RESUMO
To increase the skin permeation of pranoprofen from the ethylene-vinyl acetate (EVA) matrix, different types of enhancers were added to an EVA matrix containing 2% pranoprofen. The pharmacokinetics and bioavailability of pranoprofen, an anti-inflammatory drug, were examined to determine the feasibility of an enhanced transdermal delivery system for pranoprofen from an EVA matrix containing caprylic acid as the enhancer in rats. The effects of the enhancers on the level of pranoprofen permeation through the skin were evaluated using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, including the fatty acids (saturated, unsaturated), the glycols, the glycerides, and the pyrrolidones, caprylic acid showed the best enhancement. A pranoprofen-EVA matrix system was formulated containing caprylic acid as an enhancer. The pranoprofen-EVA matrix system (8 mg/kg) was applied to the abdominal skin of rats. The blood samples were collected through the femoral artery for 24 h and the plasma concentrations of pranoprofen were determined by HPLC. The pharmacokinetic parameters were calculated using the MULTI computer program. The area under the curve (AUC) was significantly higher in the enhancer group (55.49 +/- 13.87 ng/mL.h) than in the control group (22.48 +/- 5.63 ng/mL.h), which was treated transdermally without the enhancer, showing about 246% increased bioavailability (p<0.05). As the pranoprofen-EVA matrix containing caprylic acid as an enhancer was administered to rats via the transdermal routes, the relative bioavailability increased about 2.46-fold compared to the control group, showing a relatively constant, sustained blood concentration. These results show that a pranoprofen-EVA matrix containing a permeation enhancer could be developed as a transdermal delivery system to provide a sustained plasma concentration.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Benzopiranos/farmacocinética , Caprilatos/farmacologia , Portadores de Fármacos , Polivinil/química , Propionatos/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/química , Área Sob a Curva , Benzopiranos/administração & dosagem , Benzopiranos/sangue , Benzopiranos/química , Disponibilidade Biológica , Caprilatos/administração & dosagem , Caprilatos/química , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estudos de Viabilidade , Masculino , Modelos Biológicos , Permeabilidade , Propionatos/administração & dosagem , Propionatos/sangue , Propionatos/química , Ratos , Ratos Sprague-DawleyRESUMO
Pyrrolidine dithiocarbamate (PDTC), an antioxidant with a metal-chelating activity, has been used widely to inhibit the expression of inflammatory genes in vitro and in vivo. This study investigated whether PDTC has an antimicrobial activity against various bacteria. The antibacterial activity of PDTC and other compounds was evaluated in vitro by the broth microdilution method against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Staphylococcus aureus, and Escherichia coli. Bacterial growth was inhibited by PDTC, where a wide range of sensitivity was demonstrated among the tested bacteria. The antibacterial activity of PDTC was reduced by the addition of copper chloride; in contrast, it was enhanced considerably by zinc chloride. Two different zinc chelators, Ca-saturated EDTA (Ca-EDTA) and N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine, blocked the antibacterial activity of PDTC, whereas Zn-EDTA failed to reduce the activity of PDTC. These results demonstrate for the first time that PDTC possesses an antibacterial activity, for which zinc is required, and suggest that PDTC, possessing a dual anti-inflammatory and antibacterial activity, may be considered for topical use for inflammatory diseases of bacterial origin.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Quelantes/farmacocinética , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Bactérias/metabolismo , Cloretos/metabolismo , Cobre/metabolismo , Compostos de Zinco/metabolismoRESUMO
Sodium fluoride (NaF) has been shown to be cytotoxic and produces inflammatory responses in humans. However, the cellular mechanisms underlying the NaF-induced cytotoxicity in periodontal tissues are unclear. This study examined whether or not NaF induces apoptosis in human gingival fibroblasts (HGF), and its underlying mechanisms by monitoring various apoptosis-associated processes. NaF reduced the cell viability of HGF in a dose- and time-dependent manner. NaF increased TUNEL-positive cell and induced apoptosis with concomitant chromatin condensation and DNA fragmentation in HGF. In addition, NaF increased the level of cytochrome c released from the mitochondria into the cytosol, enhanced the caspase-9, -8 and -3 activities, the cleavage of poly (ADP-ribose) polymerase (PARP), and up-regulated the voltage-dependent anion channel (VDAC) 1. However, NaF did not affect the production of reactive oxygen species (ROS) which is a strong apoptotic inducer. Furthermore, NaF up-regulated the Fas-ligand (Fas-L), a ligand of death receptor. Bcl-2, a member of the anti-apoptotic Bcl-2 family, was down-regulated, whereas the expression of Bax, a member of the pro-apoptotic Bcl-2 family, was unaffected in the NaF-treated HGF. These results suggest that NaF induces apoptosis in HGF through both the mitochondria-mediated pathways regulated by the Bcl-2 family and death receptor-mediated pathway.
Assuntos
Apoptose/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Morte Celular/metabolismo , Fluoreto de Sódio/farmacologia , Western Blotting , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatina/efeitos dos fármacos , Cromatina/metabolismo , Citocromos c/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Gengiva/citologia , Humanos , Mitocôndrias/metabolismo , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
The aim of this study was to determine if a ketorolac tromethamine (KT) gel solution could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic and anti-inflammatory effects in a rat carrageenan inflammation model. 1% carrageenan was injected into the plantar surface of the right hindpaw of a rat, and anti-hyperalgesic and anti-inflammatory effects of KT via phonophoretic transdermal delivery were examined. The changes in the mechanical and thermal hyperalgesia, nociceptive flexor reflex (NFR), as well as the swelling changes were determined. According to the anti-hyperagesia and anti-inflammation tests, which were used to determine the change in the pain threshold, NFR and swelling showed that the group given the phonophoretic transdermal delivery of KT exhibited significantly more noticeable anti-hyperalgesic and anti-inflammatory effects than those treated with the simple application of a KT gel. The transdermal application of KT gel using phonophoresis had significant anti-hyperalgesic and anti-inflammatory effects. These findings suggest that the transdermal administration of a KT gel using phonophoresis using pulsed ultrasound might be useful for treating acute inflammation and pain.
Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Edema/prevenção & controle , Hiperalgesia/prevenção & controle , Cetorolaco de Trometamina/administração & dosagem , Limiar da Dor/efeitos dos fármacos , Fonoforese , Administração Cutânea , Animais , Carragenina , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/fisiopatologia , Géis , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Masculino , Medição da Dor , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Fatores de TempoRESUMO
Epigallocatechin-3-gallate (EGCG) is a major constituent of green tea polyphenols. This study was aimed to investigate the possible mechanisms of EGCG-mediated inhibition against apoptosis in rat pheochromocytoma PC12 cells by exposure to CoCl(2). Exposure to CoCl(2) caused the generation of ROS and induced cell death with appearance of apoptotic morphology and DNA fragmentation. However, EGCG rescued the loss of viability in the cells exposed to CoCl(2) and led the reduction of DNA fragmentation and sub-G(1) fraction of cell cycle. Also, EGCG attenuated the CoCl(2)-induced disruption of mitochondrial membrane potential (DeltaPsim), release of cytochrome c from the mitochondria to cytosol and abolished the CoCl(2)-stimulated activities of the caspase cascades, caspase-9 and caspase-3. In addition, EGCG ameliorated the increase in the Bax to Bcl-2 ratio, a marker of apoptosis proceeding, induced by CoCl(2) treatment. Taken together, the present results suggest that EGCG inhibit the CoCl(2)-induced apoptosis of PC12 cells through the mitochondria-mediated apoptosis pathway involved in modulating the Bcl-2 family.
Assuntos
Apoptose/efeitos dos fármacos , Catequina/análogos & derivados , Cobalto/antagonistas & inibidores , Cobalto/toxicidade , Fármacos Neuroprotetores/farmacologia , Animais , Western Blotting , Caspase 3/metabolismo , Caspase 9/metabolismo , Catequina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Eletroforese em Gel de Ágar , Citometria de Fluxo , Genes bcl-2/genética , Hipóxia-Isquemia Encefálica/patologia , Potenciais da Membrana/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sais de Tetrazólio , TiazóisRESUMO
Ketorolac tromethamine gel (KT gel) and ketorolac tromethamine gel containing genipin (KTG gel) were prepared and their therapeutic effects on periodontitis were evaluated. The skin permeation rate of ketorolac from the KT gel and KTG gel was 5.75+/-0.53 and 5.82 +/- 0.74 microg/cm2/ h, respectively. The skin permeation rate of genipin from the KTG gel was 10.13 +/- 1.47 microg/ cm2/h. The tensile strength of the KTG gel was larger than the KT gel. After 4 weeks, the periodontal pocket depth of the KTG gel group (3.22 +/- 0.20 mm) significantly decreased compared with the non-treated group (4.50 +/- 0.25 mm) and the KT group (3.84 +/- 00.26 mm). The KTG gel did not induce separation of the stratum corneum and subcutaneous tissue, and the collagen layers of the corium were closer, more fibrous, and showed longer connections than in the other groups. The KTG gel appears to be effective against gingivitis in the periodontal pocket through its increased anti-inflammatory activity and the crosslinking of genipin with the biological tissue.
Assuntos
Iridoides/uso terapêutico , Cetorolaco de Trometamina/uso terapêutico , Doenças Periodontais/tratamento farmacológico , Adesivos Teciduais/uso terapêutico , Adulto , Animais , Cromatografia Líquida de Alta Pressão , Método Duplo-Cego , Combinação de Medicamentos , Composição de Medicamentos , Feminino , Géis , Humanos , Técnicas In Vitro , Glicosídeos Iridoides , Iridoides/administração & dosagem , Iridoides/química , Iridoides/farmacocinética , Cetorolaco de Trometamina/administração & dosagem , Cetorolaco de Trometamina/química , Cetorolaco de Trometamina/farmacocinética , Masculino , Camundongos , Camundongos Pelados , Pessoa de Meia-Idade , Doenças Periodontais/metabolismo , Absorção Cutânea/efeitos dos fármacos , Resistência à Tração , Adesivos Teciduais/administração & dosagem , Adesivos Teciduais/química , Adesivos Teciduais/farmacocinéticaRESUMO
To develop the new gel formulations that show sustained release for a period of time, the bioadhesive carbopol gels containing tretinoin were prepared. The release characteristics of drug from the carbopol gel were studied according to temperature, receptor medium and drug concentration. For the enhancement of its percutaneous absorption, some kinds of penetration enhancer were used. As the concentration of drug increased, the release of drug from the gel increased, showing concentration dependency. The increase of temperature showed the increased drug release, depending on the activation energy of permeation. Among the enhancers used such as the glycols and the non-ionic surfactants, polyoxyethylene 2-oleyl ether showed the best enhancing effect. The carbopol gels of tretinoin containing an enhancer could be developed for the enhanced transdermal delivery of drug.
Assuntos
Ceratolíticos/administração & dosagem , Ceratolíticos/farmacocinética , Tretinoína/administração & dosagem , Tretinoína/farmacocinética , Resinas Acrílicas , Administração Cutânea , Algoritmos , Animais , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Difusão , Géis , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Masculino , Polivinil , Ratos , Ratos Sprague-Dawley , TemperaturaRESUMO
In relieving local pains, lidocaine, one of ester type local anesthetics, has been used. To develop the lidocaine gels of enhanced local anesthetic effects, hydroxypropyl methylcellulose (HPMC) based bioadhesive polymer gel containing an enhancer was formulated. As the drug concentration in the gels increased up to 3%, the permeation rate of drug linearly increased, thereafter reaching a plateau. As the temperature of surrounding solutions increased, the permeation of drug increased. The activation energy of drug permeation was 3.29 kcal/mol for lidocaine. The permeation rate of drug through skin was studied using various enhancers, such as glycols, non-ionic surfactants, and bile salts. Among the enhancers studied, diethylene glycol showed the greatest enhancing effects on drug permeation through skin. The analgesic activity was examined using a tail-flick analgesimeter. In the area under the efficacy curve (AUEC) of the rat-tail flick tests, lidocaine gel containing diethylene glycol showed about 3.89-fold increase in analgesic activity compared with the control. The addition of vasoconstrictor in the gels prolonged the analgesic effects. The result of this study supports that the bioadhesive gel with efficient anesthetic effect could be developed using HPMC with combination of enhancer and vasoconstrictor.
Assuntos
Anestésicos Locais/administração & dosagem , Lidocaína/administração & dosagem , Metilcelulose/análogos & derivados , Animais , Géis , Derivados da Hipromelose , Lidocaína/farmacologia , Masculino , Metilcelulose/administração & dosagem , Camundongos , Camundongos Endogâmicos ICR , Absorção Cutânea , TemperaturaRESUMO
This study was performed to develop new enhanced anesthetic benzocaine gels with a suitable bioadhesive property for local anesthetic effects. As the concentration of benzocaine in the HPMC gels increased up to 15%, the permeation of drug increased, thereafter slightly increased. The activation energy of drug permeation was 11.29 kcal/mol. Bioadhesive forces were also measured. The permeation rate of drug through the skin was studied using various enhancers, such as glycols, non-ionic surfactants or fatty acids. Among the enhancers used, diethylene glycol showed the most enhancing effects. Analgesic activity was examined using a tail-flick analgesimeter. According to the rat tail-flick test, the value of AUEC (0 - 360min) of 15% benzocaine gels containing diethylene glycol was 4662 +/- 200 s min, while that of gels without diethylene glycol was 3353 +/- 132 s min, showing about 1.39-fold increase in analgesic activity. Fifteen percentage of benzocaine gels containing diethylene glycol showed the most enhanced, prolonged analgesic effects, showing the maximum anesthetic effects at 240 min, while the gels without diethylene glycol showed maximum effect at 180 min.
Assuntos
Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Benzocaína/administração & dosagem , Benzocaína/farmacologia , Metilcelulose/análogos & derivados , Adesividade , Adjuvantes Farmacêuticos/farmacologia , Administração Cutânea , Anestésicos Locais/farmacocinética , Animais , Benzocaína/farmacocinética , Ácidos Graxos/farmacologia , Géis , Glicóis/farmacologia , Derivados da Hipromelose , Técnicas In Vitro , Metilcelulose/química , Peso Molecular , Permeabilidade , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Tensoativos/farmacologia , TemperaturaRESUMO
Opinions vary as to what extent handicapped children differ in oral health from children without handicapping conditions. The present study was a comprehensive study and evaluation of oral health comparing 267 handicapped and 128 nonhandicapped persons with regard to caries rate, occlusion, and periodontal condition. The dft, dfs, and DMFT indices of handicapped according to age were significantly lower than those of nonhandicapped subjects. The prevalence of gingivitis in handicapped persons increased with age and was significantly higher than that reported for nonhandicapped subjects. The handicapped group had a significantly higher percentage of Class II and Class III occlusion than that observed in the comparison group.
Assuntos
Cárie Dentária/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , Gengivite/epidemiologia , Má Oclusão/epidemiologia , Adolescente , Adulto , Fatores Etários , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Índice CPO , Crianças com Deficiência/estatística & dados numéricos , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Má Oclusão/classificação , Índice Periodontal , PrevalênciaRESUMO
The interaction between Lactobacillus reuteri, a probiotic bacterium, and oral pathogenic bacteria have not been studied adequately. This study examined the effects of L. reuteri on the proliferation of periodontopathic bacteria including Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia, and on the formation of Streptococcus mutans biofilms. Human-derived L. reuteri strains (KCTC 3594 and KCTC 3678) and rat-derived L. reuteri KCTC 3679 were used. All strains exhibited significant inhibitory effects on the growth of periodontopathic bacteria and the formation of S. mutans biofilms. These antibacterial activities of L. reuteri were attributed to the production of organic acids, hydrogen peroxide, and a bacteriocin-like compound. Reuterin, an antimicrobial factor, was produced only by L. reuteri KCTC 3594. In addition, L. reuteri inhibited the production of methyl mercaptan by F. nucleatum and P. gingivalis. Overall, these results suggest that L. reuteri may be useful as a probiotic agent for improving oral health.
Assuntos
Antibiose , Limosilactobacillus reuteri/fisiologia , Boca/microbiologia , Animais , Antibacterianos/metabolismo , Bacteroidetes/crescimento & desenvolvimento , Fusobacterium nucleatum/crescimento & desenvolvimento , Humanos , Limosilactobacillus reuteri/metabolismo , Pasteurellaceae/crescimento & desenvolvimento , Porphyromonas gingivalis/crescimento & desenvolvimento , Ratos , Streptococcus mutans/crescimento & desenvolvimentoRESUMO
Interactions between periodontal bacteria and human oral epithelial cells can lead to the activation and expression of a variety of inflammatory mediators in epithelial cells. Fusobacterium nucleatum is a filamentous human pathogen that is strongly associated with periodontal diseases. This study examined the effects of methyl gallate (MG) and gallic acid (GA) on the production of inflammatory mediators, interleukin (IL)-6 and IL-8, by oral epithelial cells stimulated by F. nucleatum. In a real-time reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, live F. nucleatum induced high levels of gene expression and protein release of IL-6 and IL-8. The effects of MG and GA were examined by treating KB oral epithelial cells with MG and GA and stimulating them with F. nucleatum. MG and GA inhibited significantly the increases in the IL-6 and IL-8 gene and protein levels in a dose-dependent manner. These Compounds also inhibited the growth of F. nucleatum. No visible effects of MG and GA on the adhesion and invasion of KB cells by F. nucleatum were observed. In conclusion, both MG and GA inhibit IL-6 and IL-8 production from F. nucleatum-activated KB cells.
Assuntos
Células Epiteliais/microbiologia , Fusobacterium nucleatum/imunologia , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacologia , Fatores Imunológicos/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/imunologia , Perfilação da Expressão Gênica , Humanos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
An ethylene-vinyl acetate (EVA) matrix containing plasticizer was prepared as a potential controlled release system for loratadine. The EVA matrix containing loratadine was prepared as the transdermal device using casting methods. The solubility of loratadine according to the volume fraction of PEG 400 was determined. The effects of the drug concentration, temperature, and plasticizers on the release of the drug were determined at 37 degrees C using 40% PEG 400 solution as the receptor medium using the modified Keshary-Chien cell. Some types of plasticizers. such as citrates and phthalates, were used to prepare the pores and increase the flexibility of the EVA matrix. The solubility test according to the PEG 400 volume fraction revealed the highest solubility in the 40% PEG 400 solution. The rate of drug released from the EVA matrix increased with increasing temperature and drug loading. There was a linear relationship between the release rate and the square root of the loading dose. The activation energy for drug release from the EVA matrix with a loading dose of 1%, 2%, 3%, 4%, and 5% was estimated to be 6.83, 6.80, 6.77, 6.71, and 6.65 kcal/mol, respectively Among the plasticizers used, diethyl phthalate showed the highest level of loratadine release. In conclusion, an EVA matrix containing plasticizer could be used to enhance the controlled release of loratadine.
Assuntos
Excipientes/química , Antagonistas não Sedativos dos Receptores H1 da Histamina/química , Loratadina/química , Plastificantes/química , Polivinil/química , Administração Cutânea , Cromatografia Líquida de Alta Pressão , Citratos/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Cinética , Membranas Artificiais , Permeabilidade , Ácidos Ftálicos/química , Polietilenoglicóis/química , Solubilidade , TemperaturaRESUMO
Porphyromonas gingivalis is one of the suspected periodontopathic bacteria. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Inflammatory cytokines play important roles in the gingival tissue destruction that is a characteristic of periodontitis. Macrophages are prominent at chronic inflammatory sites and are considered to contribute to the pathogenesis of periodontitis. Xylitol stands out and is widely believed to possess anticaries properties. However, to date, little is known about the effect of xylitol on periodontitis. The aim of the present study was to determine tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) expression when RAW 264.7 cells were stimulated with P. gingivalis LPS (hereafter, LPS refers to P. gingivalis LPS unless stated otherwise) and the effect of xylitol on the LPS-induced TNF-alpha and IL-1beta expression. The kinetics of TNF-alpha and IL-1beta levels in culture supernatant after LPS treatment showed peak values at 1 h (TNF-alpha) and 2 to 4 h (IL-1beta), respectively. NF-kappaB, a transcription factor, was also activated by LPS treatment. These cytokine expressions and NF-kappaB activation were suppressed by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB). Pretreatment with xylitol inhibited LPS-induced TNF-alpha and IL-1beta gene expression and protein synthesis. LPS-induced mobilization of NF-kappaB was also inhibited by pretreatment with xylitol in a dose-dependent manner. Xylitol also showed inhibitory effect on the growth of P. gingivalis. Taken together, these findings suggest that xylitol may have good clinical effect not only for caries but also for periodontitis by its inhibitory effect on the LPS-induced inflammatory cytokine expression.