Influence of sex on chronic steroid-induced glaucoma: 24-Weeks follow-up study in rats.

The objective was to evaluate ocular changes based on sex in steroid-induced glaucoma models in rats comparing healthy controls, over 24 weeks follow-up. Eighty-nine Long-Evans rats (38 males and 51 females) with steroid-induced glaucoma were analysed. Two steroid-induced glaucoma models were generated by injecting poly-co-lactic-glycolic acid microspheres loaded with dexamethasone (MMDEX model) and dexamethasone-fibronectin (MMDEXAFIBRO model) into the ocular anterior chamber. Intraocular pressure was measured by rebound tonometer Tonolab®. Neuroretinal function was analysed using dark- and light-adapted electroretinography (Roland consult® RETIanimal ERG), and structure was analysed using optical coherence tomography (OCT Spectralis, Heidelberg® Engineering) using Retina Posterior Pole, Retinal Nerve Fibre Layer and Ganglion Cell Layer protocols over 24 weeks. Males showed statistically (p < 0.05) higher intraocular pressure measurements. In both sexes and models neuroretinal thickness tended to decrease over time. In the MMDEX model, males showed higher IOP values and greatest percentage thickness loss in the Ganglion Cell Layer (p = 0.015). Females receiving MMDEXAFIBRO experienced large fluctuations in thickness, a higher percentage loss (on average) in Retina Posterior Pole (p = 0.035), Retinal Nerve Fibre Layer and Ganglion Cell Layer than aged-matched males, and the highest thickness loss rate by mmHg. Although no difference was found by sex in dark- and light-adapted electroretinography, increased amplitude in photopic negative response was found in MMDEX males and MMDEXAFIBRO females at 12 weeks. Although both glaucoma models used dexamethasone, different intraocular pressure and neuroretinal changes were observed depending on sex and other influential cofactors (fibronectin). Both sex and the induced glaucoma model influenced neuroretinal degeneration.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops.

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.

New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost.

The chronic use of hypotensive agents eventually leads to ocular surface damage and poor patient compliance during glaucoma management. Thus, new sustained drug delivery systems are needed. This work aimed to develop osmoprotective latanoprost-loaded microemulsion formulations as new potential glaucoma treatments with ocular surface protective properties. The microemulsions were characterized and latanoprost encapsulation efficacy determined. In-vitro tolerance, osmoprotective efficacy, cell internalization as well as cell-microemulsion interactions and distribution were performed. In vivo hypotensive activity was conducted in rabbits to assess intraocular pressure reduction and relative ocular bioavailability. Physicochemical characterization showed nanodroplet sizes within 20-30 nm, being in vitro tolerance within 80 and 100% viability in corneal and conjunctival cells. Besides, microemulsions exhibited higher protection under hypertonic conditions than untreated cells. Cell fluorescence lasted for 11 days after short exposure to coumarin-loaded microemulsions (5 min) showing extensive internalization in different cell compartments by electronic microscopy. In vivo studies exhibited that a single instillation of latanoprost-loaded microemulsions reduced the intraocular pressure for several days (4-6 days without polymer and 9-13 days with polymers). Relative ocular bioavailability was 4.5 and 19 times higher than the marketed formulation. These findings suggest the use of these microemulsions as potential combined strategies for extended surface protection and glaucoma treatment.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non–IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations.To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. (AU)

El término alergia ocular engloba un conjunto de enfermedades inflamatorias de la superficie ocular de origen inmunoalérgico, con distintos niveles de afectación y gravedad. Están causadas por una variedad de mecanismos inmunes, mediados o no por IgE y pueden involucrar a todos los componentes de la superficie ocular, incluyendo conjuntiva, córnea, párpados, película lagrimal y flora comensal. De estos trastornos, el más común es la enfermedad alérgica conjuntival. En su clasificación se incluyen distintas formas clínicas según el nivel de afectación y la presencia o no de cambios proliferativos en la conjuntiva palpebral, asociación con dermatitis atópica, y estímulos mecánicos por cuerpo extraño, incluyendo lentes de contacto. Las guías terapéuticas para el tratamiento de la conjuntivitis alérgica proponen un tratamiento escalonado, tanto en administración oftálmica como oral, en función de la gravedad de los síntomas, las comorbilidades alérgicas del paciente y el logro de un control adecuado. En general, cuando los síntomas oculares predominan o se presentan de forma aislada, se prefieren las formulaciones oftálmicas de antihistamínicos de administración tópica y, dentro de estas, los colirios. Para mantener el equilibrio de la superficie ocular, las formulaciones tópicas oftálmicas deben mostrar una buena tolerancia. El objetivo principal de este artículo es revisar las características y otras propiedades de los excipientes (conservantes, tampones, agentes para ajustar el pH, viscosizantes, agentes humectantes o cosolventes, antioxidantes, isotonizantes y osmoprotectores) y sustancias activas (antihistamínicos oculares) que deben ser considerados cuando se formulan los preparados de administración tópica oftálmica de agentes antihistamínicos. (AU)

Development of an osmoprotective microemulsion as a therapeutic platform for ocular surface protection.

Self-emulsified osmoprotective ophthalmic microemulsions (O/A) were prepared by combining betaine/leucine, clusterin/oleanolic acid, and hyaluronic acid or Dextran. The microemulsions contained an internal oily phase (1.2%), an external aqueous phase (96.3%), cosolvents (1%), and surfactants (1.5%). Physicochemical characterization and in vivo and in vitro tolerance were analyzed. The formulations' osmoprotective in vitro activity was assayed in a hyperosmolar model in human corneal cells. Average internal phase sizes were 16-26 nm for the microemulsions including Dextran. Addition of hyaluronic acid increased the size range (25-39 nm). Addition of osmoprotectants did not change nanodroplet size. The formulations were isotonic (280-290 mOsm/L) with neutral pH (≈7) and zeta potential (-10 to 0 mV), low surface tension (≈35-40mN·m-1), and low viscosity (≈1 mPa·s), except for the microemulsions containing hyaluronic acid (≈4-5 mPa·s). SEM and cryo-TEM showed that all formulations exhibited sphere-shaped morphology with good cell tolerance (≈100%) and were stable at 8 °C for 9 months. Osmoprotective formulations were well tolerated in vitro and in vivo, protecting cells from hypertonic stress. We therefore developed stable microemulsions compatible with the ocular surface that could constitute a novel tool for treatment of ophthalmic diseases.

Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres.

PURPOSE: To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. METHODS: Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the right eye. Clinical signs and intraocular pressure (IOP) were weekly recorded. The structure of the retina and optic nerve was in vivo evaluated using optical coherence tomography (OCT) every two weeks and functionally using dark- and light-adapted electroretinography at 0-12-24 weeks. Histological studies were also performed. RESULTS: IOP progressively increased up to hypertension (23.22 ± 3.63 mmHg) in both eyes but did so later in left eyes. OCT quantified a decrease in full-thickness retina posterior pole (R), retinal-nerve-fiber layer (RNFL), and ganglion-cell layer (GCL) thickness up to 24 weeks. Right eyes showed higher neuroretinal thickness loss up to week 8. RNFL experienced the highest percentage thickness loss at the inferior-superior axis, while in GCL the inner sectors of the horizontal axis (Nasal-Temporal) suffered the greatest decrease in thickness. Retinal ganglion cell, photoreceptor, and intermediate cell functionality decreased over time. Increased deposition of collagen IV was also found in zonular fibers and the ciliary body. CONCLUSIONS: This work shows the usefulness of drug delivery systems, not to treat pathology but to induce it. Only two injections of Dex-PLGA-Ms in the anterior chamber of rat eyes were enough to progressively create ocular hypertension and subsequent functional and structural neuroretinal degeneration, at least over 6 months.

Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments.

PURPOSE: To develop an easy-to-perform combined model in human corneal epithelial cells (HCECs) and Balb/c mice macrophages J774.A1 (MP) for preliminary screening of potential ophthalmic therapeutic substances. METHODS: HCECs were exposed to different osmolarities (350-500 mOsm/L) and MTT assay was employed for cell survival and flow cytometry to assess apoptosis-necrosis and relative cell size (RCS) distribution. Effectiveness of Betaine, L-Carnitine, Taurine at different concentrations (ranging from 20 mM to 200 mM) was studied. Also, mucoadhesive polymers such as Hyaluronic acid (HA) and Hydroxypropylmethylcellulose (HPMC) (0.4 and 0.8%) were evaluated. Cells were pre-incubated with the compounds (8h) and then exposed to hyperosmotic stress (470 mOsm/L) for 16h. Moreover, anti-inflammatory activity was performed in LPS-stimulated MP. RESULTS: Exposure to hyperosmotic solutions between 450 and 500 mOsm/L promoted the highest cell death after 16h exposures (p < 0.0001) with a drop in viability to 34.96% ± 11.77 for 470 mOsm/L. Pre-incubation with Betaine at 150 mM and 200 mM provided the highest cell survival against hyperosmolarity (66.01% ± 3.65 and 65.90% ± 0.78 respectively) while HA 0.4% was the most effective polymer in preventing cell death (42.2% ± 3.60). Flow cytometry showed that Betaine and Taurine at concentrations between 150-200 mM and 20-80 mM respectively presented the highest anti-apoptotic activity. Also, HA and HPMC polymers reduced apoptotic-induced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. L-Carnitine 50 mM, Taurine 40 mM and HA 0.4% presented the highest TNF-α inhibition activity (60%) albeit all of them showed anti-inflammatory inhibition percentages higher than 20% CONCLUSIONS: HCECs hyperosmolar model combined with inflammatory conditions in macrophages allows the screening of osmoprotectants by simulating chronic hyperosmolarity (16h) and inflammation (24h).

Simultaneous co-delivery of neuroprotective drugs from multi-loaded PLGA microspheres for the treatment of glaucoma.

Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ±â€¯1.89 µm rendering them suitable for intravitreal injection using conventional 25G-32G needles. >62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC50 10.00 ±â€¯0.94 mM versus 6.89 ±â€¯0.82 mM in absence of DMQ-MSs) in R28 cell line. In vivo efficacy studies were performed using a well-established rodent model of chronic ocular hypertension (OHT), comparing single intravitreal injections of microspheres of DMQ-MSs to their equivalent individual single-drug loaded MSs mixture (MSsmix), empty MSs, no-treatment OHT only and naïve groups. Twenty one days after OHT induction, DMQ-MSs showed a significantly neuroprotective effect on RGCs compared to OHT only controls. No such protective effect was observed in empty MSs and single-drug MSs treated groups. This work suggests that multi-loaded PLGA MSs present a novel therapeutic approach in the management of retinal neurodegeneration conditions such as glaucoma.

Colirios hipotensores: la historia interminable. ¿Hay que considerar algo más que los principios activos? / Hypotensive eyedrops: The neverending story. Should we consider more than active principles?

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Pharmaceutical microscale and nanoscale approaches for efficient treatment of ocular diseases.

Efficient treatment of ocular diseases can be achieved thanks to the proper use of ophthalmic formulations based on emerging pharmaceutical approaches. Among them, microtechnology and nanotechnology strategies are of great interest in the development of novel drug delivery systems to be used for ocular therapy. The location of the target site in the eye as well as the ophthalmic disease will determine the route of administration (topical, intraocular, periocular, and suprachoroidal administration) and the most adequate device. In this review, we discuss the use of colloidal pharmaceutical systems (nanoparticles, liposomes, niosomes, dendrimers, and microemulsions), microparticles (microcapsules and microspheres), and hybrid systems (combination of different strategies) in the treatment of ophthalmic diseases. Emphasis has been placed in the therapeutic significance of each drug delivery system for clinical translation.

Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration.

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 µM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 µM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.

Preservation of biological activity of glial cell line-derived neurotrophic factor (GDNF) after microencapsulation and sterilization by gamma irradiation.

A main issue in controlled delivery of biotechnological products from injectable biodegradable microspheres is to preserve their integrity and functional activity after the microencapsulation process and final sterilization. The present experimental work tested different technological approaches to maintain the biological activity of an encapsulated biotechnological product within PLGA [poly (lactic-co-glycolic acid)] microspheres (MS) after their sterilization by gamma irradiation. GDNF (glial cell line-derived neurotrophic factor), useful in the treatment of several neurodegenerative diseases, was chosen as a labile model protein. In the particular case of optic nerve degeneration, GDNF has been demonstrated to improve the damaged retinal ganglion cells (RGC) survival. GDNF was encapsulated in its molecular state by the water-in-oil-in-water (W/O/W) technique or as solid according to the solid-in-oil-in-water (S/O/W) method. Based on the S/O/W technique, GDNF was included in the PLGA microspheres alone (S/O/W 1) or in combination with an antioxidant (vitamin E, Vit E) (S/O/W 2). Microspheres were sterilized by gamma-irradiation (dose of 25 kGy) at room and low (-78 °C) temperatures. Functional activity of GDNF released from the different microspheres was evaluated both before and after sterilization in their potential target cells (retinal cells). Although none of the systems proposed achieved with the goal of totally retain the structural stability of the GDNF-dimer, the protein released from the S/O/W 2 microspheres was clearly the most biologically active, showing significantly less retinal cell death than that released from either W/O/W or S/O/W 1 particles, even in low amounts of the neurotrophic factor. According to the results presented in this work, the biological activity of biotechnological products after microencapsulation and sterilization can be further preserved by the inclusion of the active molecule in its solid state in combination with antioxidants and using low temperature (-78 °C) during gamma irradiation exposure.

Interfacial interaction between transmembrane ocular mucins and adhesive polymers and dendrimers analyzed by surface plasmon resonance.

PURPOSE: Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. METHODS: The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). RESULTS: While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH(2)(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)>> CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). CONCLUSIONS: The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and dendrimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability.

Effects of corneal thickness on the intraocular penetration of travoprost 0.004%.

PURPOSE: To determine whether the intraocular penetration of travoprost 0.004% is affected by central corneal thickness. METHODS: Sixty-four patients who were scheduled for cataract surgery without any other ophthalmologic pathology of significance were enrolled in this study. At 120 min before surgery, one drop of travoprost 0.004% was instilled in the eye to be operated on. At the start of surgery, a sample of aqueous humour was extracted to subsequently determine its AL-5848 concentration. These concentrations were compared among three groups of patients established according to central corneal thickness measurements obtained by ultrasound pachymetry. RESULTS: Mean AL-5848 concentrations were 3.27±2.03 ng/ml in Group I (CCT<511 microns), 3.27±2.44 ng/ml in Group II (CCT≥511 and ≤574 microns), and 2.73±2.15 ng/ml in Group III (CCT>574 microns), indicating no significant differences among the groups. CONCLUSIONS: We were unable to demonstrate the greater or lesser penetration of travoprost depending on corneal thickness, which could explain differences in patient responses to this drug.

[Comparative study of the pressure lowering efficacy and variations in the ocular pulse amplitude between fixed combinations of dorzolamide/timolol and brinzolamide/timolol]. / Estudio comparativo de la eficacia hipotensora y de las variaciones en la amplitud de pulso ocular entre las combinaciones fijas dorzolamida/timolol y brinzolamida/timolol.

OBJECTIVE: To determine possible differences in the intraocular pressure (IOP) and ocular pulse amplitude (OPA) lowering capacity of the fixed drug combinations dorzolamide/timolol and brinzolamide/timolol. METHODS: In this cross-sectional study, one of the eyes of 25 healthy subjects was randomly assigned to treatment with dorzolamide/timolol and the other eye with brinzolamide/timolol. After instilling the drops, possible adverse effects (e.g., blurred vision, itching) were assessed in each eye. This assessment was repeated 30 minutes later. IOP and OPA were determined In each eye by dynamic contour tonometry at baseline and two hours following treatment. RESULTS: Both fixed drug combinations significantly reduced IOP and OPA with no differences detected between treatment groups. Among the adverse effects recorded, itching was significantly greater in the first assessment in the eyes treated with dorzolamide/timolol (P = .011). This difference was no longer apparent in the second assessment. CONCLUSIONS: Both fixed combinations were similarly effective in reducing intraocular pressure and ocular pulse amplitude. Adverse effects related to both treatments were mild and well-tolerated, though itching occurred most frequently in the eyes treated with dorzolamide/timolol.

Estudio comparativo de la eficacia hipotensora y de las variaciones en la amplitud de pulso ocular entre las combinaciones fijas dorzolamida/timolol y brinzolamida/timolol / Comparative study of the pressure lowering efficacy and variations in the ocular pulse amplitude between fixed combinations of dorzolamide/ timolol and brinzolamide/timolol

Objetivo: Evaluar las diferencias en cuanto a eficacia hipotensora y amplitud de pulso ocularentre las combinaciones fijas de dorzolamida/timolol y brinzolamida/timolol.Métodos: Estudio transversal en 25 sujetos sanos. En cada paciente uno de los ojos fue tratadocon la combinación fija dorzolamida/timolol y el otro con brinzolamida/timolol. La asignaciónfue realizada al azar en cada paciente. Tras la instilación, mediante una escala visualanalógica se evaluaron los posibles efectos adversos (visión borrosa, picor. . .) en cada uno delos ojos. Esta evaluación se repitió a los 30 minutos de la instilación. Mediante un tonómetrode contorno dinámico se registró la presión intraocular y la amplitud de pulso ocular a nivelbasal y a las dos horas de la instilación.Resultados: Ambas combinaciones fijas disminuyeron de forma significativa la presión intraoculary la amplitud de pulso ocular sin diferencias significativas entre los dos grupos detratamiento. De los acontecimientos adversos evaluados, el picor fue significativamentemayor en los ojos tratados con dorzolamida/timolol en la primera medida (p = 0,011). Estadiferencia desapareció en la segunda evaluación.Conclusiones: Ambas combinaciones fijas demostraron ser igualmente eficaces, produciendovariaciones similares y significativas en la amplitud de pulso ocular. Los efectos adversosfueron en ambos casos leves y bien tolerados presentándose únicamente el picor como másfrecuente en los ojos tratados con dorzolamida/timolol(AU)

Objective: To determine possible differences in the intraocular pressure (IOP) and ocular pulseamplitude (OPA) lowering capacity of the fixed drug combinations dorzolamide/timolol andbrinzolamide/timolol.Methods: In this cross-sectional study, one of the eyes of 25 healthy subjects wasrandomly assigned to treatment with dorzolamide/timolol and the other eye with brinzolamide/timolol. After instilling the drops, possible adverse effects (e.g., blurred vision,itching) were assessed in each eye. This assessment was repeated 30 minutes later. IOP andOPA were determined In each eye by dynamic contour tonometry at baseline and two hoursfollowing treatment.Results: Both fixed drug combinations significantly reduced IOP and OPA with no differencesdetected between treatment groups. Among the adverse effects recorded, itching wassignificantly greater in the first assessment in the eyes treated with dorzolamide/timolol(P = .011). This difference was no longer apparent in the second assessment.Conclusions: Both fixed combinations were similarly effective in reducing intraocular pressureand ocular pulse amplitude. Adverse effects related to both treatments were mild andwell-tolerated, though itching occurred most frequently in the eyes treated with dorzolamide/timolol(AU)

Random co-polymers based on the poloxamer Bayfit® 10WF15 for biomedical applications.

Random co-polymers were prepared from the poloxamer Bayfit(®) 10WF15 and their thermal and biological properties analyzed. The poloxamer was characterized, functionalized with methacrylate groups (Bayfit-MA) and further co-polymerized with 2-hydroxyethyl methacrylate (HEMA) with Bayfit-MA feed contents of 1, 5 and 10 wt%. Co-polymers were partially soluble in organic solvents and exhibited a single glass transition temperature indicative of a random monomer distribution in the macromolecular chains. In thermogravimetric studies the co-polymers showed two degradation stages, around 210 and 350 °C, respectively. The thermosensitive behaviour of the poloxamer was studied by turbidimetry. Cloud point temperatures of aqueous solutions of Bayfit(®) 10WF15 (0.5-5 wt%) ranged from 15 to 18 °C and for Bayfit(®) 10WF15 methacrylate (0.5-1 wt%) from 6 to 7 °C. DSC thermograms of hydrated co-polymers showed the typical endothermic peaks with phase transition temperatures close to that of physiological medium. The biocompatibility of initial poloxamer and derivatives was analyzed with human fibroblasts cultures. The IC(50) value of Bayfit(®) 10WF15 was 1.4 mg/ml. Cellular extracts of the co-polymers were not cytotoxic and cellular proliferation and DNA content depended on co-polymer composition.

Aplicación de la metodología de aprendizaje cooperativo a la materia de Biofarmacia y Farmacocinética / Implementation of the cooperative learning methodology to the Biopharmaceutics and Pharmacokinetics subject

La convergencia dentro del marco Europeo de Educación Superior plantea la necesidad de introducir cambios en el sistema educativo universitario. En este sentido, la formación en la universidad debe asegurar el desarrollo integral y continuo de los nuevos profesionales. El modelo tradicional de enseñanza ligado a conocimientos disciplinares ha de sustituirse por una formación en competencias ligadas al desempeño profesional y a un saber hacer cualificado para cada situación concreta. Metodologías activas como el aprendizaje cooperativo (AC) son reconocidas como estrategias idóneas para alcanzar estas competencias.En este entorno se plantea el objetivo de este trabajo como una experiencia de aprendizaje cooperativo que se está llevando a cabo con un grupo de alumnos de la asignatura de Biofarmacia y Farmacocinética en la Licenciatura de Farmacia. Este estudio forma parte del desarrollo de un proyecto de Innovación y Mejora de la Calidad Docente de la Universidad Complutense de Madrid (UCM 2009-276). Dentro del programa de la asignatura se han elegido aquellos temas que resultan más adecuados para los objetivos de esta modalidad de aprendizaje. El grupo en el que se ha llevado a cabo esta experiencia, es un grupo piloto (adscripción voluntaria para los alumnos) que cuenta con 63 alumnos. Se han formado 9 grupos de trabajo con la participación de 7 especialistas por grupo. Para la comunicación con los alumnos y la entrega de documentación de trabajo se ha utilizado el Campus Virtual de la UCM que utiliza la plataforma WebCT(AU)

The convergence in the European Higher Education Framework presents the need to make changes in the University Educational System. In this sense, the education in the University must ensure the all-round and continuous development of new professionals. The traditional model of education related to the knowledge of subjects must be substituted by the education in competences related to professional performance and qualification know-how for each particular situation. Active methodologies such as cooperative learning are recognized as suitable strategies to get those competences. In this environment, the objective of this work is presented as a cooperative learning experience that is carrying out with a group of students of Biopharmacy and Pharmacokinetic subject of the Pharmacy Grade. This study is part of the development of a Project of Innovation and Improvement of the Educational Quality in the Complutense University of Madrid. The topics that have been chosen from the whole program of the subject are the most suitable to reach the objectives of this learning method. This experience has been tested in a pilot group integrated by 63 voluntary students. Nine work groups have been formed with the participation of seven specialists in each group. The UCM Virtual Campus website (based on WebCT platform) has been used for communication with the students and documentation purposes(AU)

The effect of preservative-free HP-Guar on dry eye after phacoemulsification: a flow cytometric study.

PURPOSE: To assess the effect of hydroxypropyl (HP)-Guar added to regular post-phacoemulsification treatment in dry eye signs and symptoms, and its influence on the expression of various inflammatory markers by flow cytometry (FCM) in impression cytology specimens. METHODS: This prospective, interventional, single-centre study included 48 eyes of 48 patients with age-related cataract. After phacoemulsification, patients were randomised to the usual treatment group (UT), with 21 patients who received tobramycin and dexamethasone eye drops (Tobradex, Alcon Cusí, Spain), and the HP-Guar group, with 27 patients who received the UT plus preservative-free artificial tears (Systane UD, Alcon Cusí, Spain). Corneal and conjunctival staining with fluorescein and lissamine green, tear film break-up time (TBUT), Schirmer's I test with anaesthesia (Jones test), tear clearance, and ocular surface disease index (OSDI) were assessed preoperatively and 1 month after surgery. Besides, conjunctival impression cytology was performed in order to investigate inflammatory markers (CD3, CD11b, and HLA-DR) using FCM. RESULTS: HP-Guar group shows statistical better results compared with the UT group in TBUT (6.4+/-0.7 vs 9+/-2.5, P=0.0004), OSDI (11.5+/-8.2 vs 3.3+/-2.5, P=0.0002), ocular symptoms subscale (7.3+/-6.1 vs 1.7+/-1.8, P=0.0004), vision-related function subscale (2.2+/-1.8 vs 0.4+/-0.6, P=0.0002), CD3 (2.5+/-1.4 vs 1.1+/-1.1, P=0.011), and HLA-DR (6.8+/-4.5 vs 1.8+/-1.7, P=0.0002). CONCLUSION: The addition of HP-Guar to regular treatment after cataract surgery reduces ocular surface inflammation and dry eye signs and symptoms.