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PURPOSE: Evaluate and compare the retention time on the canine ocular surface of crosslinked hyaluronic acid (X-HA), linear hyaluronic acid (L-HA) and saline solution using fluorescent compounds (fluorescein sodium salt, Alexa Fluor 488 cadaverine and Alexa Fluor 488 maleimide). METHODS: 0.9% saline solution (SAL) was combined with fluorescein sodium salt. X-HA and L-HA were covalently modified using Alexa Fluor 488 reactive moieties. Eye drops were applied to 70 eyes of 35 dogs that were previously assessed and determined to have a normal ocular surface. Employing a blue light filter (450-490 nm), digital images were captured from instillation to 180 min. Images were analyzed to assess the percent of the total ocular area covered with green fluorescence at various time points. RESULTS: X-HA exhibited a dual phase behavior: A broad microgel coverage first, followed by accumulation in tear film meniscus and medial canthus in the second phase, remaining in contact with the ocular surface up to 180 min. Coverage with L-HA and SAL eye drops quickly migrated to the tear meniscus. No traces of the fluorescent compounds were observed by 45 min in eyes treated with SAL solution compound and, by 120 min, eyes treated with L-HA. CONCLUSIONS: X-HA exhibited a significantly increased ocular surface contact time with the ocular surface compared with L-HA and SAL. Not only could this indicate extended lubrication time but also supports the potential use of this compound as a method for topical sustained-release drug application.
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Fluorofotometría , Ácido Hialurónico , Soluciones Oftálmicas , Animales , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/química , Perros , Soluciones Oftálmicas/química , Fluorofotometría/veterinaria , Fluorofotometría/métodos , Ojo/efectos de los fármacos , Masculino , FemeninoRESUMEN
OBJECTIVE: The aim of this study was to analyze possible alterations (morphological and inflammatory) in the ocular cells of fetuses from mothers with insulin resistance exposed to saturated fatty acids through the period of pregnancy. METHODS: Wistar female rats were induced to develop insulin resistance before pregnancy. Fetuses' skulls were collected on the 20th day of intrauterine life. The rats were separated on the first day of management into two groups according to the diet applied: control group (C): diet containing soybean oil as a source of fat; and saturated fatty acid group (S): diet containing butter as a source of fat. RESULTS: Histological and immunohistochemical analyses have been conducted. The immunohistochemical analyses of interleukin 6, suppressor of cytokine signaling, 3 and signal transducer and activator of transcription 3 did not demonstrate alterations in the expression of proteins in the fetuses of mothers fed with a saturated fatty diet. Moreover, no histopathological changes were noticed between groups. CONCLUSION: The saturated fatty diet does not induce tissue changes or activate the Janus kinase/signal transducer and activator of transcription signaling pathway during eye development in the fetuses of mothers with insulin resistance.
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Resistencia a la Insulina , Quinasas Janus , Ratas Wistar , Transducción de Señal , Animales , Femenino , Embarazo , Transducción de Señal/efectos de los fármacos , Resistencia a la Insulina/fisiología , Quinasas Janus/metabolismo , Ácidos Grasos/análisis , Grasas de la Dieta/farmacología , Grasas de la Dieta/efectos adversos , Feto/efectos de los fármacos , Inmunohistoquímica , Factor de Transcripción STAT3/metabolismo , Interleucina-6/análisis , Interleucina-6/metabolismo , Ratas , Ojo/embriología , Ojo/efectos de los fármacosRESUMEN
The TRPV1 receptor, which is known to contribute significantly to pain perception, has recently been identified as a useful tool for predicting eye stinging potential in cosmetics. In this study, HEK-293 cells with high TRPV1 expression were utilized to evaluate calcium influx related to receptor activation triggered by chemicals and cosmetic formulations. The cells were exposed to increasing concentrations of substances to cause or not some aggression to the eye, and TRPV1 activity was assessed by measuring intracellular FURA-2 AM fluorescence signal. To confirm TRPV1 channel activation, capsazepine, a capsaicin antagonist, was employed in addition to using capsaicin as a positive control. The study's results indicate that this novel model can identify compounds known to cause some aggression to the eye, such as stinging, considering a cut-off value of 60% of Ca2+ influx exposed to the lowest evaluated concentration (0.00032%). When applied to the cosmetic baby formulation, although the presented model exhibited higher sensitivity by classifying as stinging formulations that had previously undergone clinical testing and were deemed non-stinging, the assay could serve as a valuable in vitro tool for predicting human eye stinging sensation and can be used as a tier 1 in an integrated testing strategy.
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Calcio , Cosméticos , Canales Catiónicos TRPV , Humanos , Cosméticos/toxicidad , Células HEK293 , Canales Catiónicos TRPV/metabolismo , Calcio/metabolismo , Ojo/efectos de los fármacos , Capsaicina/análogos & derivados , Capsaicina/farmacología , Alternativas a las Pruebas en AnimalesRESUMEN
Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.
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Anexina A1/uso terapéutico , Antiinflamatorios/uso terapéutico , Dioxolanos/uso terapéutico , Péptidos/uso terapéutico , Uveítis/inducido químicamente , Uveítis/tratamiento farmacológico , Animales , Anexina A1/administración & dosificación , Anexina A1/farmacología , Antiinflamatorios/farmacología , Cilios/enzimología , Cilios/patología , Ciclooxigenasa 2/metabolismo , Dioxolanos/administración & dosificación , Dioxolanos/farmacología , Endotoxinas , Ojo/efectos de los fármacos , Ojo/patología , Mediadores de Inflamación/metabolismo , Masculino , Modelos Biológicos , Monocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Péptidos/administración & dosificación , Péptidos/farmacología , Ratas Wistar , Receptores de Lipoxina/metabolismo , Uveítis/sangre , Uveítis/patologíaRESUMEN
Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti-VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off-label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti-VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti-VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti-VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and nanoparticles developed as ocular anti-VEGF delivery system.
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Inhibidores de la Angiogénesis/administración & dosificación , Productos Biológicos/administración & dosificación , Sistema de Administración de Fármacos con Nanopartículas/química , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacocinética , Productos Biológicos/química , Productos Biológicos/farmacocinética , Retinopatía Diabética/tratamiento farmacológico , Composición de Medicamentos/métodos , Liberación de Fármacos , Estabilidad de Medicamentos , Ojo/irrigación sanguínea , Ojo/efectos de los fármacos , Ojo/patología , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Nanopartículas/química , Neovascularización Patológica/patología , Oclusión de la Vena Retiniana/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Vancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid (VCM-DMPEI nanoparticles/HA) were synthesized as an adjuvant for the treatment of bacterial endophthalmitis. The nanoparticles were formulated by experimental statistical design, thoroughly characterized, and evaluated in terms of bactericidal activity and both in vitro and in vivo ocular biocompatibility. The VCM-DMPEI nanoparticles/HA were 154 ± 3 nm in diameter with a 0.197 ± 0.020 polydispersity index; had a + 26.4 ± 3.3 mV zeta potential; exhibited a 93% VCM encapsulation efficiency; and released 58% of the encapsulated VCM over 96 h. VCM and DMPEI exhibited a synergistic bactericidal effect. The VCM-DMPEI nanoparticles/HA were neither toxic to ARPE-19 cells nor irritating to the chorioallantoic membrane. Moreover, the VCM-DMPEI nanoparticles/HA did not induce modifications in retinal functions, as determined by electroretinography, and in the morphology of the ocular tissues. In conclusion, the VCM-DMPEI nanoparticles/HA may be a useful therapeutic adjuvant to treat bacterial endophthalmitis.
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Endoftalmitis/tratamiento farmacológico , Polietileneimina/análogos & derivados , Vancomicina/farmacología , Antibacterianos/farmacología , Línea Celular , Portadores de Fármacos , Liberación de Fármacos , Ojo/efectos de los fármacos , Humanos , Ácido Hialurónico/metabolismo , Ácido Hialurónico/farmacología , Nanopartículas , Tamaño de la Partícula , Polietileneimina/química , Polietileneimina/farmacología , Vancomicina/químicaRESUMEN
BACKGROUND: Bilateral retinoblastoma (Rb) treatment remains a challenge for ophthalmologists and pediatric oncologists despite new therapeutic strategies for eye preservation. The purpose of this work is to evaluate treatment outcomes in patients who underwent eye salvage treatment at a single-center prior to the chemotherapy in situ era. PROCEDURE: We followed a cohort of 88 consecutive Rb patients diagnosed at Hospital Infantil de México between November 2000 and June 2014. Eye salvage treatment consisted of systemic chemotherapy plus focal therapy planned by a multidisciplinary team. Unresponsive tumors were treated with episcleral brachytherapy and external beam radiotherapy (EBRT). RESULTS: A total of 96 eyes underwent eye salvaging therapy. Seventy-eight eyes (81%) were salvaged. Seven patients (8%) required brachytherapy and 34 patients (39%) underwent EBRT. Thirty-three of 78 preserved eyes (42%) achieved normal visual acuity: 5/27 (20%) in radiated patients and 28/51 (61%) in nonradiated patients. Eight patients developed secondary primary malignancies; however, those treated with EBRT did not have a significantly increased risk when compared with nonirradiated patients (OR: 1.66; P = 0.492). The overall survival rate was 86% (95% CI, 76%-92%) after a mean follow-up of 10 years. CONCLUSIONS: Eye preservation, long-term tumor control, and functional visual acuity could be maintained in many child and adolescent Rb survivors. Our data suggest that ocular radiotherapy can be used as consolidation treatment when other recently developed therapies with potentially fewer side effects are not available. Multidisciplinary management of Rb is mandatory to obtain cancer control during eye salvage treatment.
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Ojo/efectos de los fármacos , Ojo/efectos de la radiación , Neoplasias Orbitales/terapia , Tratamientos Conservadores del Órgano/métodos , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Terapia Recuperativa , Quimioradioterapia/métodos , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , México , Neoplasias Orbitales/patología , Pronóstico , Neoplasias de la Retina/patología , Retinoblastoma/patología , Agudeza VisualRESUMEN
The tropical estuarine guppy Poecilia vivipara was used to address fish early life stage toxicity caused by the antifouling contaminant tributyltin. Six-day-old P. vivipara were exposed for 7 d to control water and waterborne tributyltin at 15.8, 83.8, 716, and 818 ng tin (Sn) L-1 . After exposure, swimming, feeding, growth, and eye histological endpoints were evaluated. Histopathological analysis of the retinal pigment epithelium (RPE) indicated alterations in pigment positioning at all tributyltin concentrations. A dose-dependent increase in photoreceptor layer disorganization and iris melanin hyperpigmentation was verified, and high frequencies of RPE invaginations and iris epithelial cell atrophy were observed even at the lowest exposure concentration of 15.8 ng Sn L-1 . At the highest exposure level (818 ng Sn L-1 ) fish also presented reductions in swimming speed, swimming resistance, daily capture of Artemia nauplii, and growth in weight of 85, 60, 33, and 56% relative to controls, respectively. This association between retinal histopathology and reduced swimming and foraging behavior can reduce recruitment to the adult population. Environ Toxicol Chem 2020;39:1953-1963. © 2020 SETAC.
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Conducta Animal/efectos de los fármacos , Desinfectantes/toxicidad , Ojo/efectos de los fármacos , Poecilia/crecimiento & desarrollo , Reproducción/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Ojo/patología , Retina/efectos de los fármacos , Retina/parasitología , NataciónRESUMEN
ABSTRACT Purpose: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea. Methods: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment. Results: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance. Conclusion: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.
RESUMO Objetivos: Comparar o impacto das alterações oculares entre o tratamento sistêmico de doxiciclina e isotretinoína em baixa dosagem em pacientes com rosácea papulopustulosa moderada a grave. Métodos: Os pacientes form randomizados para receber isotretinoína 0,3 a 0,4 mg/kg (grupo A) ou doxiciclina 100mg/dia (grupo B) por 16 semanas. Os sintomas oculares foram pesquisados e avaliados, incluindo melhor acuidade visual corrigida, teste de Schirmer, tempo de ruptura do filme lacrimal, coloração de rosa bengala e graduação da disfunção de glândula de Meibomius. Os pacientes foram novamente testados no final do tratamento. Resultados: O presente estudo incluiu 39 pacientes (30 mulheres e 9 homens). A melhor acuidade visual corrigida foi >20/30 em >90% dos pacientes em ambos os grupos e não se alterou após o tratamento. A melhora dos sintomas oculares e da disfunção de glândula de Meibomius foi mais pronunciada no grupo B (p<0,05) após o tratamento; as demais variáveis não atingiram significância estatística. Conclusão: A doxiciclina melhorou a disfunção de glândula de Meibomius, os sintomas oculares e a superfície ocular de pa cientes com rosácea. Mesmo que alguns pacientes tenham piorado a disfunção e os sintomas da glândula de Meibomius, nenhum indivíduo apresentou complicações graves após a admi nistração de baixas doses de isotretinoína.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Isotretinoína/administración & dosificación , Doxiciclina/administración & dosificación , Rosácea/tratamiento farmacológico , Fármacos Dermatológicos/administración & dosificación , Disfunción de la Glándula de Meibomio/tratamiento farmacológico , Antibacterianos/administración & dosificación , Índice de Severidad de la Enfermedad , Agudeza Visual , Administración Oral , Resultado del Tratamiento , Rosácea/fisiopatología , Ojo/efectos de los fármacos , Disfunción de la Glándula de Meibomio/fisiopatología , Glándulas Tarsales/efectos de los fármacosRESUMEN
PURPOSE: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea. METHODS: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment. RESULTS: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance. CONCLUSION: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.
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Antibacterianos/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Doxiciclina/administración & dosificación , Isotretinoína/administración & dosificación , Disfunción de la Glándula de Meibomio/tratamiento farmacológico , Rosácea/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Ojo/efectos de los fármacos , Femenino , Humanos , Masculino , Disfunción de la Glándula de Meibomio/fisiopatología , Glándulas Tarsales/efectos de los fármacos , Persona de Mediana Edad , Rosácea/fisiopatología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Agudeza Visual , Adulto JovenRESUMEN
Air pollution represents a major health problem in megacities, bringing about 8 million deaths every year. The aim of the study was to evaluate in vivo the ocular and respiratory mucosa biological response after chronic exposure to urban air particles from Buenos Aires (UAP-BA). BALB/c mice were exposed to UAP-BA or filtered air for 1, 6, 9, and 12 months. After exposure, histology, histomorphometry, and IL-6 proinflammatory cytokine level were evaluated in the respiratory and ocular mucosa. Total cell number and differential cell count were determined in the brochoalveolar lavage fluid. In the lung, chronic exposure to UAP-BA induced reduction of the alveolar space, polymorhonuclear cell recruitment, and goblet cell hyperplasia. In the ocular surface, UAP-BA induced an initial mucin positive cells rise followed by a decline through time, while IL-6 level increased at the latest point-time assayed. Our results showed that the respiratory and the ocular mucosas respond differently to UAP-BA. Being that lung and ocular mucosa diseases may be triggered and/or exacerbated by chronic exposure to urban air PM, the inhabitants of Buenos Aires whom are chronically exposed to environmental urban air pollution may be considered a subpopulation at risk. Based on our results, we propose the ocular mucosa as a reliable and more accessible surrogate for pulmonary mucosa environmental toxicity that might also serve as an earlier biomarker for air pollution adverse impact on health.
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Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Ojo/efectos de los fármacos , Pulmón/efectos de los fármacos , Membrana Mucosa/efectos de los fármacos , Contaminación del Aire/análisis , Animales , Argentina , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar/citología , Ojo/patología , Femenino , Interleucina-6/análisis , Interleucina-6/genética , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Material Particulado/efectos adversos , Material Particulado/análisis , Material Particulado/química , Pruebas de Toxicidad Crónica , UrbanizaciónRESUMEN
Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 × 105 cells (4 µL) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 µmol/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 µmol/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity.
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Antibacterianos/administración & dosificación , Péptidos Catiónicos Antimicrobianos/química , Proteínas de Artrópodos/administración & dosificación , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Queratitis/tratamiento farmacológico , Soluciones Oftálmicas/administración & dosificación , Venenos de Araña/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Administración Tópica , Animales , Antibacterianos/toxicidad , Proteínas de Artrópodos/toxicidad , Pollos , Membrana Corioalantoides/efectos de los fármacos , Ojo/efectos de los fármacos , Ojo/inmunología , Ojo/patología , Femenino , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Soluciones Oftálmicas/toxicidad , Conejos , Venenos de Araña/toxicidad , Staphylococcus aureusRESUMEN
Despite the wide range of diseases affecting the eye, ocular bioavailability remains a challenge in ophthalmic drug delivery. Nowadays an extensive variety of polymers are being explored to develop colloidal drug carriers which show better performance than the more popular drug solutions. For instance, regardless of the type of polymer used, these systems prolong the residence time of the drug in the absorption site with respect to conventional aqueous eye drops which are rapidly cleared from eye surface. Furthermore, colloidal drug carriers can be internalized by cells. In addition, positively charged particles penetrate the cornea more effectively than neutral or negatively charged ones. These phenomena lead to higher ocular bioavailability. This review overviews the different polymers available to produce drug-loaded gels, microparticles and nanoparticles, highlighting the advantageous features and biocompatibility of each polymer and the major achievements in the field of ocular delivery. In addition, the design of more complex delivery systems that combine several delivery platforms is presented. Finally, regulatory aspects relevant to the clinical translation of advanced ophthalmic drug delivery systems are also discussed. All together, this manuscript is aimed at guiding pharmaceutical research and development towards the rationale polymer selection to produce drug delivery systems that improve the performance of drugs for the therapy of ophthalmic diseases.
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Portadores de Fármacos/química , Oftalmopatías/tratamiento farmacológico , Preparaciones Farmacéuticas/administración & dosificación , Polímeros/química , Administración Oftálmica , Animales , Disponibilidad Biológica , Sistemas de Liberación de Medicamentos/métodos , Ojo/efectos de los fármacos , Ojo/metabolismo , Oftalmopatías/metabolismo , Humanos , FarmacocinéticaRESUMEN
Galectin-1 (Gal-1) is a ß-galactoside-binding protein with diverse biological activities in the pathogenesis of inflammation, however the mechanisms by which Gal-1 modulates cellular responses in allergic inflammatory processes have not been fully determined. In this study, we evaluated the therapeutic potential of Gal-1 eye drops in an experimental model of conjunctivitis. Wistar rats received a topical application of compound (C)48/80 (100â¯mg/ml) into right eyes and a drop of vehicle into the contralateral eye. Another group of rats received Gal-1 (0.3 or 3⯵g/eye) or sodium cromoglycate (SCG; 40â¯mg/ml) in both eyes and, after 15â¯min, right eye was challenged with C48/80. Conjunctivitis-induced by C48/80 was characterized by severe eyelid oedema and tearing, but clinical signs were ameliorated by eye drop doses of both Gal-1 (0.3/3⯵g) and SCG. As expected, an increased proportion of degranulated mast cells (62%, Pâ¯<â¯0.01) and lower histamine levels were observed after 6â¯h of C48/80 challenge, compared to control (32%). This effect was abrogated by Gal-1 and SCG, which reduced mast cell degranulation (31-36%), eosinophil migration and eosinophil peroxidase levels in the eyes. Gal-1 (3⯵g) and SCG treatments also decreased IL-4 levels, as well as activation of mitogen activated protein kinases compared to untreated C48/80 eyes. Our findings suggest that Gal-1 eye drops represent a new therapeutic strategy for ocular allergic inflammation.
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Antialérgicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Conjuntivitis Alérgica/tratamiento farmacológico , Galectina 1/uso terapéutico , Animales , Antialérgicos/administración & dosificación , Antiinflamatorios/administración & dosificación , Degranulación de la Célula/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Conjuntivitis Alérgica/inducido químicamente , Conjuntivitis Alérgica/inmunología , Conjuntivitis Alérgica/patología , Citocinas/inmunología , Eosinófilos/efectos de los fármacos , Eosinófilos/enzimología , Eosinófilos/fisiología , Ojo/efectos de los fármacos , Ojo/inmunología , Ojo/patología , Galectina 1/administración & dosificación , Histamina/inmunología , Mastocitos/efectos de los fármacos , Mastocitos/fisiología , Proteínas Quinasas Activadas por Mitógenos/inmunología , Soluciones Oftálmicas , Peroxidasas/metabolismo , Ratas Wistar , p-Metoxi-N-metilfenetilaminaRESUMEN
PURPOSE: To investigate the potential effects of chronic exposure to a nasal decongestant and its excipients on ocular tissues using an experimental rat model. METHODS: Sixty adult male Wistar rats were randomized into six groups. The first two groups were control (serum physiologic) and Otrivine® groups. The remaining four groups received the Otrivine excipients xylometazoline, benzalkonium chloride, sorbitol, and ethylene diamine tetra acetic acid. Medications were applied into both nostrils twice a day for 8 weeks. Before the rats were sacrificed, epithelial staining, the Schirmer test, and intraocular pressure measurements were performed under ketamine/xylasine anesthesia (50 and 5 mg/kg, respectively). RESULTS: Epithelial defects and dry eye were common findings in all study groups. Cataracts developed in two cases clinically. Histopathological evaluation revealed many different pathological alterations in all parts of the ocular tissues such as corneal edema, polypoid proliferation and hyalinization of the vessel wall, cystic formation of the lens, retinal nerve fiber layer degeneration, and corpora amylacea formation of the lacrimal gland. CONCLUSIONS: Prolonged usage of the nasal decongestant xylometazoline and its excipients may cause ophthalmic problems such as dry eyes, corneal edema, cataracts, retinal nerve fiber layer, and vascular damage in rats. Although these results were obtained from experimental animals, ophthalmologists should keep in mind the potential ophthalmic adverse effects of this medicine and/or its excipients and exercise caution with drugs containing xylometazoline, ethylene diamine tetra acetic acid, benzalkonium chloride and sorbitol for patients with underlying ocular problems.
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Oftalmopatías/inducido químicamente , Ojo/efectos de los fármacos , Imidazoles/efectos adversos , Descongestionantes Nasales/efectos adversos , Mucosa Nasal/efectos de los fármacos , Animales , Compuestos de Benzalconio/efectos adversos , Modelos Animales de Enfermedad , Ácido Edético/efectos adversos , Ojo/patología , Oftalmopatías/patología , Presión Intraocular , Masculino , Mucosa Nasal/patología , Distribución Aleatoria , Ratas Wistar , Índice de Severidad de la EnfermedadRESUMEN
ABSTRACT Purpose: To investigate the potential effects of chronic exposure to a nasal decongestant and its excipients on ocular tissues using an experimental rat model. Methods: Sixty adult male Wistar rats were randomized into six groups. The first two groups were control (serum physiologic) and Otrivine® groups. The remaining four groups received the Otrivine excipients xylometazoline, benzalkonium chloride, sorbitol, and ethylene diamine tetra acetic acid. Medications were applied into both nostrils twice a day for 8 weeks. Before the rats were sacrificed, epithelial staining, the Schirmer test, and intraocular pressure measurements were performed under ketamine/xylasine anesthesia (50 and 5 mg/kg, respectively). Results: Epithelial defects and dry eye were common findings in all study groups. Cataracts developed in two cases clinically. Histopathological evaluation revealed many different pathological alterations in all parts of the ocular tissues such as corneal edema, polypoid proliferation and hyalinization of the vessel wall, cystic formation of the lens, retinal nerve fiber layer degeneration, and corpora amylacea formation of the lacrimal gland. Conclusions: Prolonged usage of the nasal decongestant xylometazoline and its excipients may cause ophthalmic problems such as dry eyes, corneal edema, cataracts, retinal nerve fiber layer, and vascular damage in rats. Although these results were obtained from experimental animals, ophthalmologists should keep in mind the potential ophthalmic adverse effects of this medicine and/or its excipients and exercise caution with drugs containing xylometazoline, ethylene diamine tetra acetic acid, benzalkonium chloride and sorbitol for patients with underlying ocular problems.
RESUMO Objetivo: Investigar os possíveis efeitos da exposição crônica de descongestionante nasal e seus excipientes em tecidos oculares, utilizando um modelo experimental com ratos. Métodos: Sessenta ratos Wistar adultos machos foram divididos aleatoriamente em seis grupos. Os primeiros dois grupos foram controle (soro fisiológico) e Otrivina®. Os quatro grupos restantes receberam os excipientes de Otrivina, tais como Xilometazolina, Benzalcônio, Sorbitol e Ácido Etilenodiamino Tetracético (EDTA). Os medicamentos foram aplicados em ambas as narinas dos ratos, duas vezes ao dia, durante 8 semanas. Antes que os ratos fossem sacrificados, a coloração epitelial, o teste de Schirmer e a medida da pressão intraocular foram realizados sob anestesia com Ketamina/Xilasina (50 e 5 mg/kg, respectivamente). Resultados: Defeitos epiteliais e olho seco foram achados comuns nos grupos de estudo. A catarata desenvolveu-se clinicamente em dois casos. A avaliação histopatológica revelou a existência de alterações em todas as partes dos tecidos oculares, tais como edema de córnea, proliferação polipoide e hialinização da parede vascular, formação cística da lente, degeneração da camada de fibra nervosa da retina (RNFL) e formação de corpos amiláceos da glândula lacrimal. Conclusões: O uso prolongado do descongestionante nasal Xilometazolina e seus excipientes pode causar vários problemas oftalmológicos, como olho seco, edema de córnea, catarata, RNFL e dano vascular em ratos. Embora esses resultados tenham sido obtidos a partir de animais experimentais, os oftalmologistas devem ter em mente os potenciais efeitos oftalmológicos adversos desse medicamento e/ou de seus excipientes.
Asunto(s)
Animales , Masculino , Descongestionantes Nasales/efectos adversos , Ojo/efectos de los fármacos , Oftalmopatías/inducido químicamente , Imidazoles/efectos adversos , Mucosa Nasal/efectos de los fármacos , Compuestos de Benzalconio/efectos adversos , Índice de Severidad de la Enfermedad , Distribución Aleatoria , Ácido Edético/efectos adversos , Ratas Wistar , Modelos Animales de Enfermedad , Ojo/patología , Oftalmopatías/patología , Presión Intraocular , Mucosa Nasal/patologíaRESUMEN
RESUMO Objetivo: Comparar a eficácia fenilefrina a 10% aplicada pelo próprio paciente por vaporização em olho fechado em relação à instilação de gota em olho aberto em indivíduos que irão realizar exame de fundoscopia e avaliar o nível de dificuldade e a adequação técnica entre os métodos de administração. Métodos: Ensaio clínico controlado, randomizado e pareado realizado em 2014 envolvendo 100 olhos de 50 pacientes na Policlínica Ronaldo Gazolla - RJ, sem doenças oculares ou sistêmicas que comprometiam a dilatação pupilar. Os pacientes foram submetidos à instilação de 1 gota de fenilefrina a 10% e aplicação de vaporizador do mesmo midriático no olho contralateral. O olho em que se instilou o colírio permaneceu aberto, enquanto o olho vaporizado ficou fechado durante as aplicações da medicação. O diâmetro pupilar foi medido antes da aplicação, 10, 20 e 30 minutos após. O processo de instilação ou vaporização foi observado quanto a sua adequação técnica por um dos autores. Após o processo foi perguntado ao paciente questões pré-formuladas sobre a praticidade de ambos os métodos. Resultados: A diferença de midríase média entre os grupos de olhos avaliados em um determinado tempo foi no máximo 0,3 mm , o que não foi clinicamente ou estatisticamente significativo (ANOVA: F = 1,97 e p = 0,163609) . Porém, ao longo do tempo, a diferença entre o diâmetro da pupila no tempo inicial e no tempo de 30 minutos foi 1,15 mm para os olhos vaporizados e 1,58 mm para os olhos instilados com gotas (ANOVA: F = 129,22 e p ≤ 0,0001). Percentual de 60% dos pacientes tocaram a ponta do frasco de colírio nos olhos, enquanto que 12% tocaram o orifício na ponta do vaporizador com os dedos (p < 0,000001). Setenta de dois por cento (72%) consideraram a instilação de gotas fácil ou muito fácil enquanto 62% consideraram a vaporização em olho fechado fácil ou muito fácil (p = 0,238). Conclusão: A instilação de gotas em olhos abertos e a vaporização de olhos fechados da fenilefrina a 10% apresentou eficácia clínica semelhante. A vaporização foi mais segura e apresentou nível de dificuldade um pouco maior do que a instilação, apesar dos pacientes serem experientes para instilar gotas e inexperientes para vaporizar a medicação em olho fechado.
ABSTRACT Objective: To compare the effectiveness of phenylephrine 10% applied by a spray onto the eye closed over drop instillation onto an open eye on patients who will perform ophthalmoscopy and assess the level of difficulty and technical adequacy of the administration methods. Methods: The study was a clinical trial, controlled, randomized and paired, performed in 2014, involving 100 eyes of 50 patients in the Polyclinic Ronaldo Gazolla - RJ, with no ocular or systemic diseases that compromised the pupillary dilation. Patients underwent 10% phenylephrine eye drop instillation onto one open eye and spray application onto the other eye, which was closed. Pupillary diameter was measured before application and 10, 20, 30 minutes after. The process of instillation or vaporization was observed for its technical correctness by one of the authors. A questionnaire was asked to the patient about the difficulty of both methods after topical administration. Results: The average mydriasis difference between the eye groups assessed at a given time was at most 0.3 mm, which was not clinically or statistically significant (ANOVA: F = 1.97 and p = 0.163609). However, over time, the difference between the average pupil diameter before application and after 30 minutes was 1.15 mm to vaporized eyes and to 1.58 mm in eyes instilled with drops (ANOVA: F = 129, 22 and p ≤ 0.0001). Sixty per cent of patients touched the tip of the eye drop bottle onto the eye, while 12% touched the tip of the vaporizer with their fingers (p <0.000001). Seventy two percent (72%) considered the drops instillation easy or very easy, while 62% considered vaporization in a closed eye easy or very easy (p = 0.238). Conclusion: The instillation of drops phenylephrine 10% in open eyes and the vaporization onto closed eyes showed similar clinical efficacy. Vaporization was safer and a little more difficult than instillation, despite the patients being experienced for instilling drops and inexperienced to vaporize the medication in a closed eye.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Administración Tópica , Ojo/efectos de los fármacos , Midriáticos/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Fenilefrina , Instilación de Medicamentos , Ensayo Clínico Controlado Aleatorio , Encuestas y CuestionariosRESUMEN
Current treatments for Acanthamoeba keratitis are unspecific. Because of the presence of the resilient cyst form of the parasite, the infection is persistent. Silencing the key protein of cyst formation, glycogen phosphorylase, has shown potential for reducing encystment processes of the Acanthamoeba trophozoite. However, a suitable carrier to protect and deliver siRNA sequences is still needed. DOTAP: DOPE:DSPE-PEG liposomes were prepared by three different techniques and used to associate a therapeutic siRNA sequence. Liposomes prepared by film hydration followed by membrane extrusion were considered the most adequate ones with average size of 250 nm and zeta potential of +45 mV, being able to associate siRNA for at least 24 hr in culture medium. siRNA-liposomes could inhibit up to 66% of the encystment process. Cell viability studies demonstrated MTT reduction capacity higher than 80% after 3 hr incubation with this formulation. After 24 hr of incubation, LDH activity ranged for both the formulations from around 4% to 40%. In vivo tolerance studies in mice showed no macroscopic alteration in the eye structures up to 24 hr after eight administrations during 1 day. Histological studies showed regular tissue architecture without any morphological alteration. Overall, these results suggest that the formulations developed are a promising new strategy for the treatment of ocular keratitis caused by Acanthamoeba spp.
Asunto(s)
Acanthamoeba/efectos de los fármacos , Córnea/efectos de los fármacos , Liposomas/química , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/farmacología , Acanthamoeba/enzimología , Acanthamoeba/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Córnea/metabolismo , Córnea/parasitología , Córnea/patología , Ojo/efectos de los fármacos , Ojo/metabolismo , Ojo/parasitología , Ojo/patología , Glucógeno Fosforilasa/antagonistas & inhibidores , Glucógeno Fosforilasa/genética , Glucógeno Fosforilasa/metabolismo , Humanos , Liposomas/toxicidad , Masculino , Ratones , Tamaño de la Partícula , Proteínas Protozoarias/antagonistas & inhibidores , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/químicaRESUMEN
The aim of this study is to assess the change in intraocular pressure after a road trip, in eyes with different levels of filling with gas tamponade. Five rabbit eyes were subject to pars plana vitrectomy and gas tamponade (filling percentage: 25%, 50%, and 100% of nonexpansile SF6, 100% saline solution, and 100% room air). A sixth eye was injected with 0.35 cc of undiluted SF6 without vitrectomy. Guided by global positioning system, they were driven to the highest point of the highway connecting Mexico City with Puebla city and back, stopping every 300 m to assess intraocular pressure. The rabbit's scleral rigidity and estimation for human eyes were done by using the Friedenwald nomogram. Maximum altitude was 3209 m (Δ949 m). There were significant differences in intraocular pressure on the rabbit eyes filled with SF6 at 100%, 50%, 25%, and 100% room air. Per every 100 m of altitude rise, the intraocular pressure increased by 1.53, 1.0046, 0.971, and 0.97 mmHg, respectively. Using the human Friedenwald rigidity coefficient, the human eye estimate for intraocular pressure change was 2.1, 1.8, 1.4, and 1.1 mmHg per every 100 m of attitude rise. Altitude changes have a significant impact on intraocular pressure. The final effect depends on the percentage of vitreous cavity fill and scleral rigidity.
Asunto(s)
Ojo/efectos de los fármacos , Ojo/fisiopatología , Presión Intraocular/fisiología , Hexafluoruro de Azufre/administración & dosificación , Altitud , Animales , Sistemas de Información Geográfica , Humanos , Presión Intraocular/efectos de los fármacos , Estudios Longitudinales , Modelos Animales , Estudios Prospectivos , Conejos , Vitrectomía/métodosRESUMEN
RESUMO Objetivo: Determinar o grau de dificuldade para instilação tópica ocular em idosos, com ou sem o auxílio de dispositivo de apoio facial, por meio de questionário. Observar qual método foi tecnicamente melhor para aplicação tópica ocular de gotas. Métodos: O estudo foi um ensaio clínico, controlado, randomizado e pareado, realizado em 50 pacientes idosos de setembro de 2015 a junho de 2016 na Policlínica Ronaldo Gazolla, Lapa-Rio de Janeiro. Um frasco de colírio Optive® foi acoplado ao dispositivo de apoio facial denominado Eyedrop®. Cada participante instilou o colírio com ou sem o auxílio do dispositivo em cada um dos olhos, sendo que a seleção ocular foi feita aleatoriamente. Foi perguntado ao paciente questões pré-formuladas sobre a dificuldade de ambos os métodos e a técnica de administração tópica ocular foi avaliada. Resultados: A instilação de gotas foi considerada difícil ou muito difícil por 10% dos idosos com o auxílio do dispositivo e por 36% sem o auxílio (p = 0,0047). Houve toque da ponta do colírio com os tecidos oculares em 64% dos pacientes que não usaram o Eyedrop® e em 4% dos que o utilizaram (p=0,000001). A maior dificuldade descrita na instilação tradicional foi acertar o olho com a gota (32%) e com o dispositivo de apoio foi entender seu uso(4%). Conclusão: A maioria dos idosos instila colírios erroneamente, tocando a ponta do frasco em tecidos oculares, o que favorece sua contaminação. O dispositivo de apoio facial tornou mais segura e fácil a instilação.
ABSTRACT Objective: To determine the degree of difficulty for topical ocular instillation in the elderly, through a questionnaire, with or without the aid of facial support device. Observe which method was technically better to topical ocular application of drops. Methods: The study was a clinical trial, controlled, randomized and paired, which was conducted in 50 elderly patients from September 2015 to June 2016 at the Polyclinic Ronaldo Gazolla, Lapa, Rio de Janeiro. A Optive® eyedrop bottle was attached to a facial support device called Eyedrop®. Each participant instilled an eye drop with or without the device help in each of both eyes, wherein the eye selection was made randomly. He was asked to answer pre-formulated questions about the difficulty of both methods and the topical ocular administration technique was evaluated. Results: Eye drop instillation was difficult or very difficult for 10% of the elderly with the device aid and for 36% without it (p = 0.0047). There were bottle tip touch onto the ocular tissues in 64% of patients who did not use Eyedrop® and 4% who used it (p = 0.000001). The greatest difficulty described in traditional instillation was to head properly the eye drop (32%) and when the support device was used, it was to understand how to use it (4%). Conclusion: Most elderly instills eye drops mistakenly, touching the tip of the bottle onto ocular tissues, which favors contamination. The facial support device increased security and facility in instillation.