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  1 / 21552 MEDLINE  
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[PMID]:29173359
[Au] Autor:Al-Bayati I; Saadi M; Elhanafi S; McCallum RW
[Ad] Endereço:Department of Internal Medicine, Texas Tech University Health Sciences Center Paul L. Foster School of Medicine, El Paso, Texas.
[Ti] Título:Effectiveness of Bulking Agent (Solesta) Therapy in Fecal Incontinence in Patients Refractory to Conventional Therapies.
[So] Source:Am J Med Sci;354(5):476-479, 2017 11.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fecal incontinence is a problem that imposes considerable socioeconomic consequences. Despite many medical therapies, unmet needs remain. A new treatment option is a biocompatible bulking agent (Solesta) administered by submucosal injection in the distal rectum. The aims of this study are as follows: (1) To evaluate the efficacy and safety of this bulking agent in decreasing the severity of fecal incontinence (FI) and improving quality of life. (2) To obtain objective evidence of changes in anorectal physiology by high-resolution anorectal manometry pretreatment and posttreatment. MATERIALS AND METHODS: From January 2014 to June 2015, 17 patients who had failed medical therapy for FI received stabilized hyaluronate injected submucosally into the rectum under direct anoscopic visualization. The treatment was considered successful if patients achieved >50% reduction in FI events during monitoring for up to 12 months. RESULTS: After the first treatment session, 14 patients (82.3%) had a successful outcome. The remaining 3 patients received a second therapy 3 months later to achieve this result. At last follow-up, 7 of the 17 patients (41%) were having no FI events. The remaining patients had reduction in fecal accidents from a mean of 6.4/week baseline to 2.8/week during follow-up. CONCLUSIONS: Intrarectal injection of stabilized hyaluronate is effective for treating FI in patients who had failed standard medical treatments and is technically easy and safely performed as an outpatient procedure.
[Mh] Termos MeSH primário: Dextranos/administração & dosagem
Incontinência Fecal/tratamento farmacológico
Fármacos Gastrointestinais/administração & dosagem
Ácido Hialurônico/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Injeções Subcutâneas
Masculino
Meia-Idade
Reto
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dextrans); 0 (Gastrointestinal Agents); 0 (dextranomer-hyaluronic acid copolymer); 9004-61-9 (Hyaluronic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  2 / 21552 MEDLINE  
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[PMID]:29374708
[Au] Autor:Semkova S; Nikolova B; Zhelev Z; Tsoneva I; Zlateva G; Aoki I; Bakalova R
[Ad] Endereço:Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
[Ti] Título:Loading Efficiency of Polymersomes with Contrast Agents and their Intracellular Delivery: Quantum Dots Organic Dyes.
[So] Source:Anticancer Res;38(2):825-831, 2018 02.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Contrast nanocarriers as drug-delivery systems, capable of selective delivery to cancer cells and solid tumors, are essential for the development of new diagnostic and therapeutic (theranostic) strategies. The present study aimed to investigate the loading efficiency of chitosan-based polymersomes with fluorescent contrast substances [quantum dots (QDs) and conventional organic dyes] and the possibility to control their release from the polymer matrix into cells by chemical modifications and electroporation. MATERIALS AND METHODS: All investigated fluorophores were retained within the polymer globule via electrostatic and hydrophilic-hydrophobic interactions, without conjugation with the polymer. The fluorophore-loaded polymersomes were characterized by dynamic light scattering, zeta-potential titration, and fluorescence spectroscopy. The release of fluorophore from the polymersomes, passively or after electroporation, was detected by 5-step spin-ultrafiltration, combined with fluorescence spectroscopy of the upper phase (supernatant) of the filter unit. Passive intracellular delivery of the nanoparticles to HeLa cells was detected by fluorescence confocal microscopy. RESULTS: The QDs were retained tightly and continuously in the polymer matrix, while the organic fluorophores [fluorescein isothiocyanate (FITC), FITC-dextran and FITC-dextran ] were released rapidly from the polymersomes. The detergent Brij significantly increased the retention of FITC-dextran in the polymer globule. Electroporation up to 1000 V/cm did not induce release of QDs from the polymersomes, but accelerated the release of Brij-treated FITC-dextran B from the polymer matrix. High-voltage pulses (over 750 V/cm) induced also fragmentation or aggregation of the nanoparticles. QD_labeled polymersomes penetrated passively in cancer cells after 24-hour incubation. CONCLUSION: The results suggest that QD-labeled polymersomes are appropriate fluorescent probes and a nano-drug delivery system with high tracing opportunities for in vitro and in vivo applications. Furthermore, loading polymersomes with organic dyes with different molecular weights (such as FITC-dextrans) is a simple model for visualizing and predicting the rate of release of small organic molecules (e.g. conventional drugs, other contrasts, stabilizers, and supplements) from the polymer matrix.
[Mh] Termos MeSH primário: Meios de Contraste/administração & dosagem
Meios de Contraste/química
Corantes Fluorescentes/administração & dosagem
Corantes Fluorescentes/química
Pontos Quânticos/administração & dosagem
Pontos Quânticos/química
[Mh] Termos MeSH secundário: Quitosana/administração & dosagem
Quitosana/química
Meios de Contraste/farmacocinética
Dextranos/administração & dosagem
Dextranos/química
Sistemas de Liberação de Medicamentos
Fluoresceína-5-Isotiocianato/administração & dosagem
Fluoresceína-5-Isotiocianato/análogos & derivados
Fluoresceína-5-Isotiocianato/química
Células HeLa
Seres Humanos
Microscopia Confocal
Nanopartículas/administração & dosagem
Nanopartículas/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contrast Media); 0 (Dextrans); 0 (Fluorescent Dyes); 0 (fluorescein isothiocyanate dextran); 9012-76-4 (Chitosan); I223NX31W9 (Fluorescein-5-isothiocyanate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180129
[St] Status:MEDLINE


  3 / 21552 MEDLINE  
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[PMID]:28456983
[Au] Autor:Eriksson I; Öllinger K; Appelqvist H
[Ad] Endereço:Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, SE-58185, Linköping, Sweden.
[Ti] Título:Analysis of Lysosomal pH by Flow Cytometry Using FITC-Dextran Loaded Cells.
[So] Source:Methods Mol Biol;1594:179-189, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The acidic environment of the lysosomal lumen provides an optimal milieu for the acid hydrolases and is also essential for fusion/fission of endo-lysosomal compartments and sorting of cargo. Evidence suggests that maintaining lysosomal acidity is essential to avoid disease. In this chapter, we describe a protocol for analyzing the lysosomal pH in cultured cells using the fluorescent probe fluorescein isothiocyanate (FITC)-dextran together with a dual-emission ratiometric technique suitable for flow cytometry. Fluorescence-labeled dextran is endocytosed and accumulated in the lysosomal compartment. FITC shows a pH-dependent variation in fluorescence when analyzed at maximum emission wavelength and no variation when analyzing at the isosbestic point, thereby the ratio can be used to determine the lysosomal pH. A standard curve is obtained by equilibrating intralysosomal pH with extracellular pH using the ionophore nigericin. The protocol also includes information regarding procedures to induce lysosomal alkalinization and lysosomal membrane permeabilization.
[Mh] Termos MeSH primário: Dextranos/química
Fluoresceína-5-Isotiocianato/análogos & derivados
Lisossomos/metabolismo
[Mh] Termos MeSH secundário: Animais
Citometria de Fluxo
Fluoresceína-5-Isotiocianato/química
Seres Humanos
Concentração de Íons de Hidrogênio
Macrolídeos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dextrans); 0 (Macrolides); 0 (fluorescein isothiocyanate dextran); 116764-51-3 (bafilomycin A); I223NX31W9 (Fluorescein-5-isothiocyanate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_11


  4 / 21552 MEDLINE  
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[PMID]:29287079
[Au] Autor:Chou CY; Chang WI; Horng TL; Lin WL
[Ad] Endereço:Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan.
[Ti] Título:Numerical modeling of nanodrug distribution in tumors with heterogeneous vasculature.
[So] Source:PLoS One;12(12):e0189802, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The distribution and accumulation of nanoparticle dosage in a tumor are important in evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues.
[Mh] Termos MeSH primário: Antineoplásicos/farmacocinética
Portadores de Fármacos/administração & dosagem
Modelos Estatísticos
Nanopartículas
Neoplasias/irrigação sanguínea
[Mh] Termos MeSH secundário: Antineoplásicos/administração & dosagem
Dextranos/administração & dosagem
Doxorrubicina/administração & dosagem
Seres Humanos
Modelos Teóricos
Neoplasias/metabolismo
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Dextrans); 0 (Drug Carriers); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189802


  5 / 21552 MEDLINE  
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[PMID]:28452253
[Au] Autor:Khoshgard K; Kiani P; Haghparast A; Hosseinzadeh L; Eivazi MT
[Ad] Endereço:a Department of Medical Physics, Faculty of Medicine , Kermanshah University of Medical Sciences , Kermanshah , Iran.
[Ti] Título:Radiation dose rate affects the radiosensitization of MCF-7 and HeLa cell lines to X-rays induced by dextran-coated iron oxide nanoparticles.
[So] Source:Int J Radiat Biol;93(8):757-763, 2017 08.
[Is] ISSN:1362-3095
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced radiosensitivity by dextran-coated iron oxide in cancer cells. MATERIALS AND METHODS: HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations. RESULTS: Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 µg/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more radiosensitivity effect by increasing the dose rate and nanoparticles concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 µg/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively. CONCLUSION: Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the radiosensitization induced by the dextran-coated iron nanoparticles in these cells.
[Mh] Termos MeSH primário: Dextranos/química
Compostos Férricos/química
Compostos Férricos/farmacologia
Nanopartículas
Dose de Radiação
Radiossensibilizantes/química
Radiossensibilizantes/farmacologia
[Mh] Termos MeSH secundário: Relação Dose-Resposta à Radiação
Compostos Férricos/toxicidade
Células HeLa
Seres Humanos
Células MCF-7
Radiossensibilizantes/toxicidade
Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Dextrans); 0 (Ferric Compounds); 0 (Radiation-Sensitizing Agents); 1K09F3G675 (ferric oxide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180111
[Lr] Data última revisão:
180111
[Sb] Subgrupo de revista:IM; S
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1080/09553002.2017.1321806


  6 / 21552 MEDLINE  
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[PMID]:29252987
[Au] Autor:Kim S; Kim GH
[Ad] Endereço:Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea.
[Ti] Título:Roles of claudin-2, ZO-1 and occludin in leaky HK-2 cells.
[So] Source:PLoS One;12(12):e0189221, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Claudin-2, ZO-1, and occludin are major components of tight junctions (TJs) in the proximal tubule. However, their roles in maintaining paracellular permeability as leaky epithelia have yet to be defined. METHODS: To investigate the contributory role of TJ proteins in the leaky proximal tubule, we xamined the effect of inhibiting claudin-2, occludin, and ZO-1 expression on transepithelial electrical resistance (TER) and paracellular permeability using the immortalized human proximal tubule epithelial cell line HK-2. For this, small-interfering RNAs (siRNAs) against claudin-2, occludin and ZO-1 were transfected into HK-2 cells. TER and transepithelial flux rates of dextrans (4 and 70 kDa) were determined after 24 h. RESULTS: Transfection of siRNAs (25 nM) knocked down TJ protein expression. Control HK-2 monolayers achieved a steady-state TER of 6-8 Ω·cm2 when grown in 12-well Transwell filters, which are compatible with leaky epithelia. Knockdown of claudin-2 decreased in TER and increased occludin expression. Transfection with siRNA against either occludin or ZO-1 increased TER and decreased claudin-2 expression. TER was decreased by co-inhibition of claudin-2 and ZO-1 but increased by co-inhibition of claudin-2 and occludin. TER was suppressed when claudin-2, occludin, and ZO-1 were all inhibited. Dextran flux rate was increased by claudin-2, occludin, or ZO-1 siRNA transfection. Increased dextran flux was enhanced by co-transfection of claudin-2, ZO-1, and occludin siRNA. CONCLUSIONS: The depletion of claudin-2, occludin and ZO-1 in HK-2 cells had differential effects on TER and macromolecule flux. We demonstrated that integration of claudin-2, occludin and ZO-1 is necessary for maintaining the function of the proximal tubular epithelium.
[Mh] Termos MeSH primário: Claudina-2/metabolismo
Células Epiteliais/metabolismo
Ocludina/metabolismo
Proteína da Zônula de Oclusão-1/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Permeabilidade da Membrana Celular
Dextranos/metabolismo
Impedância Elétrica
Técnicas de Silenciamento de Genes
Seres Humanos
RNA Interferente Pequeno/metabolismo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Claudin-2); 0 (Dextrans); 0 (Occludin); 0 (RNA, Small Interfering); 0 (Zonula Occludens-1 Protein)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189221


  7 / 21552 MEDLINE  
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[PMID]:28450166
[Au] Autor:Wang Z; Gupta SK; Meenach SA
[Ad] Endereço:University of Rhode Island, College of Engineering, Department of Chemical Engineering, Kingston, RI 02881, USA.
[Ti] Título:Development and physicochemical characterization of acetalated dextran aerosol particle systems for deep lung delivery.
[So] Source:Int J Pharm;525(1):264-274, 2017 Jun 15.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Biocompatible, biodegradable polymers are commonly used as excipients to improve the drug delivery properties of aerosol formulations, in which acetalated dextran (Ac-Dex) exhibits promising potential as a polymer in various therapeutic applications. Despite this promise, there is no comprehensive study on the use of Ac-Dex as an excipient for dry powder aerosol formulations. In this study, we developed and characterized pulmonary drug delivery aerosol microparticle systems based on spray-dried Ac-Dex with capabilities of (1) delivering therapeutics to the deep lung, (2) targeting the particles to a desired location within the lungs, and (3) releasing the therapeutics in a controlled fashion. Two types of Ac-Dex, with either rapid or slow degradation rates, were synthesized. Nanocomposite microparticle (nCmP) and microparticle (MP) systems were successfully formulated using both kinds of Ac-Dex as excipients and curcumin as a model drug. The resulting MP were collapsed spheres approximately 1µm in diameter, while the nCmP were similar in size with wrinkled surfaces, and these systems dissociated into 200nm nanoparticles upon reconstitution in water. The drug release rates of the Ac-Dex particles were tuned by modifying the particle size and ratio of fast to slow degrading Ac-Dex. The pH of the environment was also a significant factor that influenced the drug release rate. All nCmP and MP systems exhibited desirable aerodynamic diameters that are suitable for deep lung delivery (e.g. below 5µm). Overall, the engineered Ac-Dex aerosol particle systems have the potential to provide targeted and effective delivery of therapeutics into the deep lung.
[Mh] Termos MeSH primário: Administração por Inalação
Aerossóis/química
Curcumina/administração & dosagem
Dextranos/química
[Mh] Termos MeSH secundário: Liberação Controlada de Fármacos
Excipientes/química
Pulmão/efeitos dos fármacos
Tamanho da Partícula
Pós
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aerosols); 0 (Dextrans); 0 (Excipients); 0 (Powders); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  8 / 21552 MEDLINE  
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[PMID]:28873542
[Au] Autor:Fan Y; Yi J; Zhang Y; Yokoyama W
[Ad] Endereço:College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China.
[Ti] Título:Fabrication of curcumin-loaded bovine serum albumin (BSA)-dextran nanoparticles and the cellular antioxidant activity.
[So] Source:Food Chem;239:1210-1218, 2018 Jan 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bovine serum albumin (BSA)-dextran conjugate was prepared with glycation. Self-assembly nanoparticles were synthesized with a green, and facile approach. The effects of dry-heating time on the fabrication and characteristics of BSA-dextran conjugate nanoparticles were examined. Stable nanoparticles (<200nm) were formed after only 6h dry-heating because enough dextran was grafted onto the BSA to provide significant steric hindrance. Particle size decreased with the increase of dry-heating time and the lowest particle size (51.2nm) was obtained after 24h dry-heating. The nanoparticles were stable in a wide pH range (pH 2.0-7.0). The particle size of nanoparticles increased to 115nm after curcumin incorporation and was stable even after one-month storage. TEM results demonstrated that curcumin-loaded nanoparticles displayed a spherical structure and were homogeneously dispersed. Curcumin in BSA-dextran nanoparticle showed better stability, compared to free curcumin. In addition, BSA-dextran nanoparticles can improve the cellular antioxidant activity of curcumin in Caco-2 cells.
[Mh] Termos MeSH primário: Nanopartículas
[Mh] Termos MeSH secundário: Células CACO-2
Curcumina
Dextranos
Seres Humanos
Soroalbumina Bovina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dextrans); 27432CM55Q (Serum Albumin, Bovine); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE


  9 / 21552 MEDLINE  
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[PMID]:28986592
[Au] Autor:Li H; Liu W; Sorenson CM; Sheibani N; Albert DM; Senanayake T; Vinogradov S; Henkin J; Zhang HF
[Ad] Endereço:Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, United States.
[Ti] Título:Sustaining Intravitreal Residence With L-Arginine Peptide-Conjugated Nanocarriers.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5142-5150, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (<50 nm in diameter) conjugated with cationic peptides containing L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous. Methods: We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week. Results: The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization. Conclusions: We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.
[Mh] Termos MeSH primário: Peptídeos Catiônicos Antimicrobianos/farmacocinética
Arginina/química
Ésteres do Colesterol/química
Dextranos/química
Portadores de Fármacos/farmacocinética
Corpo Vítreo/metabolismo
[Mh] Termos MeSH secundário: Animais
Peptídeos Catiônicos Antimicrobianos/química
Materiais Biocompatíveis
Portadores de Fármacos/química
Angiofluoresceinografia
Meia-Vida
Injeções Intravítreas
Nanopartículas
Ratos
Ratos Long-Evans
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimicrobial Cationic Peptides); 0 (Biocompatible Materials); 0 (Cholesterol Esters); 0 (Dextrans); 0 (Drug Carriers); 94ZLA3W45F (Arginine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171008
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22160


  10 / 21552 MEDLINE  
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[PMID]:28973323
[Au] Autor:Mathieu E; Gupta N; Ahari A; Zhou X; Hanna J; Yücel YH
[Ad] Endereço:Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
[Ti] Título:Evidence for Cerebrospinal Fluid Entry Into the Optic Nerve via a Glymphatic Pathway.
[So] Source:Invest Ophthalmol Vis Sci;58(11):4784-4791, 2017 Sep 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: The purpose of this study was to determine whether cerebrospinal fluid (CSF) enters the optic nerve via a glymphatic pathway and whether this entry is size-dependent. Methods: Fluorescent dextran tracers (fluorescein isothiocyanate [FITC]) of four different sizes (10, 40, 70, and 500 kDa) and FITC-ovalbumin (45 kDa) were injected into the CSF of 15 adult mice. Tracer distribution in the orbital optic nerve at 1 hour after injection was assessed in tissue sections with confocal microscopy. Tracer distribution within the optic nerve was studied in relation to blood vessels and astrocytes identified by isolectin histochemistry and glial fibrillary acidic protein (GFAP) immunofluorescence, respectively. Aquaporin 4 (AQP4) immunostaining was performed to assess astrocytic endfeet in relation to CSF tracer. Results: One hour following tracer injection into CSF, all tracer sizes (10-500 kDa) were noted in the subarachnoid space surrounding the orbital optic nerve. In all cases, 10 kDa (n = 4/4) and 40 kDa (n = 3/3) tracers were noted within the optic nerve, while 70-kDa tracer was occasionally noted (n = 1/4). Tracer found within the nerve was specifically localized between isolectin-labeled blood vessels and GFAP-positive astrocytes or AQP4-labeled astrocytic endfeet. The 500-kDa tracer was not detected within the optic nerve. Conclusions: To our knowledge, this is the first evidence of a glymphatic pathway in the optic nerve. CSF enters the optic nerve via spaces surrounding blood vessels, bordered by astrocytic endfeet. CSF entry into paravascular spaces of the optic nerve is size-dependent, and this pathway may be highly relevant to optic nerve diseases, including glaucoma.
[Mh] Termos MeSH primário: Líquido Cefalorraquidiano/fisiologia
Nervo Óptico
[Mh] Termos MeSH secundário: Animais
Astrócitos/metabolismo
Vasos Sanguíneos/metabolismo
Dextranos/farmacocinética
Modelos Animais de Doenças
Feminino
Fluoresceína-5-Isotiocianato/análogos & derivados
Fluoresceína-5-Isotiocianato/farmacocinética
Corantes Fluorescentes/farmacocinética
Masculino
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dextrans); 0 (Fluorescent Dyes); 0 (fluorescein isothiocyanate dextran); I223NX31W9 (Fluorescein-5-isothiocyanate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22290



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