Flt23k Nanoparticles Offer Additive Benefit in Graft Survival and Anti-Angiogenic Effects When Combined with Triamcinolone

Cho, Yang Kyung; Uehara, Hironori; Young, Jason R.; Tyagi, Puneet; Kompella, Uday B.; Zhang, Xiaohui; Luo, Ling; Singh, Nirbhai; Archer, Bonnie; Ambati, Balamurali K.

doi:10.1167/iovs.11-8393

Cited by 36 publications

(36 citation statements)

References 30 publications

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“…This result validated that albumin nanoparticles could prolong the expression of therapeutic plasmids. The effect of Flt23k in the form of poly L-lactideco-glycolide nanoparticles was tested by Cho et al 49 They performed this study in a murine cornea transplant model and found that subconjunctival injection of Flt23k poly L-lactideco-glycolide nanoparticle could reduce NV, lymphangiogenesis, and graft failure rate. In addition, combined Flt23k nanoparticle and steroid also elevated the 2-month graft survival rate significantly.…”

Section: Soluble or Modified Vegf Receptorsmentioning

confidence: 99%

Corneal neovascularization and contemporary antiangiogenic therapeutics

Hsu

Chang

Lin

et al. 2015

Journal of the Chinese Medical Association

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Corneal neovascularization (NV), the excessive ingrowth of blood vessels from conjunctiva into the cornea, is a common sequela of disease insult that can lead to visual impairment. Clinically, topical steroid, argon laser photocoagulation, and subconjunctival injection of bevacizumab have been used to treat corneal NV. Sometimes, the therapies are ineffective, especially when the vessels are large. Large vessels are difficult to occlude and easily recanalized. Scientists and physicians are now dedicated to overcoming this problem. In this article, we briefly introduce the pathogenesis of corneal NV, and then highlight the existing animal models used in corneal NV research-the alkali-induced model and the suture-induced model. Most of all, we review the potential therapeutic targets (i.e., vascular endothelial growth factor and platelet-derived growth factor) and their corresponding inhibitors, as well as the immunosuppressants that have been discovered in recent years by corneal NV studies.

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Section: Soluble or Modified Vegf Receptorsmentioning

confidence: 99%

Corneal neovascularization and contemporary antiangiogenic therapeutics

Hsu

Chang

Lin

et al. 2015

Journal of the Chinese Medical Association

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“…Growth Factor (VEGF) therapy, obtained both through corneal gene therapy and monoclonal antibody can significantly decrease corneal neovascularization and lymphangiogenesis, resulting in increased graft survival in keratoplasty [38].…”

Section: Iii)mentioning

confidence: 99%

Application of lipid nanoparticles to ocular drug delivery

Battaglia

Serpe

Foglietta

et al. 2016

Expert Opinion on Drug Delivery

122

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Although eye drops are widely used as drug delivery systems for the anterior segment of the eye, they are also associated with poor drug bioavailability due to transient contact time and rapid washout by tearing. Moreover, effective drug delivery to the posterior segment of the eye is challenging, and alternative routes of administration (periocular and intravitreal) are generally needed, the blood-retinal barrier being the major obstacle to systemic drug delivery. Areas covered: Nanotechnology, and especially lipid nanoparticles, can improve the therapeutic efficiency, compliance and safety of ocular drugs, administered via different routes, to both the anterior and posterior segment of the eye. This review highlights the main ocular barriers to drug delivery, as well as the most common eye diseases suitable for pharmacological treatment in which lipid nanoparticles have proved efficacious as alternative delivery systems. Expert opinion: Lipid-based nanocarriers are among the most biocompatible and versatile means for ocular delivery. Mucoadhesion with consequent increase in pre-corneal retention time, and enhanced permeation due to cellular uptake by corneal epithelial cells, are the essential goals for topical lipid nanoparticle delivery. Gene delivery to the retina has shown very promising results after intravitreal administration of lipid nanoparticles as non-viral vectors.

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“…194 In addition, a combination of Flt23k nanoparticles that deliver plasmids expressing anti-VEGF intrareceptor Flt23k and steroid treatment significantly reduces lymphangiogenesis and improves graft survival in a mouse model of corneal transplantation. 195 …”

Section: Diseases Associated With Corneal Lymphangiogenesismentioning

confidence: 99%

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

Yang

Walia

Huang

et al. 2016

Survey of Ophthalmology

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A major focus of cancer research for several decades has been understanding the ability of tumors to induce new blood vessel formation, a process known as angiogenesis. Unfortunately, only limited success has been achieved in the clinical application of angiogenesis inhibitors. We now know that lymphangiogenesis, the growth of lymphatic vessels, likely also plays a major role in tumor progression. Thus, therapeutic strategies targeting lymphangiogenesis or both lymphangiogenesis and angiogenesis may represent promising approaches for treating cancer and other diseases. Importantly, research progress toward understanding lymphangiogenesis is significantly behind that related to angiogenesis. A PubMed search of ‘angiogenesis’ returns nearly 80,000 articles, whereas a search of ‘lymphangiogenesis’ returns approximately 2,635 articles. This stark contrast can be explained by the lack of molecular markers for identifying the invisible lymphatic vasculature that persisted until less than two decades ago combined with the intensity of research interest in angiogenesis during the past half-century. Still, significant strides have been made in developing strategies to modulate lymphangiogenesis, largely using ocular disease models. Here, we review the current knowledge of lymphangiogenesis in the context of knockout models, ocular diseases, the biology of activators and inhibitors, and the potential for therapeutic interventions targeting this process.

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Flt23k Nanoparticles Offer Additive Benefit in Graft Survival and Anti-Angiogenic Effects When Combined with Triamcinolone

Abstract: Anti-VEGF nanoparticles (Flt23k) have a significant effect on decreasing neovascularization and lymphangiogenesis, resulting in increased graft survival in penetrating keratoplasty. This beneficial effect is synergistically enhanced with steroid treatment.

Cited by 36 publications

References 30 publications

Corneal neovascularization and contemporary antiangiogenic therapeutics

Corneal neovascularization and contemporary antiangiogenic therapeutics

Application of lipid nanoparticles to ocular drug delivery

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

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