A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo

Galvin, Orla; Srivastava, Akshay; Kulkarni, Rajiv; Dykes, Steve; Vickers, Steven P.; Dickinson, Keith; Reynolds, Alison; Kilty, Claire; Redmond, Gareth; Jones, Rob; Cheetham, Sharon C.; Pandit, Abhay; Kennedy, Breandán N.

doi:10.1016/j.jconrel.2016.04.004

Cited by 28 publications

(20 citation statements)

References 66 publications

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“…Compared with Quininib (Q1)-The small molecule Q1 was previously identified to inhibit ocular angiogenesis in the zebrafish hyaloid vascular assay and tumor angiogenesis (22)(23)(24). Here, we sought to identify novel chemical entities with more potent antiangiogenic effects in vivo using the zebrafish intersegmental vessel assay.…”

Section: Analogues Have Enhanced Antiangiogenic Effects In Vivomentioning

confidence: 99%

“…Previous phenotype-based chemical screens discovered quininib (2-[(E)-2-(quinolin-2-yl)vinyl]phenol), a small quinoline molecule with novel antiangiogenic activity (22)(23)(24). Quininib antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT 1 and CysLT 2 ), does not target VEGF receptors, and inhibits phosphorylated ERK, a CysLT 1 downstream effector (22).…”

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confidence: 99%

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A Quininib Analogue and Cysteinyl Leukotriene Receptor Antagonist Inhibits Vascular Endothelial Growth Factor (VEGF)-independent Angiogenesis and Exerts an Additive Antiangiogenic Response with Bevacizumab

Butler

Reynolds

Tosetto

et al. 2017

Journal of Biological Chemistry

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Excess blood vessel growth contributes to the pathology of metastatic cancers and age-related retinopathies. Despite development of improved treatments, these conditions are associated with high economic costs and drug resistance. Bevacizumab (Avastin®), a monoclonal antibody against vascular endothelial growth factor (VEGF), is used clinically to treat certain types of metastatic cancers. Unfortunately, many patients do not respond or inevitably become resistant to bevacizumab, highlighting the need for more effective antiangiogenic drugs with novel mechanisms of action. Previous studies discovered quininib, an antiangiogenic small molecule antagonist of cysteinyl leukotriene receptors 1 and 2 (CysLT and CysLT). Here, we screened a series of quininib analogues and identified a more potent antiangiogenic novel chemical entity (IUPAC name ()-2-(2-quinolin-2-yl-vinyl)-benzene-1,4-diol HCl) hereafter designated Q8. Q8 inhibits developmental angiogenesis in Tg(:EGFP) zebrafish and inhibits human microvascular endothelial cell (HMEC-1) proliferation, tubule formation, and migration. Q8 elicits antiangiogenic effects in a VEGF-independent model of angiogenesis and exerts an additive antiangiogenic response with the anti-VEGF biologic bevacizumab. Cell-based receptor binding assays confirm that Q8 is a CysLT antagonist and is sufficient to reduce cellular levels of NF-κB and calpain-2 and secreted levels of the proangiogenic proteins intercellular adhesion molecule-1, vascular cell adhesion protein-1, and VEGF. Distinct reductions of VEGF by bevacizumab explain the additive antiangiogenic effects observed in combination with Q8. In summary, Q8 is a more effective antiangiogenic drug compared with quininib. The VEGF-independent activity coupled with the additive antiangiogenic response observed in combination with bevacizumab demonstrates that Q8 offers an alternative therapeutic strategy to combat resistance associated with conventional anti-VEGF therapies.

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Section: Analogues Have Enhanced Antiangiogenic Effects In Vivomentioning

confidence: 99%

mentioning

confidence: 99%

A Quininib Analogue and Cysteinyl Leukotriene Receptor Antagonist Inhibits Vascular Endothelial Growth Factor (VEGF)-independent Angiogenesis and Exerts an Additive Antiangiogenic Response with Bevacizumab

Butler

Reynolds

Tosetto

et al. 2017

Journal of Biological Chemistry

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“…Microneedles (MNs) are drug delivery devices which have rapidly developed in the last decade. These devices consist of very small needles capable of piercing tissue, creating micropaths through which drug molecules can permeate through [57][58][59] . The rapid development of these devices has shown the potential in enhanced intraocular drug delivery.…”

Section: Microneedlesmentioning

confidence: 99%

Approaches in Topical Ocular Drug Delivery and Developments in the Use of Contact Lenses As drug-delivery Devices

et al. 2017

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Drug-delivery approaches have diversified over the last two decades with the emergence of nanotechnologies, smart polymeric systems and multimodal functionalities. The intended target for specific treatment of disease is the key defining developing parameter. One such area which has undergone significant advancements relates to ocular delivery. This has been expedited by the development of material advancement, mechanistic concepts and through the deployment of advanced process technologies. This review will focus on the developments within lens-based drug delivery while touching on conventional and current methods of topical ocular drug delivery. A summary table will provide quick reference to note the key findings in this area. In addition, the review also elucidates current theranostic and diagnostic approaches based on ocular lenses.

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“…In addition to dissolving polymer, swellable microneedles were used as a drug pathway from the reservoir [114,115], as well as for increased mechanical strength [116], drug delivery [117], sustained release [118], and sample collecting [119,120]. Swellable microneedles are based on dissolvable microneedles from the preoperational point of view.…”

Section: Materials Shown Inmentioning

confidence: 99%

“…Swellable microneedles are based on dissolvable microneedles from the preoperational point of view. They are made of hydrolyzed poly(methylvinylether-co-maelic anhydride (11.1%) and poly(ethyleneglycol) [119,120] and crosslinked hyaluronic acid (HA) [116][117][118]. Matrix material has biocompatibility, and HA can be degraded by enzymatic degradation.…”

Section: Materials Shown Inmentioning

confidence: 99%

Considerations in the use of microneedles: pain, convenience, anxiety and safety

Jeong

Lee

Choi

et al. 2016

Journal of Drug Targeting

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Transdermal delivery using microneedles is gaining increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods. Microneedle products have recently become available on the market, and some of them are under evaluation for efficacy and safety. To be available in the market for cosmetic and therapeutic use, several factors should be considered, including pain, anxiety, convenience and safety. These factors are summarized and reviewed in this article according to type of microneedle. Various kinds of materials have been used for manufacturing microneedles and developing drug formulations for microneedles. Safety information about materials used for microneedles is summarized in terms of type of microneedles. In addition to their biocompatibility, mechanical safety is also discussed. This review can provide guidelines for designing microneedle products for proper use.

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A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo

Cited by 28 publications

References 66 publications

A Quininib Analogue and Cysteinyl Leukotriene Receptor Antagonist Inhibits Vascular Endothelial Growth Factor (VEGF)-independent Angiogenesis and Exerts an Additive Antiangiogenic Response with Bevacizumab

A Quininib Analogue and Cysteinyl Leukotriene Receptor Antagonist Inhibits Vascular Endothelial Growth Factor (VEGF)-independent Angiogenesis and Exerts an Additive Antiangiogenic Response with Bevacizumab

Approaches in Topical Ocular Drug Delivery and Developments in the Use of Contact Lenses As drug-delivery Devices

Considerations in the use of microneedles: pain, convenience, anxiety and safety

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