all studied drugs was decreased in the presence of ceramide, representing a desirable characteristic in order to avoid the risk of systemic side effects. Nevertheless, the SC and [epidermis + dermis] retention after 16 h has also been decreased in the presence of ceramide, as compared to control. In conclusion, ceramide was not a good adjuvant, meaning that research of other vehicles could be useful to improve cutaneous delivery of 5-ALA. Uniterms: 5-aminolevulinic acid. Ceramide 2. In vitro/Skin permeation. In vitro/Skin retention. Photodynamic therapy. A Terapia Fotodinâmica (TFD) tópica com um precursor das porfirinas endógenas, o ácido 5-aminolevulínico (5-ALA), constitui uma nova modalidade para o tratamento do câncer de pele. Entretanto, o 5-ALA é uma molécula hidrofílica, o que limita sua penetração e retenção cutânea apropriadas. Moléculas mais lipofílicas, tais como derivados esterificados do 5-ALA, estão sob intensa investigação para melhorar a penetração cutânea desta molécula. A formulação que contém o fármaco também pode alterar a penetração cutânea do 5-ALA. Desta forma, o objetivo deste trabalho foi estudar a influência da ceramida 2-o principal lipídeo do EC-sobre a penetração cutânea de 5-ALA e seus derivados esterificados usando células de difusão de Franz. A permeação de todas as drogas estudadas através da pele foi diminuída na presença de ceramida, o que é desejável, evitando riscos de efeitos colaterais sistêmicos. Entretanto, a retenção no EC e [epiderme + derme] também foi diminuída na presença da ceramida, após 16 horas, comparado ao controle. Concluindo, a ceramida não foi um bom adjuvante, sendo necessária a pesquisa de outros veículos para melhorar a liberação cutânea do 5-ALA. Unitermos: Ácido 5-aminolevulínico. Ceramida 2. Permeação cutânea/in vitro. Retenção cutânea/in vitro. Terapia fotodinâmica.
Enhancement strategies are necessary to improve the dermal/transdermal bioavailability of drugs a... more Enhancement strategies are necessary to improve the dermal/transdermal bioavailability of drugs applied to the skin due to its amazing barrier, the stratum corneum. Strategies to overcome this barrier, thus improving drug release to the skin include the use of penetration enhancers, speciWc delivery systems, supersaturated solutions and physical methods (iontophoresis, electroporation and ultrasound). Delivery of active agents to the skin by liposomal carriers has improved topical therapy in the Weld of dermatology. The interest in these carriers is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Particularly, in recent years liposomes have been shown to be a promising drug-delivery system to the skin. Their use may produce several-fold higher drug concentrations in the epidermis and dermis and lower systemic concentrations when compared to conventional dosage forms. On the other hand, special characteristic vesicles like ethosomes, transfersomes and niosomes may be potential transdermal delivery systems for ionic molecules and polypeptides.
Idade de C1enc1as racu. São paulo Uni11ers1dade de Jf. <Profa. (J)ra. :M.aria 'Vitória Lopes <Bad... more Idade de C1enc1as racu. São paulo Uni11ers1dade de Jf. <Profa. (J)ra. :M.aria 'Vitória Lopes <Badra <Bentfey, peta oportuniáaáe áe realização e cresdmento na carreira cientifica, por me acollier com amizaáe em seu grupo áe tra6a0io, peta orientação cuitfadósa e áeáuaáa, !Muito o6ri1Jaáa! AGRADECIMENTOS A todos os amigos do LABORATÓRIO DE FARMACOTÉCNICA E TECNOLOGIA FARMACÊUTICA do Departamento de Ciências Farmacêuticas da FCFRP-USP, pela amizade, apoio, colaboração e auxílios prestados. Ao colega de trabalho e amigo Eduardo Ricci Júnior, pela sua participação e auxílio nos experimentos, pelas sugestões e apoio nos momentos mais difíceis. Ao colega Glauco Henrique Balthazar Nardotto pela sua disponibilidade e colaboração em experimentos. Aos amigos do LABORATÓRIO DE FOTOQUÍMICA E QUÍMICA ORGÂNICA do Departamento de Química da FFCLRP-USP, pela colaboração e auxílios prestados.
Photodynamic Therapy (PDT) is a therapeutic modality used for several malignant and premalignant ... more Photodynamic Therapy (PDT) is a therapeutic modality used for several malignant and premalignant skin disorders, including Bowen's disease skin cancers and Superficial Basal Cell Carcinoma (BCC). Several photosensitizers (PSs) have been explored for tumor destruction of skin cancers, after their activation by a light source of appropriate wavelength. Topical release of PSs avoids prolonged photosensitization reactions associated with systemic administration; however, its clinical usefulness is influenced by its poor tissue penetration and the stability of the active agent. Nanotechnology-based drug delivery systems are promising tool to enhance the efficiency for PDT of cancer. This review focuses on PSs encapsulated in nanocarriers explored for PDT of skin tumors.
Journal of Photochemistry and Photobiology A-chemistry, 2020
The aim of this study was to investigate (i) the cutaneous accumulation of photosensitizer (PS) p... more The aim of this study was to investigate (i) the cutaneous accumulation of photosensitizer (PS) protoporphyrin IX (PpIX) encapsulated in nanoparticles (Np) by confocal laser scanning microscopy (CLSM) in animal model skin (ii) the in vitro dark cytotoxicity and phototoxicity of PpIX-Nps in dermal fibroblast cells (L929 fibroblast cells and (iii) the recovery of cell viability after PDT. The CLSM has shown higher PS concentration in the superficial skin; the stratum corneum (SC) for both encapsulated and free PpIX for all times evaluated (4 h, 8 h and 24 h). Although with lower PS accumulation in the deeper layers of the skin, ie; Epidermis + Dermis (EP + D) after 8 h the PS accumulation was significantly higher when encapsulated in Np. In brief, PpIX-Np was not cytotoxic to fibroblast cells in the dark (˜100% viable cells; excellent biocompatibility) and in the presence of light 8 h post incubation (phototoxicity) reached CC 50 = 7.01 μg / ml (compared to free PpIX, CC 50 = 0.84 μg / ml) meaning that PpIX in Nps were phototoxic to cells as expected; however at higher concentrations than free PpIX. Moreover, PpIX-Np has shown 100% of cell recovery 24 h post PDT in the fibroblast cells, indicating photoactivation protection of PpIX by the Nps in the healthy cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and particularly selective cyclooxygenase-2 (COX-2)... more Nonsteroidal anti-inflammatory drugs (NSAIDs) and particularly selective cyclooxygenase-2 (COX-2) inhibitors such as celecoxib (Cxb) are considered promising cancer chemopreventive for colon, breast, prostate, lung, and skin cancers. However, the clinical application to the prevention is limited by concerns about safety, potential to serious toxicity (mainly for healthy individuals), efficacy and optimal treatment regimen. Cxb exhibits advantages as potent anti-inflammatory and gastrointestinal tolerance compared with conventional NSAID&#39;s. Recent researches suggest that dermatological formulations of Cxb are more suitable than oral administration in treatment of cutaneous disease, including skin cancer. To date optimism has been growing regarding the exploration of the topical application of Cxb (in the prevention of skin cancers and treatment of cutaneous inflammation) or transdermal route reducing risks of systemic side effects. This paper briefly summarizes our current knowledge of the development of the cutaneous formulations or delivery systems for Cxb as anti-inflammatory drug (for topical or transdermal application) as well its chemopreventive properties focused on skin cancer. new perspectives emerge from the growing knowledge, bringing innovative techniques combining the action of Cxb with other substances or agents which act in a different way, but complementary, increasing the efficacy and minimizing toxicity.
Journal of Pharmacy and Pharmaceutical Sciences, Aug 24, 2010
Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to av... more Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to avoid the side effects associated with systemic delivery, but it is ineffective due to the drug poor skin penetration. We have investigated the effects of oleic acid (OA), a lipid penetration enhancer, on the in vitro release of LM from poloxamer-based delivery systems (PBDS). The rheological behavior (shear rate dependent viscosity) and gelation temperature through measurements of optimal sol-gel transition temperatures (T sol-gel) were also carried out in these systems. Methods. In vitro release studies of LM from PBDS were performed using cellulose acetate as artificial membrane mounted in a diffusion system. The amount of LM released was divided by exposition area (µg/cm 2) and these values were plotted as function of the time (h). The flux of the drug across the membrane (J) was calculated from the slope of the linear portion of the plot and expressed as µg/cm 2 /h. The determination of viscosity was carried out at different shear rates (γ) between 0.1-1000 S-1 using a parallel plate rheometer. Oscillatory measurements using a cone-plate geometry rheometer surrounded by a double jacket with temperature varying 4-40°C, was used in order to determine T sol-gel. Results. Increase of both polymer and OA concentrations increases the viscosity of the gels and consequently reduces the in vitro LM release from the PBDS, mainly for gels containing OA at 10.0% (w/w) compared to other concentrations of the penetration enhancer. T sol-gel transition temperature was decreased by increasing viscosity; in some cases the formulation was already a gel at room temperature. Rheological studies showed a pseudoplastic behavior, which facilitates the flow and improves the spreading characteristics of the formulations. Conclusions. Taken together, the results showed that poloxamer gels are good potential delivery systems for LM, leading to a sustained release, and also have appropriate rheological characteristics.
. "For me my research represents much more than three lines in my CV. It raised questions which I... more . "For me my research represents much more than three lines in my CV. It raised questions which I answered. It was a test which I passed. A battle which I won. It was an experience ingrained with long days and nights, and many tears of frustation. It was a work ethic and way of thinking that will be me forever. descongelamento (LUVETs) seguido por extrusão 3.2.2.2. Obtenção dos lipossomos por técnica de fase reversa (REVs) 3.2.3. Avaliação dos lipossomos obtidos 3.2.3.1. Caracterização dos lipossomos vazios (LUVETs e REVs) por cromatografia de exclusão em gel. 3.2.3.2. Caracterização dos lipossomos contendo 5-ALA (REVs) por cromatografia de exclusão em gel a) Determinação do perfil de eluição do 5-ALA em solução b) Determinação do perfil de eluição dos lipossomos com 5-ALA e) Determinação do volume de etanol para a solubilização das vesículas lipossômicas 3.2.3.3. Microscopia de luz polarizada 3.2.3.4. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 3.2.4. Calorimetria Exploratória Diferencial (DSC) 3.2.4.1. Obtenção dos filmes lipídicos para análise de DSC 3.2.5. Estudos in vitro de permeação e retenção cutâneas 50 50 51 52 3.2.6. Análise Estatística 55 4. Resultados 4.1. Padronização da metodologia analítica para quantificação do 5-ALA 4.1.2. Obtenção da curva padrão para o 5-ALA 4. 2. Avaliação dos lipossomos obtidos 4.2.1. Cromatografia de exclusão em gel 4.2.1.1. Determinação do volume morto da coluna 4.2.1.2. Perfil de eluição dos lipossomos vazios (LUVETs e REVs) 59 4.2.1.3. Determinação do perfil de eluição do 5-ALA em solução 4.2.1.4. Determinação do perfil de eluição dos lipossomos (REVs) contendo 5-ALA 63 4.2.1.4.1. Cálculo da porcentagem de 5-ALA encapsulado em lipossomos 4.2.1.5. Determinação do volume de etanol para solubilização das vesículas 4.2.2. Microscopia de luz polarizada 4.2.3. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 4 .3. Calorimetria exploratória diferencial (DSC) 4.4. Estudos in vitro de permeação e retenção cutâneas 4.4.1. Estudos in vitro de permeação cutânea 4.4.2. Estudos in vitro de retenção cutânea 5. Discussão
BACKGROUND Use of topical or transdermal administration of Celecoxib (Cxb) is an interesting stra... more BACKGROUND Use of topical or transdermal administration of Celecoxib (Cxb) is an interesting strategy in cutaneous treatments since it reduces or avoids side effects of the oral route. However, Cxb´s high lipophilicity and the stratum corneum (SC) barrier impair cutaneous penetration. OBJECTIVE Evaluation of copaiba oil (C.O) as a potential skin penetration enhancer (P.E) for Cxb. METHODS The chemical composition of C.O was evaluated by GC-MS. Both in-vitro release and permeability assay of Cxb in Polyethylene glycol 400/ propylene glycol (PEG 400/PG) vehicle associated to C.O (1-50% w/w) were determined in a modified diffusion cell fitted with a synthetic hydrophobic membrane and pig ear skin as model, respectively. RESULTS GC-MS analysis of C.O showed that it is composed of sesquiterpenes (68.65%) and diterpenes (22.26%). Formulations containing 25% C.O (F4) and 50% C.O (F5) have shown in-vitro burst release in the first 2 h, but only F4 released 100% of drug after 24 h. The highest Cxb permeation across skin was obtained from F4 and the highest skin retentions for F4 and F5 in the stratum corneum and epidermis plus dermis. CONCLUSION The increased Cxb permeability through skin and its retention for an extended time (24h) at 25% C.O suggest that it could be a promising adjuvant for the development of transdermal formulations of Cxb.
Revista de Ciências Farmacêuticas Básica e Aplicada, Aug 5, 2009
ABSTRACT In this study, two methods, based on highperformance liquid chromatography (HPLC) and UV... more ABSTRACT In this study, two methods, based on highperformance liquid chromatography (HPLC) and UV spectrophotometry, were developed and validated for the quantitative determination of lumiracoxib in tablets. The HPLC was carried out on a column of propylsulfonic acid bonded to silica gel (250 x 4.6 mm; 5 μm), with a mobile phase of phosphate buffer (pH 7.4; 10 mM)-water-acetonitrile (10:40:50, v/v/v) fl owing at 1.0 mL/min and detection of the drug at 278 nm. The UV method was based on absorbance at 275 nm, with ethanol as solvent. Both assays were linear over the concentration range of 2–30 μg/mL (R≈0.999), as well as accurate and precise, with recoveries between 98 and 100% and relative standard deviation (%RSD) &lt; 2.0%. The proposed methods are highly sensitive, precise and accurate and were successfully applied to the quantitation of lumiracoxib in the commercial formulation. The spectrophotometric method is a simple, cheap and less time-consuming method. However, the chromatographic method is selective for the determination of the degradation products of lumiracoxib. Keywords: lumiracoxib; tablets; HPLC; UV spectrophotometry; pharmaceutical analyses.
Photodiagnosis and Photodynamic Therapy, Mar 1, 2015
Please cite this article in press as: Graciano TB, et al. Using chitosan gels as a toluidine blue... more Please cite this article in press as: Graciano TB, et al. Using chitosan gels as a toluidine blue O delivery system for photodynamic therapy of buccal cancer: In vitro and in vivo studies. Photodiagnosis and Photodynamic Therapy (2014),
A esporotricose, uma doença fúngica causada pelo Sporothrix e afetando tanto humanos quanto felin... more A esporotricose, uma doença fúngica causada pelo Sporothrix e afetando tanto humanos quanto felinos, é comumente tratada com Itraconazol oral por períodos prolongados, porém a crescente resistência ao antifúngico decorrente de interrupções no tratamento tem sido observada. Diante desse cenário, os óleos essenciais e extratos de plantas surgem como potenciais alternativas terapêuticas mais eficazes em comparação aos fármacos existentes. O objetivo desta revisão é oferecer uma visão abrangente e atualizada sobre óleos e extratos vegetais contra cepas de Sporothrix spp., que possam contribuir futuramente para o desenvolvimento de terapias mais eficazes e seguras para essa importante zoonose. Os estudos in vitro avaliaram a ação fungistática pela determinação da Concentração Inibitória Mínima (CIM) e a ação fungicida pela determinação da Concentração Fungicida Mínima (CFM), este ultimo incluindo estudos de viabilidade celular. Os estudos in vivo em modelo animal, no geral determinaram a redução dos sintomas da doença e carga fúngica, remissão dos sintomas clínicos e disseminação do fungo para órgãos. Os estudos analisados indicaram que esses compostos vegetais têm potencial eficácia contra o fungo, especialmente para as cepas de S. brasiliensis e S. schenckii, entretanto é necessário uma padronização metodológica para comparação adequada dos resultados. Em geral, a utilização futura destes antifúngicos naturais em formulações orais ou tópicas pode representar um avanço significativo no tratamento da esporotricose felina, minimizando suas complicações.
Journal of Pharmacy and Pharmacology, Mar 29, 2018
Objectives The aim of this article was to use copaiba oil (C.O) to improve skin permeability and ... more Objectives The aim of this article was to use copaiba oil (C.O) to improve skin permeability and topical anti-inflammatory activity of celecoxib (Cxb). Methods Formulations containing C.O (1-50%) were associated with Cxb (2%). In vitro skin permeability studies were conducted using porcine ear skin. Histological analysis of the hairless mice skin samples after application of formulations was achieved with the routine haematoxylin/eosin technique. The anti-inflammatory activity was assessed using the AA-induced ear oedema mice model. Key findings The formulation containing 25% C.O promoted the highest levels of in vitro Cxb permeation through pig ear skin, retention in the stratum corneum (SC) and epidermis/dermis of pig ear skin in vitro (~5-fold) and hairless mice skin in vivo (~2.0-fold), as compared with the control formulation. At 25%, C.O caused SC disorganization and increased cell infiltration and induced angiogenesis without clear signs of skin irritation. The formulation added to 25% C.O as adjuvant inhibited ear oedema and protein extravasation by 77.51 and 89.7%, respectively, and that it was, respectively, 2.0-and 3.4-fold more efficient than the commercial diethylammonium diclofenac cream gel to suppress these inflammatory parameters. Conclusions 25% C.O is a potential penetration enhancer for lipophilic drugs like Cxb that can improve cutaneous drug penetration and its anti-inflammatory activity.
. "For me my research represents much more than three lines in my CV. It raised questions which I... more . "For me my research represents much more than three lines in my CV. It raised questions which I answered. It was a test which I passed. A battle which I won. It was an experience ingrained with long days and nights, and many tears of frustation. It was a work ethic and way of thinking that will be me forever. descongelamento (LUVETs) seguido por extrusão 3.2.2.2. Obtenção dos lipossomos por técnica de fase reversa (REVs) 3.2.3. Avaliação dos lipossomos obtidos 3.2.3.1. Caracterização dos lipossomos vazios (LUVETs e REVs) por cromatografia de exclusão em gel. 3.2.3.2. Caracterização dos lipossomos contendo 5-ALA (REVs) por cromatografia de exclusão em gel a) Determinação do perfil de eluição do 5-ALA em solução b) Determinação do perfil de eluição dos lipossomos com 5-ALA e) Determinação do volume de etanol para a solubilização das vesículas lipossômicas 3.2.3.3. Microscopia de luz polarizada 3.2.3.4. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 3.2.4. Calorimetria Exploratória Diferencial (DSC) 3.2.4.1. Obtenção dos filmes lipídicos para análise de DSC 3.2.5. Estudos in vitro de permeação e retenção cutâneas 50 50 51 52 3.2.6. Análise Estatística 55 4. Resultados 4.1. Padronização da metodologia analítica para quantificação do 5-ALA 4.1.2. Obtenção da curva padrão para o 5-ALA 4. 2. Avaliação dos lipossomos obtidos 4.2.1. Cromatografia de exclusão em gel 4.2.1.1. Determinação do volume morto da coluna 4.2.1.2. Perfil de eluição dos lipossomos vazios (LUVETs e REVs) 59 4.2.1.3. Determinação do perfil de eluição do 5-ALA em solução 4.2.1.4. Determinação do perfil de eluição dos lipossomos (REVs) contendo 5-ALA 63 4.2.1.4.1. Cálculo da porcentagem de 5-ALA encapsulado em lipossomos 4.2.1.5. Determinação do volume de etanol para solubilização das vesículas 4.2.2. Microscopia de luz polarizada 4.2.3. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 4 .3. Calorimetria exploratória diferencial (DSC) 4.4. Estudos in vitro de permeação e retenção cutâneas 4.4.1. Estudos in vitro de permeação cutânea 4.4.2. Estudos in vitro de retenção cutânea 5. Discussão
Brazilian Journal of Pharmaceutical Sciences, 2023
We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodyn... more We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.
: Preparations for topical application are highly important for therapeutic and cosmetic use sinc... more : Preparations for topical application are highly important for therapeutic and cosmetic use since the skin has an extensive and accessible application area. Among the many advantages, this route avoids the systemic effects of the substances and, therefore, fewer adverse reactions are observed. However, the skin is an organ with a remarkable barrier effect, which can compromise the administration of pharmacologically / cosmetologically active molecules. Thus, the skin permeability of substances is a challenge that is only achieved through the preparation of formulations capable of overcoming that same barrier. Nanotechnology was introduced in the pharmaceutical and cosmetic areas to enable the development of systems for the delivery of substances and the optimization of already existing formulations. Among the several benefits and advantages of nanotechnology for topical application is the increased penetration of the drug in the skin, the improvement of the stability of the active, decrease in the active substances (reducing the possible toxic effects and allergic reactions caused by the high concentration of these compounds), and even the intensification of the drug action. This manuscript reviews the topical delivery technologies based on polymeric nanocarriers (PNC) as nanoparticles (NP) and nanogels (NG) and their benefits for better efficacy in most common cutaneous disorders. It starts with skin properties, the aspects for the penetration of active ingredients in the skin and cutaneous penetration challenges, followed by a summary of strategies for skin penetration/permeation of drugs. Then, the focus of the current research was to review NPs and NGs explored for skin disorders management published during the last years.
Photodiagnosis and Photodynamic Therapy, Sep 1, 2021
INTRODUCTION Nanoparticles (Np) can increase drug efficacy well as overcome problems associated w... more INTRODUCTION Nanoparticles (Np) can increase drug efficacy well as overcome problems associated with solubility and aggregation in a solution of PpIX. PURPOSE Evaluate if Np interferes in the photophysical and photobiological capacity of the PpIX comparing with free PpIX intended for topical PDT of melanoma. METHODS In vitro photophysical evaluation of Np-PpIX was carried out through singlet oxygen (1O2) quantum yield. In vitro cytotoxicity and phototoxicity assays have used murine melanoma cell culture. RESULTS The quantum yield of singlet oxygen has shown that Np did not influence the formation capacity of this reactive species. In the dark, all PpIX-Nps concentrations were less cytotoxic compared to free drugs. At a higher light dose (1500 mJ.cm2) 3.91 μg / mL PpIX had similar % viable cells for free and Np (∼34%) meaning Nps did not interfere in the photodynamic effect of PpIX. However, at 7.91 μg / mL the phototoxicity increased for both (5.8 % viable cells for free versus 21.7% for Nps). Despite the higher phototoxicity of free PpIX at this concentration, greater cytotoxicity in the dark was obtained (∼49% viable cells for free versus ∼90.6% Np) which means Nps protect the tumor tissue from the photodynamic action of PpIX. CONCLUSIONS Np is a potential delivery system for melanoma skin cancer, since it maintained the photophysical properties of PpIX and excellent in vitro phototoxicity effect against melanoma cells, reducing cell viability in ∼80% (7.91 μg / mL PpIX in Nps) and safe PDT (due to lower cytotoxicity in the dark).
Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as... more Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as a result of its high specificity for COX-2, without gastrolesivity or interference with platelet function at therapeutic concentrations. Besides of anti-inflammatory effects, Cx also has a potential role for oral cancer chemoprevention. For these conditions, oral administration in long-term treatment is a concern due to its systemic side effects. However, local application at the site of injury (e.g., buccal inflammation conditions or chemoprevention of oral cancer) is a promising way to reduce its toxicity. In this study, the in vitro characterization of mucoadhesive chitosan (CHT) gels associated to Azone® was assessed to explore the potential buccal mucosal administration of Cx in this tissue. Rheological properties of gels were analyzed by a rheometer with cone-plate geometry. In vitro Cx release and permeability studies used artificial membranes and pig cheek mucosa, respectively. Mucoadhesion were measured with a universal test machine. CHT gels (3.0%) containing 2.0% or 3.0% Az showed more appropriate characteristics compared to the others: pH values, rheology, higher amount of Cx retained in the mucosa, and minimal permeation through mucosa, besides the highest mucoadhesion values, ideal for buccal application. Moreover, the flux (J) and amounts of drug released decreased with increased CHT and Az concentrations. CHT gels (3.0%) associated with 2.0% or 3.0% Az may be considered potential delivery systems for buccal administration of Cx.
Brazilian Journal of Pharmaceutical Sciences, Mar 1, 2009
Photodynamic therapy (PDT) based on topical 5-aminolevulinic acid (5-ALA), an endogenous precurso... more Photodynamic therapy (PDT) based on topical 5-aminolevulinic acid (5-ALA), an endogenous precursor of protoporphyrin, is an interesting approach for the treatment of skin cancer. However, 5-ALA is a hydrophilic molecule and such a characteristic limits its appropriate cutaneous penetration and retention. In this way, more lipophilic molecules, such as esterified 5-ALA derivatives, have been under investigation in order to improve the skin penetration of this molecule. Drug formulation can also alter 5-ALA skin penetration. Therefore, the aim of this work was to study the influence of ceramide 2-the main lipid of the SC-on the cutaneous delivery of 5-ALA and its ester derivatives in vitro, using Franz diffusion cell. The skin permeation of all studied drugs was decreased in the presence of ceramide, representing a desirable characteristic in order to avoid the risk of systemic side effects. Nevertheless, the SC and [epidermis + dermis] retention after 16 h has also been decreased in the presence of ceramide, as compared to control. In conclusion, ceramide was not a good adjuvant, meaning that research of other vehicles could be useful to improve cutaneous delivery of 5-ALA. Uniterms: 5-aminolevulinic acid. Ceramide 2. In vitro/Skin permeation. In vitro/Skin retention. Photodynamic therapy. A Terapia Fotodinâmica (TFD) tópica com um precursor das porfirinas endógenas, o ácido 5-aminolevulínico (5-ALA), constitui uma nova modalidade para o tratamento do câncer de pele. Entretanto, o 5-ALA é uma molécula hidrofílica, o que limita sua penetração e retenção cutânea apropriadas. Moléculas mais lipofílicas, tais como derivados esterificados do 5-ALA, estão sob intensa investigação para melhorar a penetração cutânea desta molécula. A formulação que contém o fármaco também pode alterar a penetração cutânea do 5-ALA. Desta forma, o objetivo deste trabalho foi estudar a influência da ceramida 2-o principal lipídeo do EC-sobre a penetração cutânea de 5-ALA e seus derivados esterificados usando células de difusão de Franz. A permeação de todas as drogas estudadas através da pele foi diminuída na presença de ceramida, o que é desejável, evitando riscos de efeitos colaterais sistêmicos. Entretanto, a retenção no EC e [epiderme + derme] também foi diminuída na presença da ceramida, após 16 horas, comparado ao controle. Concluindo, a ceramida não foi um bom adjuvante, sendo necessária a pesquisa de outros veículos para melhorar a liberação cutânea do 5-ALA. Unitermos: Ácido 5-aminolevulínico. Ceramida 2. Permeação cutânea/in vitro. Retenção cutânea/in vitro. Terapia fotodinâmica.
Enhancement strategies are necessary to improve the dermal/transdermal bioavailability of drugs a... more Enhancement strategies are necessary to improve the dermal/transdermal bioavailability of drugs applied to the skin due to its amazing barrier, the stratum corneum. Strategies to overcome this barrier, thus improving drug release to the skin include the use of penetration enhancers, speciWc delivery systems, supersaturated solutions and physical methods (iontophoresis, electroporation and ultrasound). Delivery of active agents to the skin by liposomal carriers has improved topical therapy in the Weld of dermatology. The interest in these carriers is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Particularly, in recent years liposomes have been shown to be a promising drug-delivery system to the skin. Their use may produce several-fold higher drug concentrations in the epidermis and dermis and lower systemic concentrations when compared to conventional dosage forms. On the other hand, special characteristic vesicles like ethosomes, transfersomes and niosomes may be potential transdermal delivery systems for ionic molecules and polypeptides.
Idade de C1enc1as racu. São paulo Uni11ers1dade de Jf. <Profa. (J)ra. :M.aria 'Vitória Lopes <Bad... more Idade de C1enc1as racu. São paulo Uni11ers1dade de Jf. <Profa. (J)ra. :M.aria 'Vitória Lopes <Badra <Bentfey, peta oportuniáaáe áe realização e cresdmento na carreira cientifica, por me acollier com amizaáe em seu grupo áe tra6a0io, peta orientação cuitfadósa e áeáuaáa, !Muito o6ri1Jaáa! AGRADECIMENTOS A todos os amigos do LABORATÓRIO DE FARMACOTÉCNICA E TECNOLOGIA FARMACÊUTICA do Departamento de Ciências Farmacêuticas da FCFRP-USP, pela amizade, apoio, colaboração e auxílios prestados. Ao colega de trabalho e amigo Eduardo Ricci Júnior, pela sua participação e auxílio nos experimentos, pelas sugestões e apoio nos momentos mais difíceis. Ao colega Glauco Henrique Balthazar Nardotto pela sua disponibilidade e colaboração em experimentos. Aos amigos do LABORATÓRIO DE FOTOQUÍMICA E QUÍMICA ORGÂNICA do Departamento de Química da FFCLRP-USP, pela colaboração e auxílios prestados.
Photodynamic Therapy (PDT) is a therapeutic modality used for several malignant and premalignant ... more Photodynamic Therapy (PDT) is a therapeutic modality used for several malignant and premalignant skin disorders, including Bowen's disease skin cancers and Superficial Basal Cell Carcinoma (BCC). Several photosensitizers (PSs) have been explored for tumor destruction of skin cancers, after their activation by a light source of appropriate wavelength. Topical release of PSs avoids prolonged photosensitization reactions associated with systemic administration; however, its clinical usefulness is influenced by its poor tissue penetration and the stability of the active agent. Nanotechnology-based drug delivery systems are promising tool to enhance the efficiency for PDT of cancer. This review focuses on PSs encapsulated in nanocarriers explored for PDT of skin tumors.
Journal of Photochemistry and Photobiology A-chemistry, 2020
The aim of this study was to investigate (i) the cutaneous accumulation of photosensitizer (PS) p... more The aim of this study was to investigate (i) the cutaneous accumulation of photosensitizer (PS) protoporphyrin IX (PpIX) encapsulated in nanoparticles (Np) by confocal laser scanning microscopy (CLSM) in animal model skin (ii) the in vitro dark cytotoxicity and phototoxicity of PpIX-Nps in dermal fibroblast cells (L929 fibroblast cells and (iii) the recovery of cell viability after PDT. The CLSM has shown higher PS concentration in the superficial skin; the stratum corneum (SC) for both encapsulated and free PpIX for all times evaluated (4 h, 8 h and 24 h). Although with lower PS accumulation in the deeper layers of the skin, ie; Epidermis + Dermis (EP + D) after 8 h the PS accumulation was significantly higher when encapsulated in Np. In brief, PpIX-Np was not cytotoxic to fibroblast cells in the dark (˜100% viable cells; excellent biocompatibility) and in the presence of light 8 h post incubation (phototoxicity) reached CC 50 = 7.01 μg / ml (compared to free PpIX, CC 50 = 0.84 μg / ml) meaning that PpIX in Nps were phototoxic to cells as expected; however at higher concentrations than free PpIX. Moreover, PpIX-Np has shown 100% of cell recovery 24 h post PDT in the fibroblast cells, indicating photoactivation protection of PpIX by the Nps in the healthy cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and particularly selective cyclooxygenase-2 (COX-2)... more Nonsteroidal anti-inflammatory drugs (NSAIDs) and particularly selective cyclooxygenase-2 (COX-2) inhibitors such as celecoxib (Cxb) are considered promising cancer chemopreventive for colon, breast, prostate, lung, and skin cancers. However, the clinical application to the prevention is limited by concerns about safety, potential to serious toxicity (mainly for healthy individuals), efficacy and optimal treatment regimen. Cxb exhibits advantages as potent anti-inflammatory and gastrointestinal tolerance compared with conventional NSAID&#39;s. Recent researches suggest that dermatological formulations of Cxb are more suitable than oral administration in treatment of cutaneous disease, including skin cancer. To date optimism has been growing regarding the exploration of the topical application of Cxb (in the prevention of skin cancers and treatment of cutaneous inflammation) or transdermal route reducing risks of systemic side effects. This paper briefly summarizes our current knowledge of the development of the cutaneous formulations or delivery systems for Cxb as anti-inflammatory drug (for topical or transdermal application) as well its chemopreventive properties focused on skin cancer. new perspectives emerge from the growing knowledge, bringing innovative techniques combining the action of Cxb with other substances or agents which act in a different way, but complementary, increasing the efficacy and minimizing toxicity.
Journal of Pharmacy and Pharmaceutical Sciences, Aug 24, 2010
Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to av... more Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to avoid the side effects associated with systemic delivery, but it is ineffective due to the drug poor skin penetration. We have investigated the effects of oleic acid (OA), a lipid penetration enhancer, on the in vitro release of LM from poloxamer-based delivery systems (PBDS). The rheological behavior (shear rate dependent viscosity) and gelation temperature through measurements of optimal sol-gel transition temperatures (T sol-gel) were also carried out in these systems. Methods. In vitro release studies of LM from PBDS were performed using cellulose acetate as artificial membrane mounted in a diffusion system. The amount of LM released was divided by exposition area (µg/cm 2) and these values were plotted as function of the time (h). The flux of the drug across the membrane (J) was calculated from the slope of the linear portion of the plot and expressed as µg/cm 2 /h. The determination of viscosity was carried out at different shear rates (γ) between 0.1-1000 S-1 using a parallel plate rheometer. Oscillatory measurements using a cone-plate geometry rheometer surrounded by a double jacket with temperature varying 4-40°C, was used in order to determine T sol-gel. Results. Increase of both polymer and OA concentrations increases the viscosity of the gels and consequently reduces the in vitro LM release from the PBDS, mainly for gels containing OA at 10.0% (w/w) compared to other concentrations of the penetration enhancer. T sol-gel transition temperature was decreased by increasing viscosity; in some cases the formulation was already a gel at room temperature. Rheological studies showed a pseudoplastic behavior, which facilitates the flow and improves the spreading characteristics of the formulations. Conclusions. Taken together, the results showed that poloxamer gels are good potential delivery systems for LM, leading to a sustained release, and also have appropriate rheological characteristics.
. "For me my research represents much more than three lines in my CV. It raised questions which I... more . "For me my research represents much more than three lines in my CV. It raised questions which I answered. It was a test which I passed. A battle which I won. It was an experience ingrained with long days and nights, and many tears of frustation. It was a work ethic and way of thinking that will be me forever. descongelamento (LUVETs) seguido por extrusão 3.2.2.2. Obtenção dos lipossomos por técnica de fase reversa (REVs) 3.2.3. Avaliação dos lipossomos obtidos 3.2.3.1. Caracterização dos lipossomos vazios (LUVETs e REVs) por cromatografia de exclusão em gel. 3.2.3.2. Caracterização dos lipossomos contendo 5-ALA (REVs) por cromatografia de exclusão em gel a) Determinação do perfil de eluição do 5-ALA em solução b) Determinação do perfil de eluição dos lipossomos com 5-ALA e) Determinação do volume de etanol para a solubilização das vesículas lipossômicas 3.2.3.3. Microscopia de luz polarizada 3.2.3.4. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 3.2.4. Calorimetria Exploratória Diferencial (DSC) 3.2.4.1. Obtenção dos filmes lipídicos para análise de DSC 3.2.5. Estudos in vitro de permeação e retenção cutâneas 50 50 51 52 3.2.6. Análise Estatística 55 4. Resultados 4.1. Padronização da metodologia analítica para quantificação do 5-ALA 4.1.2. Obtenção da curva padrão para o 5-ALA 4. 2. Avaliação dos lipossomos obtidos 4.2.1. Cromatografia de exclusão em gel 4.2.1.1. Determinação do volume morto da coluna 4.2.1.2. Perfil de eluição dos lipossomos vazios (LUVETs e REVs) 59 4.2.1.3. Determinação do perfil de eluição do 5-ALA em solução 4.2.1.4. Determinação do perfil de eluição dos lipossomos (REVs) contendo 5-ALA 63 4.2.1.4.1. Cálculo da porcentagem de 5-ALA encapsulado em lipossomos 4.2.1.5. Determinação do volume de etanol para solubilização das vesículas 4.2.2. Microscopia de luz polarizada 4.2.3. Determinação do tamanho das vesículas por Espalhamento Dinâmico da Luz 4 .3. Calorimetria exploratória diferencial (DSC) 4.4. Estudos in vitro de permeação e retenção cutâneas 4.4.1. Estudos in vitro de permeação cutânea 4.4.2. Estudos in vitro de retenção cutânea 5. Discussão
BACKGROUND Use of topical or transdermal administration of Celecoxib (Cxb) is an interesting stra... more BACKGROUND Use of topical or transdermal administration of Celecoxib (Cxb) is an interesting strategy in cutaneous treatments since it reduces or avoids side effects of the oral route. However, Cxb´s high lipophilicity and the stratum corneum (SC) barrier impair cutaneous penetration. OBJECTIVE Evaluation of copaiba oil (C.O) as a potential skin penetration enhancer (P.E) for Cxb. METHODS The chemical composition of C.O was evaluated by GC-MS. Both in-vitro release and permeability assay of Cxb in Polyethylene glycol 400/ propylene glycol (PEG 400/PG) vehicle associated to C.O (1-50% w/w) were determined in a modified diffusion cell fitted with a synthetic hydrophobic membrane and pig ear skin as model, respectively. RESULTS GC-MS analysis of C.O showed that it is composed of sesquiterpenes (68.65%) and diterpenes (22.26%). Formulations containing 25% C.O (F4) and 50% C.O (F5) have shown in-vitro burst release in the first 2 h, but only F4 released 100% of drug after 24 h. The highest Cxb permeation across skin was obtained from F4 and the highest skin retentions for F4 and F5 in the stratum corneum and epidermis plus dermis. CONCLUSION The increased Cxb permeability through skin and its retention for an extended time (24h) at 25% C.O suggest that it could be a promising adjuvant for the development of transdermal formulations of Cxb.
Revista de Ciências Farmacêuticas Básica e Aplicada, Aug 5, 2009
ABSTRACT In this study, two methods, based on highperformance liquid chromatography (HPLC) and UV... more ABSTRACT In this study, two methods, based on highperformance liquid chromatography (HPLC) and UV spectrophotometry, were developed and validated for the quantitative determination of lumiracoxib in tablets. The HPLC was carried out on a column of propylsulfonic acid bonded to silica gel (250 x 4.6 mm; 5 μm), with a mobile phase of phosphate buffer (pH 7.4; 10 mM)-water-acetonitrile (10:40:50, v/v/v) fl owing at 1.0 mL/min and detection of the drug at 278 nm. The UV method was based on absorbance at 275 nm, with ethanol as solvent. Both assays were linear over the concentration range of 2–30 μg/mL (R≈0.999), as well as accurate and precise, with recoveries between 98 and 100% and relative standard deviation (%RSD) &lt; 2.0%. The proposed methods are highly sensitive, precise and accurate and were successfully applied to the quantitation of lumiracoxib in the commercial formulation. The spectrophotometric method is a simple, cheap and less time-consuming method. However, the chromatographic method is selective for the determination of the degradation products of lumiracoxib. Keywords: lumiracoxib; tablets; HPLC; UV spectrophotometry; pharmaceutical analyses.
Photodiagnosis and Photodynamic Therapy, Mar 1, 2015
Please cite this article in press as: Graciano TB, et al. Using chitosan gels as a toluidine blue... more Please cite this article in press as: Graciano TB, et al. Using chitosan gels as a toluidine blue O delivery system for photodynamic therapy of buccal cancer: In vitro and in vivo studies. Photodiagnosis and Photodynamic Therapy (2014),
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