Clinical Evaluation of Pazopanib Eye Drops in Healthy Subjects and in Subjects With Neovascular Age-Related Macular Degeneration

Singh, Rishi P.; Wurzelmann, John I.; Li, Ye; Henderson, Linda S.; Hossain, Mohammad; Trivedi, Trupti; Kelly, Deborah S.

doi:10.1097/iae.0000000000000179

Cited by 21 publications

(12 citation statements)

References 22 publications

(31 reference statements)

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“…Pazopanib is another small-molecule multikinase inhibitor which was administered topically in a laser-induced CNV rat model (Yafai et al, 2011). Similar to TG100801, pazopanib failed to demonstrate efficacy in patients with subfoveal CNV, secondary to AMD (Singh et al, 2014). Along similar lines, acrizanib was investigated for reduction of nonvascular AMD in preclinical mouse models.…”

Section: Noninvasive Drug-delivery Systems For the Posterior Disordersmentioning

confidence: 99%

Ocular Drug Delivery: Present Innovations and Future Challenges

Gote

Sikder

Sicotte

et al. 2019

J Pharmacol Exp Ther

289

209

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Ocular drug delivery has always been a challenge for ophthalmologists and drug-delivery scientists due to the presence of various anatomic and physiologic barriers. Inimitable static and dynamic ocular barriers not only exclude the entry of xenobiotics but also discourage the active absorption of therapeutic agents. Designing an ideal delivery scheme should include enhanced drug bioavailability and controlled release of drug at the site of action, which can overcome various ocular barriers. Conventional ophthalmic medications include the use of topical eye drops and intravitreal injections of anti-vascular endothelial growth factor agent for treatment of anterior and posterior segment disorders, respectively. Current inventions for anterior ocular segment disorders such as punctum plugs, ocular implants, drug-eluting contact lenses, and ocular iontophoresis represent state-of-the-art inventions for sustained and controlled drug release. Parallel efforts for ocular drug delivery technologies for back of the eye disorders have resulted in the approval of various intravitreal implants. Novel drug-delivery technologies, including nanoparticles, nanomicelles, dendrimers, microneedles, liposomes, and nanowafers, are increasingly studied for anterior and posterior disorders. To achieve patient compliance for back of the eye disorders, novel approaches for noninvasive delivery of potent therapeutic agents are on the rise. In this review article, we discuss past successes, present inventions, and future challenges in ocular drug-delivery technologies. This expert opinion also discusses the future challenges for ocular drug-delivery systems and the clinical translatable potential of nanotechnology from benchtop to bedside.

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Section: Noninvasive Drug-delivery Systems For the Posterior Disordersmentioning

confidence: 99%

Ocular Drug Delivery: Present Innovations and Future Challenges

Gote

Sikder

Sicotte

et al. 2019

J Pharmacol Exp Ther

289

209

View full text Add to dashboard Cite

show abstract

“…Among 3 trials (16.7%) that reported receiving funding for their research, 2 trials [ 11 , 25 ] were supported by the government and 1 by the pharmaceutical industry. [ 26 ] No financial conflicts of interest were declared in 5 trials (27.8%).…”

Section: Resultsmentioning

confidence: 99%

Safety of antivascular endothelial growth factor administration in the ocular anterior segment in pterygium and neovascular glaucoma treatment

et al. 2018

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“…Typically, only 40–60% of patients adhere to glaucoma drop therapy regimens, even in cases where the patients know they are being monitored and were provided free medication [ 13 , 14 , 15 ]. Furthermore, achieving effective drug delivery to the posterior segment with an eye drop is challenging [ 16 , 17 , 18 , 19 ]. The most common approach for achieving drug delivery to the posterior segment is intravitreal (IVT) injection, which is employed every 6–8 weeks to deliver biologics for treatment of wet age-related macular degeneration [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

et al. 2021

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Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

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Clinical Evaluation of Pazopanib Eye Drops in Healthy Subjects and in Subjects With Neovascular Age-Related Macular Degeneration

Abstract: Pazopanib was well tolerated. In subjects with previously untreated neovascular age-related macular degeneration, pazopanib instilled 4 times daily as monothereapy did not seem to improve the best-corrected visual acuity or decrease the central retinal thickness.

Cited by 21 publications

References 22 publications

Ocular Drug Delivery: Present Innovations and Future Challenges

Ocular Drug Delivery: Present Innovations and Future Challenges

Safety of antivascular endothelial growth factor administration in the ocular anterior segment in pterygium and neovascular glaucoma treatment

Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

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