RESUMO
Endometriosis presents high prevalence and its physiopathology involves hyperactivation of endometrial and vaginal cells, especially by bacteria. The disease has no cure and therapies aiming to inhibit its development are highly desirable. Therefore, this study investigated whether MiodesinTM (10 µg/mL = IC80; 200 µg/mL = IC50), a natural compound constituted by Uncaria tomentosa, Endopleura uchi, and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and Candida albicans vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with Candida albicans (1 × 107 to 5 × 107/mL) and LPS (1 µg/mL), respectively. MiodesinTM inhibited mRNA expression for Nuclear factor kappa B (NF-κB), ciclo-oxigenase 1 (COX-1), and phospholipase A2 (PLA2), beyond the C-C motif chemokine ligand 2 (CCL2), CCL3, and CCL5 in VK2 E6/E7 cells (p < 0.05). In addition, the inhibitory effects of both doses of MiodesinTM (10 µg/mL and 200 µg/mL) resulted in reduced secretion of interleukin-1ß (IL-1ß), IL-6, IL-8, tumor necrosis factor α (TNF-α) (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 MiodesinTM inhibited LPS-induced hyperactivation of KLE cells, as demonstrated by reduced secretion of IL-1ß, IL-6, IL-8, TNF-α (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05). Furthermore, MiodesinTM also inhibited mRNA expression and secretion of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor (VEGF), which are key regulators of invasion of endometrial cells. Thus, the study concludes that MiodesinTM presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.
Assuntos
Produtos Biológicos/farmacologia , Endométrio/imunologia , Vagina/imunologia , Candida albicans/fisiologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Endométrio/citologia , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Fosfolipases A2/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , Vagina/citologia , Vagina/microbiologiaRESUMO
Background: Allergic asthma is a chronic lung disease in which the lung inflammation and airway remodeling are orchestrated by both the inflammatory and the immune cells that creates a lung millieu that favors the perpetuation of clinical symptoms. The cell signaling in asthma involves the mast cells activation during initial contact with the allergen and, principally, the participation of eosinophils as well as Th2 cells which determine increased levels of IgE, exaggerated secretion of mucus and collagen, and bronchial hyperreactivity. Moreover, allergic asthma presents lower level of cytokines associated to the both Th1 and Treg cells response, and it implies in deficiency of anti-inflammatory response to counterregulate the exaggerated inflammation against allergen. Therefore, the equilibrium between cytokines as well as transcription factors associated to Th2, Th1, and Treg cells is compromised in allergic asthma. Imuno TF® is a food supplement with ability to interfere in immune system pathways. It has been previously demonstrated that Imuno TF® upregulated Th1 cell response whilst downregulated Th2 cell response in human lymphocytes. Objective: For this reason, we hypothesized that the Imuno TF effect could be restore the balance between Th1/Th2 CD4 T cells response in murine allergic asthma. Methods: Initially, animals were sensitized with OVA via i.p. and challenged with OVA i.n. on days 14, 15 and 16. Treatment with Imuno TF once a day was performed via orogastric from day 17 to day 20. Mice were euthanized on day 21. Results: The Imuno TF reduced eosinophilia, mucus production, and airway remodeling (collagen deposition) in asthma mice. Imuno TF influenced cellular signaling associated to allergic asthma once downregulated STAT6 expression as well as decreased IL-4, IL-5, and IL-13 in lung and serum. In addition, Imuno TF restored T-bet and Foxp3 expression as well as increased IL-12, IFN-É£, and IL-10. Conclusion: Ultimately, Imuno TF mitigated the allergic asthma due to the restoration of balance between the responses of Th1/Th2 as well as Treg cells, and their respective transcription factors the T-bet/STAT6 and Foxp3.
Assuntos
Asma , Pneumonia , Camundongos , Humanos , Animais , Remodelação das Vias Aéreas , Citocinas/metabolismo , Alérgenos , Fatores de Transcrição ForkheadRESUMO
OBJECTIVE: Develop and assess a transdermal emulsion loaded with nanostructured lipid carriers for vitamin D3 supplementation. METHODS: Vitamin D3 loaded nanostructured lipid carriers, produced via high shear homogenization and ultrasonication, were assessed for their particle size, distribution, morphology, zeta potential, entrapment efficiency, and cytotoxicity. They were incorporated into a transdermal vehicle, and the stability and ex vivo permeation were evaluated. RESULTS: Spherical nanoparticles were developed with a particle size of 192.5 nm, a polydispersity index of 0.13, a zeta potential of -29.0 mV, and an entrapment efficiency of 99.75%. They were stable (particle size and distribution) for 15 days when stored in a refrigerator, and for 30 days at room temperature and 32°C. The nanoparticles decreased the drug cytotoxicity against fibroblasts, as shown by IC50 (nanoparticle: 32.48 µg mL-1 vitamin D3: 16.73 µg mL-1). The emulsion loaded with nanoparticles minimized the degradation of vitamin D3 when compared with the nanoparticle dispersion. Additionally, the emulsion provided the skin permeation of vitamin D3 following the recommended daily allowance. CONCLUSION: To the best of our knowledge, this is the first study to use nanostructured lipid carriers for transdermal delivery of vitamin D. The developed formulation is a promising strategy to overcome the vitamin D3 variable oral bioavailability. It also represents a comfortable route of administration; thus it could be beneficial for patients and clinicians. However, further studies are needed to allow the permeation of larger amounts of vitamin D3, and the combination of these nanoparticles with microneedles would be interesting.
Assuntos
Nanopartículas , Nanoestruturas , Administração Cutânea , Colecalciferol/metabolismo , Portadores de Fármacos/metabolismo , Emulsões , Humanos , Lipídeos , Tamanho da Partícula , Pele/metabolismoRESUMO
There are a substantial amount of suppliers for roller mills in the market, but there is a lack of scientific evidence of a roller mill's capacity to improve particle size reduction/distribution or homogenization. In this concise paper, we evaluate the use a roller mill in the final steps of compounding semisolid dosage forms. We performed three simple tests to verify these claims: 1) particle size evaluation through dynamic light scattering and scanning electron microscopy techniques, 2) content uniformity through high-performance liquid chromatography technique, and 3) cross contamination through a cleaning validation method. Dynamic light scattering and scanning electron microscopy techniques of benzoyl peroxide 5% (gel) and testosterone 1% (cream) showed a significant reduction on particle diameter. Content uniformity testing of creams containing progesterone 5%, estradiol 0.1%, and estriol 0.4% showed better homogeneity when using the roller mill. Finally, the proposed cleaning procedure decreased the presence of the compounded preparation to a "none-detection" level after the procedure. This suggests that the roller mill used does, in fact, play a role in the final aspect and quality of pharmaceutical semisolid dosage forms.
Assuntos
Composição de Medicamentos , Estriol , Farmácia , Progesterona/química , Cromatografia Líquida de Alta Pressão , Estriol/química , Tamanho da PartículaRESUMO
Metformin hydrochloride is a traditional, FDA-approved drug used as a first-line drug of choice to treat type 2 diabetes. Research has shown metformin hydrochloride effective in injuries, including age-related maladies. The purpose of this ex vivo study was to evaluate the use of a commercial transdermal vehicle as a semisolid, liposomal vanishing cream (Pentravan) to deliver metformin hydrochloride through the human skin. The experiments were conducted as percutaneous absorption assay in Franz Diffusion Cells, coupled with freshly excised human skin and analyzed by high-performance liquid chromatography. Both methods were based on validated methods of both the United States Pharmacopeial Convention, Inc. and the International Conference on Harmonization. A 46.7% permeation percentage was found, with a drug flux of 3.91 µg cm-2 h-1 and a lag time of 0.51 h, following pseudo first-order absorption kinetics. These results showed that transdermal metformin hydrochloride can be an option for patients searching for diverse clinical effects.
Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Absorção Cutânea/fisiologia , Administração Cutânea , Humanos , Metformina/administração & dosagem , PeleRESUMO
BACKGROUND: Transdermal delivery is an alternative route for the administration of drugs. However, it requires the development of vehicles that allow the drugs to cross the layers of the skin and reach the systemic circulation. OBJECTIVE: In this study, a new transdermal vehicle was evaluated using progesterone, estradiol, estradiol + estriol (Biest) and ketoprofen administered as model drugs. METHODS: To evaluate the ex vivo permeation of the drugs, the Franz vertical diffusion cell with human skin was used. RESULTS: After 24 h, the vehicle was able to deliver 18.32 µg/cm2 of progesterone and 92.07 µg/cm2 of ketoprofen through the skin to the receptor medium. The permeation percentages were 91%, 78.8%, 48.5%, 73.2%, and 63.6%, respectively, for estradiol, estradiol (Biest), estriol (Biest), progesterone and ketoprofen. For all drugs, sufficient amounts were delivered to achieve a systemic effect, and it was also possible to decrease the amount of emulsion applied. CONCLUSION: Thus, the vehicle demonstrated a high performance and the possibility of it being used for drugs that present difficulties in regards to administration by the transdermal route.
Assuntos
Sistemas de Liberação de Medicamentos , Absorção Cutânea , Pele/metabolismo , Administração Cutânea , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Combinação de Medicamentos , Estradiol/administração & dosagem , Estriol/administração & dosagem , Feminino , Humanos , Técnicas In Vitro , Cetoprofeno/administração & dosagem , Progesterona/administração & dosagemRESUMO
Halitosis can be described as unpleasant odors emanating from the oral cavity. It is usually associated with decomposition action of bacteria present mainly on the back of the tongue and periodontal pockets, and able to produce volatile sulfur compounds. We conducted a study at the Faculty of Dentistry, Federal University of Juiz de Fora and evaluated the therapeutic effect of two natural extracts, Camellia sinensis (green tea) and resveratrol in the form of oral polymer films, to control halitosis. Fifty volunteers (students of health courses) participated in the research after orientation and signing the informed consent form. The anamnesis was made by researchers. The physical examination was made to verify the inclusion criteria. Each participant received 45 polymeric films to be consumed in 15 days (3 films per day). Measurements of the volatile sulfur compound levels were performed using a halimeter in two stages: 1) before use and 2) 15 days after the first administration. Results showed a statistically significant reduction in volatile sulfur compound levels in 71.79% of the volunteers. We concluded that the compounded orodispersible films containing green tea and resveratrol demonstrated excellent results in reducing halitosis.
Assuntos
Camellia sinensis , Portadores de Fármacos , Halitose/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polímeros/química , Resveratrol/administração & dosagem , Administração Oral , Adulto , Brasil , Camellia sinensis/química , Formas de Dosagem , Esquema de Medicação , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Halitose/diagnóstico , Humanos , Masculino , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Resveratrol/química , Solubilidade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Compounded liquid medication is frequently required in children to allow easy dose adjustment and overcome swallowing difficulties. The objective of this study was to evaluate the stability of oral suspensions compounded with SyrSpend SF PH4 and the commonly used active pharmaceutical ingredients baclofen 2.0 mg/mL, carvedilol 5.0 mg/mL, hydrochlorothiazide 2.0 mg/mL, mercaptopurine 10.0 mg/mL, methadone hydrochloride 10.0 mg/mL, oseltamivir phosphate 6.0 mg/mL, phenobarbital 9.0 mg/mL and 15.0 mg/mL, propranolol hydrochloride 0.5 mg/mL and 5.0 mg/mL, pyrazinamide 100.0 mg/mL, spironolactone 2.0 mg/mL and 2.5 mg/mL, sotalol hydrochloride 5.0 mg/mL, tacrolimus monohydrate 0.5 mg/mL, ursodeoxycholic acid 20.0 mg/mL, and vancomycin hydrochloride 25.0 mg/mL. Suspensions were compounded with raw powders, except for mercaptopurine, pyrazinamide, and sotalol hydrochloride, which were made from commercial tablets. Stability was assessed by measuring the percentage recovery at 0 (baseline), 60 days, and 90 days after compounding for suspensions made with raw powders, which were stored at 2ÅãC to 8ÅãC. The stability of tablets, which were stored at 2ÅãC to 8ÅãC and 20ÅãC to 25ÅãC, was assessed by measuring the percentage recovery at 0 (baseline), 7 days, 14 days, 30 days, 60 days, and 90 days. Active pharmaceutical ingredients quantification was performed by ultraviolet high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions in the conditions tested. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.
Assuntos
Baclofeno/química , Carvedilol/química , Hidroclorotiazida/química , Mercaptopurina/química , Metadona/química , Oseltamivir/química , Veículos Farmacêuticos/química , Fenobarbital/química , Propranolol/química , Sotalol/química , Espironolactona/química , Amido/química , Tacrolimo/química , Ácido Ursodesoxicólico/química , Vancomicina/química , Administração Oral , Baclofeno/administração & dosagem , Carvedilol/administração & dosagem , Composição de Medicamentos , Estabilidade de Medicamentos , Hidroclorotiazida/administração & dosagem , Concentração de Íons de Hidrogênio , Mercaptopurina/administração & dosagem , Metadona/administração & dosagem , Oseltamivir/administração & dosagem , Soluções Farmacêuticas , Fenobarbital/administração & dosagem , Propranolol/administração & dosagem , Pirazinamida/administração & dosagem , Sotalol/administração & dosagem , Espironolactona/administração & dosagem , Suspensões , Tacrolimo/administração & dosagem , Temperatura , Fatores de Tempo , Ácido Ursodesoxicólico/administração & dosagem , Vancomicina/administração & dosagemRESUMO
BACKGROUND: Taxifolin (TAX) is a flavonoid that has numerous pharmacological properties, including an antioxidant ability superior to that of other flavonoids due to its particular structure. Nevertheless, it has low oral bioavailability, which limits its therapeutic application. In this context, potentially important approaches for systemic drug delivery could be by alternative routes such as skin and vaginal mucosa, once both routes have a variety of advantages compared with the oral route, including the ability to bypass both first-pass hepatic metabolism and the consequent degradation in the gastrointestinal tract. Vaginal delivery could also account for a local effect, or an effect on circumvent microregion. OBJECTIVE: The major objective of this study was to develop and validate a high-performance liquid chromatography (HPLC) method for the determination of TAX in a semisolid dosage forms and then to evaluate ex vivo permeations across porcine vaginal mucosa and human skin. METHODS: TAX was incorporated into an oil-in-water emulsion developed previously by our group. Method for quantification was developed and validated using HPLC. Permeation through human skin and vaginal porcine mucosa were conducted in Franz-type cells. RESULTS: The method was precise (CV < 5%), accurate (recovery between 98% and 102%), linear (R2> 0.99), specific, and robust. Permeation experiments through porcine vaginal mucosa and human skin presented permeated percentages equal to 87.43% and 48.09% (per dose), respectively. CONCLUSION: The results suggest that, in the matrixes studied, TAX may be able to exert its biological activities systemically when applied by these routes. Furthermore, it exhibits greater permeability potential when administered by intravaginal route.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Mucosa/metabolismo , Quercetina/análogos & derivados , Creme para a Pele/administração & dosagem , Pele/metabolismo , Administração Tópica , Adulto , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Emulsões , Feminino , Humanos , Técnicas In Vitro , Permeabilidade , Quercetina/administração & dosagem , Quercetina/farmacocinética , Absorção Cutânea , Creme para a Pele/farmacocinética , Suínos , VaginaRESUMO
OBJECTIVES: To evaluate the microbiological and physicochemical compatibility of commonly used proton pump inhibitors (PPIs) esomeprazole, lansoprazole, omeprazole and pantoprazole compounded at a single concentration using SyrSpend SF Alka and stored at refrigerated temperatures (omeprazole was also stored at room temperature because it has the most widespread use). METHODS: Compatibility was assessed by measuring the per cent recovery at varying time points throughout a 90-day period. Quantification of the APIs was performed by a validated high performance liquid chromatography (HPLC-UV) method. This same assay was also used to determine the dosage content uniformity of the suspensions. Microbiological stability ('test in use') was assessed during 60â days and total aerobic microbial count (TAMC), total combined yeasts and moulds count (TYMC), detection of Escherichia coli and pH determination were performed. Antimicrobial effectiveness testing was determined following European Pharmacopoeia guidelines. RESULTS: Beyond-use dates of maximum 60â days for omeprazole (5â mg/mL), pantoprazole (3â mg/mL) and esomeprazole (3â mg/mL) were established. All suspensions that met the physicochemical criteria for stability also met the content uniformity criteria. The suspensions showed no antimicrobial efficiency against bacteria, yeasts and moulds as SyrSpend SF Alka is an unpreserved vehicle, but the 'test in use' showed that the suspensions can remain microbiologically stable for up to 60â days. CONCLUSIONS: SyrSpend SF Alka can be used to compound palatable (taste-masking properties) preservative-free oral suspensions with almost all commonly used PPIs.