Blood Retinal Barrier and Ocular Pharmacokinetics: Considerations for the Development of Oncology Drugs

2021 ◽  
Author(s):  
Beth Williamson ◽  
Venkatesh Pilla Reddy
Keyword(s):  
Ocular Pharmacokinetics ◽  
Blood Retinal Barrier

Nanoscale Drug Delivery Systems for Glaucoma: Experimental and In Silico Advances

2020 ◽  
Vol 20 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Ocular Drug Delivery ◽  
The Body ◽  
Single Wall Carbon Nanotubes ◽  
Blood Retinal Barrier ◽  
Novel Drugs ◽  
Blood Aqueous Barrier

: In this review nanoscale based drug delivery systems particularly in relevance to the antiglaucoma drugs have been discussed. In addition to that, the latest computational/in silico advances in this field are examined in brief. Using nanoscale materials for drug delivery, is an ideal option to target tumours and drug can be released at areas of the body where traditional drugs may fail to act. Nanoparticles, polymeric nanomaterials, single-wall carbon nanotubes (SWCNTs), quantum dots (QDs), liposomes and graphene are the most important nanomaterials used for drug delivery. Ocular drug delivery is one of the most common and difficult tasks faced by pharmaceutical scientists because of many challenges like circumventing the blood–retinal barrier, corneal epithelium and the blood–aqueous barrier. Authors found compelling empirical evidence of scientists relying on in-silico approaches to develop novel drugs and drug delivery systems for treating glaucoma. This review in nanoscale drug delivery systems will help us in understand the existing queries and evidence gaps and will pave way for effective design of novel ocular drug delivery systems

scholarly journals Influences of advanced glycosylation end products on the inner blood–retinal barrier in a co-culture cell model in vitro

2020 ◽  
Vol 15 (1) ◽  
pp. 619-628
Author(s):  
Chen Yuan ◽  
Ya Mo ◽  
Jie Yang ◽  
Mei Zhang ◽  
Xuejun Xie
Keyword(s):  
Electrical Resistance ◽  
Cell Model ◽  
Polyclonal Antibodies ◽  
Time Dependent ◽  
Dependent Manner ◽  
Blood Retinal Barrier ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Advanced Glycosylation

AbstractAdvanced glycosylation end products (AGEs) are harmful factors that can damage the inner blood–retinal barrier (iBRB). Rat retinal microvascular endothelial cells (RMECs) were isolated and cultured, and identified by anti-CD31 and von Willebrand factor polyclonal antibodies. Similarly, rat retinal Müller glial cells (RMGCs) were identified by H&E staining and with antibodies of glial fibrillary acidic protein and glutamine synthetase. The transepithelial electrical resistance (TEER) value was measured with a Millicell electrical resistance system to observe the leakage of the barrier. Transwell cell plates for co-culturing RMECs with RMGCs were used to construct an iBRB model, which was then tested with the addition of AGEs at final concentrations of 50 and 100 mg/L for 24, 48, and 72 h. AGEs in the in vitro iBRB model constructed by RMEC and RMGC co-culture led to the imbalance of the vascular endothelial growth factor (VEGF) and pigment epithelial derivative factor (PEDF), and the permeability of the RMEC layer increased because the TEER decreased in a dose- and time-dependent manner. AGEs increased VEGF but lowered PEDF in a dose- and time-dependent manner. The intervention with AGEs led to the change of the transendothelial resistance of the RMEC layer likely caused by the increased ratio of VEGF/PEDF.

scholarly journals Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 122 ◽  
Author(s):  
Rebekah Omarkhail Elliott ◽  
Mei He
Keyword(s):  
Drug Delivery ◽  
Traffic Control ◽  
Information Transfer ◽  
Cancer Metastasis ◽  
Research Field ◽  
Blood Retinal Barrier ◽  
Biological Barriers ◽  
Diagnostic Role ◽  
Delivery Platform ◽  
Traffic Control System

Since the 2013 Nobel Prize was awarded for the discovery of vesicle trafficking, a subgroup of nanovesicles called exosomes has been driving the research field to a new regime for understanding cellular communication. This exosome-dominated traffic control system has increased understanding of many diseases, including cancer metastasis, diabetes, and HIV. In addition to the important diagnostic role, exosomes are particularly attractive for drug delivery, due to their distinctive properties in cellular information transfer and uptake. Compared to viral and non-viral synthetic systems, the natural, cell-derived exosomes exhibit intrinsic payload and bioavailability. Most importantly, exosomes easily cross biological barriers, obstacles that continue to challenge other drug delivery nanoparticle systems. Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood–brain barrier (BBB), blood–cerebrospinal fluid barrier (BCSFB), blood–lymph barrier (BlyB), blood–air barrier (BAB), stromal barrier (SB), blood–labyrinth barrier (BLaB), blood–retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform. However, the systematic reviews summarizing such discoveries are still limited. This review covers state-of-the-art exosome research on crossing several important biological barriers with a focus on the current, accepted models used to explain the mechanisms of barrier crossing, including tight junctions. The potential to design and engineer exosomes to enhance delivery efficacy, leading to future applications in precision medicine and immunotherapy, is discussed.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

Experimental models of growth factor-mediated angiogenesis and blood–retinal barrier breakdown

2000 ◽  
Vol 35 (5) ◽  
pp. 233-239 ◽  
Author(s):  
Stanley A. Vinores ◽  
M.S. Seo ◽  
N. Okamoto ◽  
J.D. Ash ◽  
E.F. Wawrousek ◽  
...  
Keyword(s):  
Growth Factor ◽  
Experimental Models ◽  
Blood Retinal Barrier ◽  
Barrier Breakdown

scholarly journals Retinal Redox Stress and Remodeling in Cardiometabolic Syndrome and Diabetes

2010 ◽  
Vol 3 (6) ◽  
pp. 392-403 ◽  
Author(s):  
Ying Yang ◽  
Melvin R. Hayden ◽  
Susan Sowers ◽  
Sarika V. Bagree ◽  
James R. Sowers
Keyword(s):  
Metabolic Pathways ◽  
Tissue Injury ◽  
Disease Process ◽  
Polyol Pathway ◽  
The United States ◽  
Redox Stress ◽  
Blood Retinal Barrier ◽  
Cardiometabolic Syndrome ◽  
Hexosamine Pathway ◽  
Pathway Flux

Diabetic retinopathy (DR) is a significant cause of global blindness; a major cause of blindness in the United States in people aged between 20–74. There is emerging evidence that retinopathy is initiated and propagated by multiple metabolic toxicities associated with excess production of reactive oxygen species (ROS). The four traditional metabolic pathways involved in the development of DR include: increased polyol pathway flux, advanced glycation end-product formation, activation of protein kinase Cisoforms and hexosamine pathway flux. These pathways individually and synergisticallycontribute to redox stress with excess ROS resulting in retinal tissue injury resulting in significant microvascular blood retinal barrier remodeling. The toxicity of hyperinsulinemia, hyperglycemia, hypertension, dyslipidemia, increased cytokines and growth factors, in conjunction with redox stress, contribute to the development and progression of DR. Redox stress contributes to the development and progression of abnormalities of endothelial cells and pericytes in DR. This review focuses on the ultrastructural observations of the blood retinal barrier including the relationship between the endothelial cell and pericyte remodeling in young nine week old Zucker obese (fa/ fa) rat model of obesity; cardiometabolic syndrome, and the 20 week old alloxan induced diabetic porcine model. Preventing or delaying the blindness associated with these intersecting abnormal metabolic pathways may be approached through strategies targeted to reduction of tissue inflammation and oxidative—redox stress. Understanding these abnormal metabolic pathways and the accompanying redox stress and remodeling mayprovide both the clinician and researcher a new concept of approaching this complicated disease process

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