RESUMO
Vulvovaginal candidiasis is a public health problem with a high incidence among female patients. Currently, there is an increase in the identification of Candida spp. resistant to current therapy, making it necessary to search for new therapeutic alternatives. The synergistic potential of curcumin with fluconazole is described in the literature. However, due to its high lipophilicity, it is necessary to use drug-delivery systems to adequately explore its potential, among which is the nanostructured lipid carrier. However, to date, there is no validated method of high-performance liquid chromatography for simultaneous determination of fluconazole and curcumin in the literature. Thus, the present work developed a high-performance liquid chromatography method for simultaneous determination of fluconazole and curcumin co-encapsulated in nanostructured lipid carrier which was validated according to the International Conference on Harmonization (Technical Requirements for Registration of Pharmaceuticals for Human Use) - Q2 (R1) and the Food and Drug Administration - Guidance for Bioanalytical Method. The method was applied to determine the encapsulation efficiency and drug-loading of curcumin and fluconazole in nanostructured lipid carriers. The developed method proved to be selective, precise, accurate, and robust for the simultaneous determination of both drugs, enabling the quantification of encapsulation efficiency and drug-loading of curcumin and fluconazole in nanostructured lipid carriers.
Assuntos
Curcumina/análise , Fluconazol/análise , Lipídeos/química , Nanoestruturas/química , Cromatografia Líquida de Alta PressãoRESUMO
Owing to the growing resistance among isolates of Candida species to usual antifungal agents and the well-known therapeutic potential of curcumin, the purpose of this study was to develop and validate a vaginal formulation containing this substance and to evaluating its effectiveness in the treatment of experimental vulvovaginal candidiasis. Curcumin was incorporated in a vaginal cream in three concentrations (0.01%, 0.1% and 1.0%). The different concentrations of the cream and its controls were intravaginally administered in an immunosuppressed rat model to evaluate the efficacy in the treatment of experimental vulvovaginal candidiasis. Samples of the cream were also subjected to centrifugation and physical stability tests and an analytical method for quantification of curcumin was validated based on HPLC. The formulation was stable and the HPLC method could be considered suitable for the quantitative determination of curcumin in the cream. After 6 days of preclinical study, the number of infected animals was 1/6 in all groups treated with curcumin vaginal cream and the fungal burden showed a progressive reduction. Reduction in the inflammatory infiltrate was observed in the group treated with 1.0% cream. Vaginal cream containing curcumin could be considered a promising effective antifungal medicine in the treatment of vulvovaginal candidiasis.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Curcumina/administração & dosagem , Cremes, Espumas e Géis Vaginais/administração & dosagem , Animais , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/patologia , Centrifugação , Cromatografia Líquida de Alta Pressão , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Estabilidade de Medicamentos , Feminino , Ratos Wistar , Resultado do TratamentoRESUMO
Microemulsions (MEs) loaded with methyl dihydrojasmonate (MJ) were developed to improve the aqueous solubility of this drug. The composition of the formulations ranged according to the oil/surfactant ratio (O/S). The MEs were characterized according to diameter of droplets, X-ray diffraction and polarized light microscopy. The MJ identification and quantification was performed by gas chromatography-mass spectrometry (GC-MS). The MJ showed a retention time of â¼16.7 min for all samples. The obtained correlation coefficient from the calibration graph was 0.991. The developed analytical method was effective enough to quantify low and high concentrations of MJ. The increase of the O/S ME ratio led to a reduction of the droplet diameter. All formulations showed an amorphous structure and the behavior varied between isotropic and anisotropic systems. A decrease in the release of MJ with the increase of the O/S ratio in the formulations was observed. The analytical method developed for the quantitative determination of MJ is suitable to detect and quantify the drug compound from different compositions of MEs in the in vitro release test, and by analogy in other prolonged effects related to the drug reservoir effect of these systems was observed, revealing that ME can be a promising nanocarrier for MJ delivery to tumor cells.
Assuntos
Materiais Biocompatíveis/química , Emulsões/química , Óleos/química , Água/química , Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nanopartículas/química , Tamanho da Partícula , Solubilidade/efeitos dos fármacos , Tensoativos/química , Difração de Raios X/métodosRESUMO
Methotrexate (MTX) is an immunosuppressive drug for systemic use in the treatment of skin diseases, however, MTX presents a number of side effects, such as hepatotoxicity. To overcome this limitation, this study developed skin MTX delivery surfactant systems, such as a microemulsion (ME) and a liquid crystalline system (LCS), consisting of a glycol copolymer-based silicone fluid (SFGC) as oil phase, polyether functional siloxane (PFS) as surfactant, and carbomer homopolymer type A (C971) dispersion at 0.5% (wt/wt) as aqueous phase. Polarized light microscopy and small-angle X-ray scattering evidenced the presence of hexagonal and lamellar LCSs, and also a ME. Texture profile and in vitro bioadhesion assays showed that these formulations are suitable for topical application, showing interesting hardness, adhesiveness and compressibility values. Rheology analysis confirmed the Newtonian behaviour of the ME, whereas lamellar and hexagonal LCSs behave as pseudoplastic and dilatant non-Newtonian fluids, respectively. In vitro release profiles indicated that MTX could be released in a controlled manner from all the systems, and the Weibull model showed the highest adjusted coefficient of determination. Finally, the formulations were not cytotoxic to the immortalized human keratinocyte line HaCaT. Therefore, these bioadhesive surfactant systems established with PFS and C971 have great potential as skin delivery systems.
Assuntos
Metotrexato/farmacologia , Pele/efeitos dos fármacos , Tensoativos/química , Administração Tópica , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Metotrexato/química , Microscopia de Polarização , Reologia , Espalhamento a Baixo Ângulo , SuínosRESUMO
Vulvovaginal candidiasis (VVC) remains a prevalent fungal disease, characterized by challenges, such as increased fungal resistance, side effects of current treatments, and the rising prevalence of non-albicans Candida spp. naturally more resistant. This study aimed to propose a novel therapeutic approach by investigating the antifungal properties and toxicity of 2-hydroxychalcone (2-HC) and 3'-hydroxychalcone (3'-HC), both alone and in combination with fluconazole (FCZ) and clotrimazole (CTZ). A lipid carrier (LC) was also developed to deliver these molecules. The study evaluated in vitro anti-Candida activity against five Candida species and assessed cytotoxicity in the C33-A cell line. The safety and therapeutic efficacy of in vivo were tested using an alternative animal model, Galleria mellonella. The results showed antifungal activity of 2-HC and 3'-HC, ranging from 7.8 to 31.2 as fungistatic and 15.6 to 125.0 mg/L as fungicide effect, with cell viability above 80% from a concentration of 9.3 mg/L (2-HC). Synergistic and partially synergistic interactions of these chalcones with FCZ and CTZ demonstrated significant improvement in antifungal activity, with MIC values ranging from 0.06 to 62.5 mg/L. Some combinations reduced cytotoxicity, achieving 100% cell viability in many interactions. Additionally, two LCs with suitable properties for intravaginal application were developed. These formulations demonstrated promising therapeutic efficacy and low toxicity in Galleria mellonella assays. These results suggest the potential of this approach in developing new therapies for VVC.
RESUMO
The purpose of this study was to evaluate the in vitro anticandidal activity of a methanolic extract of Syngonanthus nitens scapes against different Candida species and clinical isolates from patients with vulvovaginal candidiasis (VVC), and its effect in vivo in the treatment of vaginal infection. Chemical characterization of the extract was performed by HPLC-UV analyses and showed the presence of flavones derivatives. The extract was effective against several Candida strains from our collection and species recovered from VVC patients, and was able to inhibit the yeast-hyphal transition. No cytotoxic activity against human female reproductive tract epithelial cells and no hemolytic activity against human red blood cells were observed. In the in vivo model of VVC, we evaluated the efficacy of the intravaginal treatment with a cream containing the extract at doses of 0.5, 1.0 and 2.0%. The treatment eradicated the vaginal fungal burden in infected rats after 8 days of treatment. S. nitens extract could be considered as an effective and non-toxic natural antifungal agent in the treatment of vulvovaginal candidiasis.
Assuntos
Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Eriocaulaceae/química , Extratos Vegetais/uso terapêutico , Administração Tópica , Animais , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Candida/isolamento & purificação , Candidíase Vulvovaginal/microbiologia , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Flavonas/isolamento & purificação , Flavonas/farmacologia , Flavonas/uso terapêutico , Flavonas/toxicidade , Humanos , Testes de Sensibilidade Microbiana , Pomadas/uso terapêutico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Espectrofotometria Ultravioleta , Resultado do TratamentoRESUMO
The objective of this work was to evaluate the preservative effectiveness of liquid crystalline systems containing retynil palmitate (RP) by the challenge test (CT) and D-value. A system was developed containing water, silicon glycol copolymer, and polyether functional siloxane with 1% RP added. The analyses were carried out by methods in the U.S. Pharmacopeia (USP 31, 2008) using the microorganisms Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger. The CT showed that after 7 days, all microorganisms were eliminated except A. niger, which maintained viability for at least 28 days after inoculation. Moreover, the microorganisms E. coli, P. aeruginosa, S. aureus, C. albicans, and A. niger presented different growth behaviors, evidenced by differences among the D-values calculated. It was concluded that the CT and D-value were efficient methods for evaluation of the preservative property of these formulations.
Assuntos
Cosméticos/química , Conservantes Farmacêuticos , Vitamina A/análogos & derivados , Aspergillus niger/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Diterpenos , Contaminação de Medicamentos/prevenção & controle , Escherichia coli/crescimento & desenvolvimento , Cristais Líquidos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Ésteres de Retinil , Staphylococcus aureus/crescimento & desenvolvimento , Vitamina A/análiseRESUMO
Retinyl palmitate (RP) is widely used as a special interest ingredient in dermatological formulations to improve the elasticity of the skin and to reduce wrinkles by stimulating collagen synthesis. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation into skin and improve the drug action. The effects of such systems on the skin, however, are not completely known. Possible undesirable effects of these formulations on the skin can be detected and interpreted by histopathology and histomorphometry. The objective of this study was to perform a rheological characterization to evaluate the safety of RP used in a lamellar LCS in vitro and in vivo. LCSs containing polyether functional siloxane as a surfactant, silicon glycol copolymer as an oil phase and water at ratios of 60:10:30 and 40:30:30, with (F1v and F2v, respectively) and without (F1 and F2 respectively) RP, were investigated. The rheological characterization was performed using steady shear rate sweep tests and dynamic frequency sweep tests carried out for up to 30 days for various storage temperature conditions (25 ± 2 °C, 37 ± 2 °C and 5 ± 2 °C). Cytotoxic effects were evaluated using J-774 mouse macrophages as a cellular model system. The in vivo tests were conducted on rabbits that had areas of skin treated as follows for 15 days: C (Control); F1; F1v; F2; and F2v. Histomorphometric and histopathological techniques were used to estimate the thicknesses of the epidermis and stratum corneum and the numbers of fibroblasts and leukocytes in the papillary dermis. Mean values were compared by ANOVA, followed by the Tukey test (p < 0.05). The steady shear rate sweep and dynamic frequency sweep tests confirmed the high viscosity of the LCS and the typical pseudo-plastic characteristic of the lamellar system. The RP-unloaded LCS and the RP-loaded LCS did not produce cytotoxicity, nor did they provoke significant thickening of the epidermis and stratum corneum. The number of leukocytes in the treated areas did not change; however, the number of fibroblasts in the area treated with F1v was higher than in the areas treated with the control and F2. The histological analyses demonstrated that none of the formulations irritated the skin and that formulation F1v significantly increased the number of fibroblasts in the dermis, which could result in an increase in the production of collagen.
Assuntos
Cristais Líquidos/química , Reologia , Vitamina A/análogos & derivados , Animais , Contagem de Células , Sobrevivência Celular/efeitos dos fármacos , Diterpenos , Módulo de Elasticidade/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Íons , Camundongos , Coelhos , Ésteres de Retinil , Estresse Mecânico , Vitamina A/farmacologiaRESUMO
Methyl dihydrojasmonate (MJ) has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME) has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S) ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to be nontoxic at doses higher than 350 mg/kg, which was higher than the dose that provides tumor-inhibition effect in this study. Because the MJ-loaded ME was shown to have anticancer activity comparable to doxorubicin, the ME described here may be considered a suitable vehicle for parenteral administration of MJ.
Assuntos
Antineoplásicos , Materiais Biocompatíveis , Ciclopentanos , Portadores de Fármacos , Emulsões , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Ciclopentanos/química , Ciclopentanos/toxicidade , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Emulsões/química , Emulsões/toxicidade , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Microemulsions (MEs) are colloidal systems that can be used for drug-delivery and drug-targeting purposes. These systems are able to incorporate drugs modifying bioavailability and stability and reducing toxic effects. The jasmonate compounds belong to a group of plant stress hormones, and the jasmonic acid and its methyl ester derivative have been described as having anticancer activity. However, these compounds are very poorly water-soluble, not allowing administration by an intravenous route without an efficient nanostructured carrier system. In this work, biocompatible MEs of appropriate diameter size for intravenous route administration, loaded and unloaded with methyl dihydrojasmonate (MJ), were developed and described in a pseudo-ternary phase diagram. The compositions of the MEs were carefully selected from their own regions in the pseudo-ternary phase diagram. The formulations were analyzed by light scattering, polarized light microscopy, and X-ray diffraction. Also, a study on rheological profile was performed. The results showed that the droplet size decreased with both MJ incorporation and oil phase/surfactant ratio. All compositions of the studied MEs showed rheological behavior of pseudoplastic fluid and amorphous structures. In the absence of MJ, most of the studied MEs had thixotropic characteristics, which became antithixotropic in the presence of the drug. Almost all MJ-unloaded MEs presented anisotropic characteristics, but some formulations became isotropic, especially in the presence of MJ. The results of this study support the conclusion that the studied system represents a promising vehicle for in vivo administration of the MJ antitumor drug.
Assuntos
Antineoplásicos/administração & dosagem , Ciclopentanos/administração & dosagem , Sistemas de Liberação de Medicamentos , Materiais Biocompatíveis/química , Química Farmacêutica , Coloides , Emulsões , Humanos , Nanomedicina , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Óleos , Reologia , Solubilidade , ÁguaRESUMO
The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS) with and without retinyl palmitate (RP). LCS containing polyether functional siloxane (PFS) as a surfactant, silicon glycol copolymer (SGC) as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with (OLS(v) = RP-loaded opaque liquid system and TLS(v) = RP-loaded transparent liquid system, respectively) and without (OLS and TLS, respectively) RP were studied. Samples were characterized using polarized light microscopy (PLM) and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging.
Assuntos
Sistemas de Liberação de Medicamentos , Envelhecimento da Pele/efeitos dos fármacos , Vitamina A/análogos & derivados , Administração Tópica , Diterpenos , Avaliação Pré-Clínica de Medicamentos , Humanos , Nanotecnologia , Ésteres de Retinil , Vitamina A/química , Vitamina A/farmacologiaRESUMO
Anionic microemulsions (MEs) containing soya phosphatidylcholine, Tween-20, sodium oleate as surfactant, and cholesterol as oil phase were investigated as drug carriers for amphotericin B. Depending on the composition of the microemulsion, various structures, which differently interact with amphotericin B, can be formed. The nanostructured systems were characterized by photon correlation spectroscopy, rheological behavior, and polarized light microscopy. The results reveal that the droplet diameters increased with amphotericin B incorporation for all ranges of surfactant and oil phase. For both amphotericin B-unloaded and amphotericin B-loaded microemulsions, the profile of the oil droplet diameter decreased with increasing the surfactant concentration, demonstrating the stabilizing effect of the surfactant. The increase in the oil phase proportions led to the growth of the droplet diameter, clearly demonstrating the limit of the surfactant organization in the oil-water interface. The amphotericim B incorporation into microemulsion increased with the fraction volume of the oil phase and the surfactant concentration reaching a plateau at high contents. This profile could be quantitatively analyzed by the framework of the pseudo-phase model that considers the amphotericim B distribution between the oil and the aqueous phases. The rheological analysis showed a pseudoplastic behavior with little thixotropic characteristic. Under polarized light, the system of interest showed a dark background characteristic of dispersed droplets. However, for both amphotericim B-loaded and amphotericim B unloaded microemulsions, the increase in the O/S ratio led to the formation of ordered structures with lamellar arrangements.
Assuntos
Anfotericina B/química , Portadores de Fármacos/química , Emulsões/química , Nanoestruturas/química , Fosfatidilcolinas/química , Colesterol/química , Microscopia , Nanoestruturas/ultraestrutura , Ácido Oleico/química , Tamanho da Partícula , Polissorbatos/química , Reologia , Tensoativos/químicaRESUMO
Thermal analysis has been widely used for obtaining information about drug-polymer interactions and for pre-formulation studies of pharmaceutical dosage forms. In this work, biodegradable microparticles of poly (d,L-lactide-co-glycolide) (PLGA) containing triamcinolone (TR) in various drug:polymer ratios were produced by spray drying. The main purpose of this study was to study the effect of the spray-drying process not only on the drug-polymer interactions but also on the stability of microparticles using differential scanning calorimetry (DSC), thermogravimetry (TG) and derivative thermogravimetry (DTG), X-ray analysis (XRD), and infrared spectroscopy (IR). The evaluation of drug-polymer interactions and the pre-formulation studies were assessed using the DSC, TG and DTG, and IR. The quantitative analysis of drugs entrapped in PLGA microparticles was performed by the HPLC method. The results showed high levels of drug-loading efficiency for all used drug:polymer ratio, and the polymorph used for preparing the microparticles was the form B. The DSC and TG/DTG profiles for drug-loaded microparticles were very similar to those for the physical mixtures of the components. Therefore, a correlation between drug content and the structural and thermal properties of drug-loaded PLGA microparticles was established. These data indicate that the spray-drying technique does not affect the physico-chemical stability of the microparticle components. These results are in agreement with the IR analysis demonstrating that no significant chemical interaction occurs between TR and PLGA in both physical mixtures and microparticles. The results of the X-ray analysis are in agreement with the thermal analysis data showing that the amorphous form of TR prevails over a small fraction of crystalline phase of the drug also present in the TR-loaded microparticles. From the pre-formulation studies, we have found that the spray-drying methodology is an efficient process for obtaining TR-loaded PLGA microparticles.
Assuntos
Anti-Inflamatórios/química , Portadores de Fármacos/química , Microesferas , Temperatura , Triancinolona/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Estabilidade de Medicamentos , Ácido Láctico/química , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Espectrofotometria Infravermelho , Difração de Raios XRESUMO
Microemulsions are transparent, homogeneous and thermodynamically stable systems, formed spontaneously under a specific set of experimental conditions from mixtures of water and oil phases stabilized by a surfactant or a mixture of surfactant and cosurfactant. These systems exhibit some unique properties that make them particularly interesting as delivery systems, as much for the oral as for the topical route. In the present work, we have studied the domain of existence of non-ionic microemulsion systems within pseudo-ternary phase diagrams. The results show a large area of microemulsion domain for O/W and W/O microemulsions. Depending on the proportion of components the apparent viscosity of the systems varied significantly. We have found that the presence of ethanol as cosurfactant affects the physical properties particularly the apparent viscosity and relative density. Analysis of the data indicated that the studied systems behave as non-Newtonian pseudoplastic shear-thinning fluids appropriated for pharmaceutical and cosmetic applications.
Microemulsões são sistemas transparentes, homogêneos e termodinamicamente estáveis, formados espontaneamente, sob determinadas condições experimentais, a partir de misturas de água e fase oleosa estabilizadas por tensoativo ou por mistura de tensoativo e cotensoativo. Esses sistemas exibem propriedades diferenciadas, as quais os tornam particularmente interessantes como sistemas de liberação, principalmente pelas vias oral e tópica. Nesse trabalho foi estudado o domínio da existência de sistemas microemulsionados não iônicos, através de diagramas de fase pseudo-ternários. Os resultados mostraram uma grande área de domínio para microemulsões O/A e A/O, onde A e O referem-se a água e óleo, respectivamente. Dependendo das proporções dos componentes, a viscosidade aparente dos sistemas variou significantemente. Foi determinado que a presença de etanol como cotensoativo modificou as propriedades físico-químicas dos sistemas, particularmente da viscosidade aparente e da densidade relativa. A análise dos dados mostrou que o sistema estudado comporta-se como um fluido não-Newtoniano pseudoplástico próprio para aplicações farmacêuticas e cosméticas.
Assuntos
Emulsões , Fenômenos Químicos , Tensoativos , ViscosidadeRESUMO
Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study, we have analyzed the interaction the sodium diclofenac (SD) with soya phosphaditylcholine (PC) and soya phosphatidylcholine from lyophilized small unilamellar liposomes (SUV). The changes in the properties of the co-lyophilized drug/PC from SUV liposomes, lyophilized PC from SUV liposomes, and lyophilized soya phosphatidylcholine, were studied by Differential Scanning Calorimetry (DSC). The DSC data showed that the previous organization of phospholipids molecules to form liposome affects intensely the thermal behavior of PC when compared to non-lipossomal PC. SD modified the thermal properties of PC from liposomes. It was verified that SD affects intensely the located group peaks in the regions of 120-140 °C and in the higher temperature region of 240-260 °C. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-liposomal PC and that these modifications can be easily monitored by DSC analysis.
Fosfolipídios são freqüentemente usados como compostos anfifílicos estruturais em formulações de lipossomas. Neste estudo foi analisada a interação do diclofenaco sódico (SD) com a fosfatidilcolina de soja liofilizada e a fosfatidilcolina de soja (PC) obtida de lipossomas unilamelares pequenos liofilizados (SUV). As modificações nas propriedades da mistura fármaco/PC co-liofilizados a partir de SUV pré-formados, lipossomas de PC vazios e PC liofilizada foram estudadas por Calorimetria Diferencial de Varredura (DSC). Os resultados de DSC mostraram que a organização prévia das moléculas PC para formar lipossomas interfere significativamente no perfil de DSC da PC, quando comparada ao perfil de DSC da PC não-lipossômica. Verificou-se que o SD afeta intensamente o grupo de picos situados nas regiões de 120-140°C e na região de mais alta temperatura (240-260°C). Os resultados deste trabalho demonstraram que em todos os casos a presença do fármaco modificou o perfil de DSC da PC e que essas modificações podem ser facilmanete monitoradas através da análise de DSC.
Assuntos
Diclofenaco , Lipossomos , Calorimetria/métodos , LiofilizaçãoRESUMO
Lipossomas possuem muitas aplicações farmacêuticas e este manuscrito aborda primariamente o potencial deste sistema coloidal para veiculação de antibióticos e administração através das várias vias de acesso ao organismo. São apresentados inúmeros casos nos quais os lipossomas são usados com sucesso para implementar o efeito antibiótico e evitar efeitos colaterais. Mecanismos envolvidos na liberação intracelular dos fármacos, possibilidades de aplicações, pesquisa e desenvolvimento e esforços para se atingir esses objetivos também são discutidos.(au)
Assuntos
LipossomosRESUMO
Realizou-se a revisäo crítica da literatura a respeito da estabilidade de antibióticos ß-lactâmicos em presença de compostos tensoativos. No desenvolvimento da discussäo, analisaram-se os fatores envolvidos na decomposiçäo dos fármacos. A análise indicou que alguns sistemas organizados, obtidos a partir de tensoativos, podem ser usados no controle de velocidade e em mecanismos de decomposiçäo dos antibióticos. Além disso, esses sistemas podem fornecer informaçöes específicas sobre a reatividade desses fármacos num microambiente similar ao do sítio ativo, onde esses compostos devem exercer seu efeito farmacológico.
Assuntos
Hidrólise , Lactamas/farmacocinética , Micelas , Tensoativos/farmacologiaRESUMO
Este texto relata o estudo da pesquisa relacionada com a aplicaçäo dos lipossomas no controle da liberaçäo e direcionamento de fármacos para doenças bacterianas intracelulares, tais como a tuberculose. Lipossomas possuem muitas aplicaçöes farmacêuticas, e este artigo aborda primariamente o potencial deste sistema coloidal para encapsulaçäo de fármacos, especialmente de compostos antimicobacterianos. Säo apresentados casos nos quais os lipossomas säo usados com sucesso para implementar o efeito antibiótico. Mecanismos envolvidos na liberaçäo intracelular dos fármaco, possibilidades de aplicaçöes, pesquisas e esforços no desenvolvimento para se atingir esses objetivos säo discutidos neste trabalho.
Assuntos
Antibacterianos/uso terapêutico , Biotecnologia , Lipossomos/farmacocinética , Tuberculose , LipossomosRESUMO
A fosfatidilcolina é um fosfolipídeo muito utilizado na obtençäo de lipossomas, o que requer alto grau de pureza. Neste trabalho, foi desenvolvido um método qualitativo e quantitativo de CLAE para a determinaçäo da lecitina de ovo e de soja. O método envolveu coluna de sílica, fase móvel de n-hexano/n-propanol/água e detecçäo por UV em 206 nm. O método apresentou reprodutibilidade apropriada e permitiu a quantificaçäo rápida e segura da fosfatidilcolina.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ovos , Fosfatidilcolinas/análise , Fosfatidilcolinas/biossíntese , Glycine maxRESUMO
Micro e nanocápsulas/esferas säo sistemas modernos e adequados para a administraçäo controlada e seletiva de compostos de uso terapêutico ou para fins de diagnóstico. As evidências experimentais descritas na literatura demonstram o sucesso destes agregados no transporte de grande variedade de fármacos, tais como enzimas, hormônios, antibióticos, anticancerígenos, antifúngicos, antiinflamatórios, analgésicos, entre outros, para administraçäo oral e parenteral. Apresentamos os processos usuais de obtençäo e vários exemplos de aplicaçöes farmacêuticas, assim como säo discutidos alguns problemas da tecnologia destas estruturas