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1.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361825

RESUMO

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3',6'-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9'-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases.


Assuntos
Córnea/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanopartículas/administração & dosagem , Segmento Posterior do Olho/metabolismo , Compostos de Espiro/administração & dosagem , Animais , Córnea/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Segmento Posterior do Olho/efeitos dos fármacos , Coelhos , Compostos de Espiro/química
2.
Invest Ophthalmol Vis Sci ; 62(9): 9, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232257

RESUMO

Purpose: Glaucoma is a multifactorial disease, causing retinal ganglion cells (RGCs) and optic nerve degeneration. The role of diabetes as a risk factor for glaucoma has been postulated but still not unequivocally demonstrated. The purpose of this study is to clarify the effect of diabetes in the early progression of glaucomatous RGC dysfunction preceding intraocular pressure (IOP) elevation, using the DBA/2J mouse (D2) model of glaucoma. Methods: D2 mice were injected with streptozotocin (STZ) obtaining a combined model of diabetes and glaucoma (D2 + STZ). D2 and D2 + STZ mice were monitored for weight, glycemia, and IOP from 3.5 to 6 months of age. In addition, the activity of RGC and outer retina were assessed using pattern electroretinogram (PERG) and flash electroretinogram (FERG), respectively. At the end point, RGC density and astrogliosis were evaluated in flat mounted retinas. In addition, Müller cell reactivity was evaluated in retinal cross-sections. Finally, the expression of inflammation and oxidative stress markers were analyzed. Results: IOP was not influenced by time or diabetes. In contrast, RGC activity resulted progressively decreased in the D2 group independently from IOP elevation and outer retinal dysfunction. Diabetes exacerbated RGC dysfunction, which resulted independent from variation in IOP and outer retinal activity. Diabetic retinas displayed decreased RGC density and increased glial reactivity given by an increment in oxidative stress and inflammation. Conclusions: Diabetes can act as an IOP-independent risk factor for the early progression of glaucoma promoting oxidative stress and inflammation-mediated RGC dysfunction, glial reactivity, and cellular death.


Assuntos
Diabetes Mellitus Experimental/complicações , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Retina/fisiopatologia , Células Ganglionares da Retina/patologia , Animais , Axônios/patologia , Diabetes Mellitus Experimental/fisiopatologia , Eletrorretinografia , Glaucoma/diagnóstico , Glaucoma/etiologia , Camundongos , Camundongos Endogâmicos DBA , Retina/diagnóstico por imagem
3.
Int J Mol Sci ; 22(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919241

RESUMO

Glaucoma is a heterogeneous group of chronic neurodegenerative disorders characterized by a relatively selective, progressive damage to the retinal ganglion cells (RGCs) and their axons, which leads to axon loss and visual field alterations. To date, many studies have shown the role of various elements, mainly metals, in maintaining the balance of prooxidative and antioxidative processes, regulation of fluid and ion flow through cell membranes of the ocular tissues. Based on the earlier and current research results, their relationship with the development and progression of glaucoma seems obvious and is increasingly appreciated. In this review, we aimed to summarize the current evidence on the role of trace elements in the pathogenesis and prevention of glaucomatous diseases. Special attention is also paid to the genetic background associated with glaucoma-related abnormalities of physiological processes that regulate or involve the ions of elements considered as trace elements necessary for the functioning of the cells.


Assuntos
Glaucoma/metabolismo , Oligoelementos/metabolismo , Animais , Glaucoma/induzido quimicamente , Glaucoma/prevenção & controle , Humanos , Doenças Neurodegenerativas , Oligoelementos/farmacologia
4.
Gels ; 6(4)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33287457

RESUMO

Gel is a two-phase elastic colloidal material, consisting of a dispersed liquid incorporated in the solid phase [...].

5.
Biochem Pharmacol ; 180: 114199, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32798466

RESUMO

To investigate the role of P2X7 receptor to preserve retinal ganglion cells (RGCs) structure and function in a genetic mouse model (DBA/2J mouse) of age-related glaucomatous neurodegeneration. Chronic treatment with P2X7 receptor antagonist eye drops was carried out in order to assess RGCs function and density by pattern electroretinogram (PERG) and RBPMS immunostaining, respectively. Further, microglia activation was assessed in flat-mounted retina by using Iba-1 immunostaining. Untreated glaucomatous eyes displayed significant microglia activation, alteration of PERG signal, and RGCs loss. In the P2X7 receptor antagonist-treated eyes, the PERG signal was significantly (p < 0.05) improved compared to controls, along with a significant (p < 0.05) reduction in terms of retinal microglial activation, and remarkable preservation of RGCs density. Altogether, these findings demonstrated that topical treatment with a P2X7 receptor antagonist has a neuroprotective effect on RGCs in glaucomatous mice, suggesting an appealing pharmacological approach to prevent retinal degenerative damage in optic neuropathy.


Assuntos
Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Antagonistas do Receptor Purinérgico P2X/metabolismo , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Receptores Purinérgicos P2X7/metabolismo , Células Ganglionares da Retina/metabolismo , Animais , Eletrorretinografia/métodos , Glaucoma/patologia , Camundongos , Camundongos Endogâmicos DBA , Niacinamida/análogos & derivados , Niacinamida/metabolismo , Niacinamida/uso terapêutico , Piperazinas/metabolismo , Piperazinas/uso terapêutico , Células Ganglionares da Retina/patologia
6.
Nutrients ; 12(7)2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32605122

RESUMO

Flickering light increases metabolic demand in the inner retina. Flicker may exacerbate defective mitochondrial function in glaucoma, which will be reflected in the pattern electroretinogram (PERG), a sensitive test of retinal ganglion cell (RGC) function. We tested whether flicker altered the PERG of DBA/2J (D2) glaucomatous mice and whether vitamin B3-rich diet contributed to the flicker effect. D2 mice fed with either standard chow (control, n = 10) or chow/water enriched with nicotinamide (NAM, 2000 mg/kg per day) (treated, n = 10) were monitored from 3 to 12 months. The PERG was recorded with superimposed flicker (F-PERG) at either 101 Hz (baseline) or 11 Hz (test), and baseline-test amplitude difference (adaptation) evaluated. At endpoint, flat-mounted retinas were immunostained (RBPMS and mito-tracker). F-PERG adaptation was 41% in 3-month-old D2 and decreased with age more in control D2 than in NAM-fed D2 (GEE, p < 0.01). At the endpoint, F-PERG adaptation was 0% in control D2 and 17.5% in NAM-fed D2, together with higher RGC density (2.4×), larger RGC soma size (2×), and greater intensity of mitochondrial staining (3.75×). F-PERG adaptation may provide a non-invasive tool to assess RGC autoregulation in response to increased metabolic demand and test the effect of dietary/pharmacological treatments on optic nerve disorders.


Assuntos
Glaucoma/fisiopatologia , Niacinamida , Células Ganglionares da Retina , Adaptação Fisiológica/efeitos dos fármacos , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Eletrorretinografia , Camundongos , Camundongos Endogâmicos DBA , Niacinamida/administração & dosagem , Niacinamida/farmacologia , Estimulação Luminosa , Retina/efeitos dos fármacos , Retina/fisiologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/fisiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-32365891

RESUMO

Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Microbiologia Ambiental , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , COVID-19 , Infecções por Coronavirus/transmissão , Consultórios Odontológicos , Humanos , Edifícios de Consultórios Médicos , Pneumonia Viral/transmissão , Risco , SARS-CoV-2
8.
Sci Rep ; 10(1): 3972, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132582

RESUMO

Deletion of dystrobrevin binding protein 1 has been linked to Hermansky-Pudlak syndrome type 7 (HPS-7), a rare disease characterized by oculocutaneous albinism and retinal dysfunction. We studied dysbindin-1 null mutant mice (Dys-/-) to shed light on retinal neurodevelopment defects in HPS-7. We analyzed the expression of a focused set of miRNAs in retina of wild type (WT), Dys+/- and Dys-/- mice. We also investigated the retinal function of these mice through electroretinography (ERG). We found that miR-101-3p, miR-137, miR-186-5p, miR-326, miR-382-5p and miR-876-5p were up-regulated in Dys-/-mice retina. Dys-/- mice showed significant increased b-wave in ERG, compared to WT mice. Bioinformatic analysis highlighted that dysregulated miRNAs target synaptic plasticity and dopaminergic signaling pathways, affecting retinal functions of Dys-/- mice. Overall, the data indicate potential mechanisms in retinal neurodevelopment of Dys-/- mice, which may have translational significance in HSP-7 patients, both in terms of diagnostic/prognostic biomarkers and novel pharmacological targets.


Assuntos
Síndrome de Hermanski-Pudlak/tratamento farmacológico , Síndrome de Hermanski-Pudlak/metabolismo , MicroRNAs/metabolismo , Terapia de Alvo Molecular , Retina/efeitos dos fármacos , Retina/metabolismo , Animais , Biologia Computacional , Regulação da Expressão Gênica/efeitos dos fármacos , Síndrome de Hermanski-Pudlak/diagnóstico , Síndrome de Hermanski-Pudlak/genética , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico
9.
J Cell Physiol ; 234(10): 17295-17304, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30770549

RESUMO

To study the effects of curcumin on human retinal pigment epithelial (RPE) cells exposed to high glucose (HG) insult, we performed in vitro studies on RPE cells cultured both in normal and HG conditions to assess the effects of curcumin on the cell viability, nuclear factor erythroid 2-related factor 2 (Nrf2) expression, HO-1 activity, and ERK1/2 expression. RPE cells exposed to HG insult were treated with curcumin. The cell viability, apoptosis, HO-1 activity, ERK, and Nrf2 expression were evaluated. The data indicated that treatment with curcumin caused a significant decrease in terms of apoptosis. Further, curcumin was able to induce HO-1 expression via Nrf2 activation and counteracts the damage elicited by HG. The present study demonstrated that curcumin provides protection against HG-induced damage in RPE cells through the activation of Nrf2/HO-1 signaling that involves the ERK pathway, suggesting that curcumin may have therapeutic value in the treatment of diabetic retinopathy.


Assuntos
Curcumina/farmacologia , Células Epiteliais/efeitos dos fármacos , Glucose/farmacologia , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo
10.
Int J Mol Sci ; 19(1)2018 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-29342845

RESUMO

Blindness in glaucoma is the result of death of Retinal Ganglion Cells (RGCs) and their axons. RGC death is generally preceded by a stage of reversible dysfunction and structural remodeling. Current treatments aimed at reducing intraocular pressure (IOP) are ineffective or incompletely effective in management of the disease. IOP-independent neuroprotection or neuroprotection as adjuvant to IOP lowering in glaucoma remains a challenge as effective agents without side effects have not been identified yet. We show in DBA/2J mice with spontaneous IOP elevation and glaucoma that the lifespan of functional RGCs can be extended by preconditioning RGCs with retrobulbar lidocaine in one eye at four months of age that temporary blocks RGC axonal transport. The contralateral, PBS-injected eye served as control. Lidocaine-induced impairment of axonal transport to superior colliculi was assessed by intravitreal injection of cholera toxin B. Long-term (nine months) effect of lidocaine were assessed on RGC electrical responsiveness (PERG), IOP, expression of relevant protein (BDNF, TrkB, PSD95, GFAP, Synaptophysin, and GAPDH) and RGC density. While lidocaine treatment did not alter the age-related increase of IOP, TrkB expression was elevated, GFAP expression was decreased, RGC survival was improved by 35%, and PERG function was preserved. Results suggest that the lifespan of functional RGCs in mouse glaucoma can be extended by preconditioning RGCs in early stages of the disease using a minimally invasive treatment with retrobulbar lidocaine, a common ophthalmologic procedure. Lidocaine is inexpensive, safe and is approved by Food and Drug Administration (FDA) to be administered intravenously.


Assuntos
Anestésicos/farmacologia , Glaucoma/prevenção & controle , Neuroproteção/efeitos dos fármacos , Animais , Transporte Axonal/efeitos dos fármacos , Eletrorretinografia , Glaucoma/patologia , Glaucoma/fisiopatologia , Pressão Intraocular , Lidocaína/farmacologia , Camundongos Endogâmicos DBA , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Fatores de Tempo
11.
Eur J Pharmacol ; 787: 72-7, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26845696

RESUMO

To set up a retinal degenerative model in rat that mimics pathologic conditions such as age-related macular degeneration (AMD) using amyloid-ß (Aß) oligomers, and assess the effect of TGF-ß1. Sprague-Dawley male rats were used. Human Aß1-42 oligomers were intravitreally (ITV) injected (10µM) in the presence or in the absence of recombinant human TGF-ß1 (1ng/µl ITV injected). After 48h, the animals were sacrificed and the eyes removed and dissected. The apoptotic markers Bax and Bcl-2 were assessed by western blot analysis in retina lysates. Gene-pathway network analysis was carried out in order to identify pathways involved in AMD. Treatment with Aß oligomers induced a strong increase in Bax protein level (about 4-fold; p<0.01) and a significant reduction in Bcl-2 protein level (about 2-fold; p<0.05). Co-injection of TGF-ß1 triggered a significant reduction of Bax protein induced by Aß oligomers. Bioinformatic analysis revealed that Bcl-2 and PI3K-Akt are the most connected nodes, for genes and pathways respectively, in the enriched gene-pathway network common to AMD and Alzheimer disease (AD). Overall, these data indicate that ITV injection of Aß1-42 oligomers in rat induces molecular changes associated with apoptosis in rat retina, highlighting a potential pathogenetic role of Aß oligomers in AMD. Bioinformatics analysis confirms that apoptosis pathways can take part in AMD. Furthermore, these findings suggest that human recombinant TGF-ß1 can prevent retinal damage elicited by Aß oligomers.


Assuntos
Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/toxicidade , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidade , Multimerização Proteica , Retina/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Animais , Citoproteção/efeitos dos fármacos , Humanos , Masculino , Estrutura Secundária de Proteína , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Retina/citologia , Proteína X Associada a bcl-2/metabolismo
12.
Front Pharmacol ; 6: 280, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26635610

RESUMO

PURPOSE: Colostrum has been proposed to treat severe dryness and problematic eye lesions showing a beneficial effect. The aim of the study was to investigate the effect of 2-fucosyl-lactose, a natural sugar present in the human colostrum, in an experimental dry eye. METHODS: Dry eye was induced in adult male New Zealand albino rabbits by topical administration of 1% atropine. Tear volume (Schirmer's test), tear film breakup time (TBUT), corneal staining and tear osmolarity were assessed. Fucosyl-lactose eye drops was instilled at different concentrations (0.01, 0.1, and, 1%). RESULTS: After 24 h from first atropine administration, tear volume and TBUT values were significantly improved in groups treated with 2-fucosyl-lactose in a dose-dependent manner. Tear volume increased from 5.25 to 10.75 mm and TBUT values from 8.75 to 34.5 s with 0.01% or 1% 2-fucosyl-lactose treatment, respectively. No changes were observed in terms of corneal staining among the all groups treated with 2-fucosyl-lactose. Atropine instillation caused an increase of tear osmolarity (428 mOsm/L), which was reversed by topical treatment with 2-fucosyl-lactose at all doses. CONCLUSION: The present study demonstrated that 2-fucosyl-lactose, a human milk oligosaccharide, has protective effect on tear film stability.

13.
Prog Brain Res ; 220: 217-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26497793

RESUMO

Glaucoma is a progressive optic neuropathy and is one of the leading causes of blindness in the industrialized countries. The aim of this study is to investigate microRNA (miRNA) regulation in glaucoma and other neurodegenerative diseases, that share similar pathways, by means of in silico approaches such as bibliographic search and access to bioinformatic resources. First of all, data mining was carried out on Human miRNA Disease Database (HMDD) and miR2Disease databases. Then, predictions of deregulated miRNAs were carried out accessing to microrna.org database. Finally, the potential combinatorial effect of miRNAs, on regulation of biochemical pathways, was studied by an enrichment analysis performed by DIANA-miRPath v.2.0. We found, from literature search, 8 deregulated miRNAs in glaucoma and 9 and 23 in age-related macular degeneration (AMD) and Alzheimer's disease (AD), respectively. One miRNA is commonly deregulated in glaucoma and AMD (miR-23a). Two miRNAs (miR-29a, miR-29b) are common to glaucoma and AD, and four miRNAs were identified to be commonly deregulated in AMD and AD (miR-9, miR-21, miR-34a, miR-146a). The match of the miRNA common to glaucoma and the other two neurodegenerative diseases (AMD and AD) did not generate any output. Enrichment of information has been reached through miRNAs prediction: 88 predicted miRNAs are common to glaucoma and AMD, 19 are common to glaucoma and AD, and 9 are common to AMD and AD. Indeed, predicted miRNAs common to the three neurodegenerative diseases are nine (miR-107, miR-137, miR-146a, miR-181c, miR-197, miR-21, miR-22, miR-590, miR-9). DIANA-miRPath predicted that those nine miRNAs might regulate pathways involved in inflammation. The findings hereby obtained provide a valuable hint to assess deregulation of specific miRNA, as potential biomarkers and therapeutic targets, in glaucoma and other neurodegenerative diseases by means of preclinical and clinical studies.


Assuntos
Glaucoma , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Glaucoma/diagnóstico , Glaucoma/genética , Glaucoma/metabolismo , Humanos , Doenças Neurodegenerativas/etiologia , Doenças Retinianas/genética , Doenças Retinianas/patologia
14.
Eur J Pharmacol ; 752: 78-83, 2015 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-25704612

RESUMO

In this study, we report the design and synthesis of novel hybrids of caffeic acid phenetyl ester (CAPE) and non-steroidal anti-inflammatory drugs (NSAIDs). We assessed their effects on an experimental ocular inflammation in New Zealand rabbits. The formulations of CAPE-aspirin and CAPE-indomethacin hybrids were topical instilled in the rabbit׳s eye. Afterwards, the anti-inflammatory activity was evaluated by grading the clinical signs and by assessing the inflammatory cell count, protein, PGE2 and TNFα levels in the aqueous humor. Furthermore, ocular tolerability of hybrids formulations was evaluated in a separate set of animals by using a modified Draize test. The ocular inflammation in the control group was significantly higher than in both the hybrid-treated groups, as indicated by clinical grading and biomarkers assessment. However, only the CAPE-aspirin hybrid reduced, in a significant dose-dependent manner, the ocular inflammation elicited by paracentesis. CAPE-indomethacin hybrid was able to significantly attenuate the clinical grading and the PGE2 aqueous levels only at the highest dose (0.1%). CAPE-aspirin significantly reduced PGE2 and TNFα levels in the aqueous humor as well as proteins and PMNs. Finally, all formulations showed no ocular irritation compared with vehicle-treated group. In conclusion, CAPE-aspirin shows full anti-inflammatory efficacy in experimental model of ocular inflammation demonstrating an optimal pharmacological and safety profile. Taken together these data indicate that CAPE-aspirin hybrid represents a valid and safe new chemical entity potentially useful for the treatment of ocular inflammation.


Assuntos
Anti-Inflamatórios não Esteroides/química , Aspirina/química , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Oftalmopatias/tratamento farmacológico , Oftalmopatias/patologia , Indometacina/química , Álcool Feniletílico/análogos & derivados , Animais , Ácidos Cafeicos/efeitos adversos , Ácidos Cafeicos/síntese química , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Álcool Feniletílico/efeitos adversos , Álcool Feniletílico/síntese química , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Coelhos
15.
Int J Pharm ; 470(1-2): 133-40, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24792979

RESUMO

Addition of one or more surfactant agents is often necessary for the production of nanostructured lipid and polymeric systems. The removal of residual surfactants is a required step for technological and toxicological reasons, especially for peculiar applications, such as the ophthalmic field. This study was planned to assess the technological properties of some surfactants, commonly used for the production of lipid nanoparticles, as well as their ocular safety profile. Stable and small-size solid lipid nanoparticles were obtained using Dynasan(®) 114 as the lipid matrix and all the tested surfactants. However, from a toxicological point of view, the nanocarriers produced using Kolliphor(®) P188 were the most valuable, showing no irritant effect on the ocular surface up to the highest tested surfactant concentration (0.4%, w/v). The SLN produced using Cremophor(®) A25 and Lipoid(®) S100 were tolerated up to a surfactant concentration of 0.2% by weight, while for Tween(®) 80 and Kolliphor(®) HS 15 a maximum concentration of 0.05% can be considered totally not-irritant.


Assuntos
Portadores de Fármacos/administração & dosagem , Olho/efeitos dos fármacos , Irritantes/administração & dosagem , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , Tensoativos/administração & dosagem , Animais , Portadores de Fármacos/química , Estabilidade de Medicamentos , Olho/patologia , Irritantes/química , Lipídeos/química , Masculino , Nanopartículas/química , Tamanho da Partícula , Coelhos , Tensoativos/química , Testes de Toxicidade Aguda
16.
J Pharm Pharmacol ; 66(7): 954-60, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24697218

RESUMO

OBJECTIVES: To evaluate the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) on retinal vascular leakage, and inflammatory markers in endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced in rats by lipopolysaccharide (LPS). Topical 0.5% indomethacin, 0.09% bromfenac and 0.1% nepafenac were given before and after LPS. Twenty-four hours after LPS, the animals were euthanized and plasma along with retina were collected to assess prostaglandin-E2 (PGE2 ) and C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay. Retinal vascular leakage was assessed by Evans blue. Molecular modelling was used to evaluate interaction of compounds with cyclooxygenase-2 (COX-2). KEY FINDINGS: All NSAIDs tested significantly prevented PGE2 production with higher effect of indomethacin and bromfenac in comparison with nepafenac. The three drugs did not affect plasma CRP levels. The analysis of retinal vascular leakage revealed a significant (P<0.01) decrease after treatment with indomethacin, but no significant changes were observed after treatment with bromfenac and nepafenac. Indomethacin had a different interaction with COX-2 in comparison with bromfenac and amfenac (active metabolite of nepafenac). CONCLUSIONS: Topical treatment with indomethacin, bromfenac and nepafenac has significant anti-inflammatory effects. However, only indomethacin was able to prevent retinal vascular leakage in LPS-injected rats, likely due to the distinctive molecular mechanism.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzenoacetamidas/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Indometacina/uso terapêutico , Inflamação/tratamento farmacológico , Fenilacetatos/uso terapêutico , Hemorragia Retiniana/prevenção & controle , Uveíte/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Benzenoacetamidas/administração & dosagem , Benzenoacetamidas/farmacologia , Benzofenonas/administração & dosagem , Benzofenonas/farmacologia , Bromobenzenos/administração & dosagem , Bromobenzenos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Indometacina/administração & dosagem , Indometacina/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Fenilacetatos/administração & dosagem , Fenilacetatos/farmacologia , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Uveíte/metabolismo
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