Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development

Bansal, Pooja; Garg, Satpal; Sharma, Yograj; Venkatesh, Pradeep

doi:10.1089/jop.2015.0133

Cited by 43 publications

(35 citation statements)

References 64 publications

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“…Half-life extension of therapeutic proteins by binding to hyaluronan has advantages over other sustained delivery approaches such as biodegradable or non-biodegradable implants (Retisert, Ozurdex, Iluvien), encapsulated cell technology or implantable reserviors (ForSight, Replenish MicroPump), which require complicated manufacturing steps and surgical administration1617. A therapeutic protein fused to an hyaluronan-binding peptide is readily designed and manufactured and can be delivered by a simple intravitreal injection.…”

Section: Discussionmentioning

confidence: 99%

Long-acting protein drugs for the treatment of ocular diseases

et al. 2017

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Protein drugs that neutralize vascular endothelial growth factor (VEGF), such as aflibercept or ranibizumab, rescue vision in patients with retinal vascular diseases. Nonetheless, optimal visual outcomes require intraocular injections as frequently as every month. Here we report a method to extend the intravitreal half-life of protein drugs as an alternative to either encapsulation or chemical modifications with polymers. We combine a 97-amino-acid peptide of human origin that binds hyaluronan, a major macromolecular component of the eye's vitreous, with therapeutic antibodies and proteins. When administered to rabbit and monkey eyes, the half-life of the modified proteins is increased ∼3–4-fold relative to unmodified proteins. We further show that prototype long-acting anti-VEGF drugs (LAVAs) that include this peptide attenuate VEGF-induced retinal changes in animal models of neovascular retinal disease ∼3–4-fold longer than unmodified drugs. This approach has the potential to reduce the dosing frequency associated with retinal disease treatments.

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Section: Discussionmentioning

confidence: 99%

Long-acting protein drugs for the treatment of ocular diseases

et al. 2017

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“…[47–54] Procedure-related complications described include implant expulsion, implant migration, and wound dehiscence. [55]…”

Section: Introductionmentioning

confidence: 99%

“…It is injected into the eye in day care setting with a 25-gauge needle in the pars plana. [55] Once injected the microimplant continuously releases a low dose of FA into the vitreous (0.2μg/day FA) that lasts for up to 36 months. [65] Although it uses same drug matrix as Retisert®, it releases the drug at a lower dose (0.2 or 0.5μg/day versus 0.59μg/day with Retisert®).…”

Section: Introductionmentioning

confidence: 99%

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New Drugs and New Posterior Delivery Methods in CME

Dias

Nunes

Goldhardt

2017

Curr Ophthalmol Rep

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Purpose To discuss the characteristics, indications and adverse events (AEs) of sustained-release corticosteroid devices for the treatment of cystoid macular edema (CME). Recent findings Ozurdex® is approved for the treatment of diabetic macular edema (DME), retinal vein occlusion related-CME and noninfectious posterior uveitis (NIPU). It releases dexamethasone over a maximum period of 6 months making repeated intravitreal injections necessary for recurrent CME. Iluvien® releases fluocinolone for up to 36 months and is effective for the treatment of chronic DME. Retisert® (Bausch & Lomb, Rochester, NY) also releases fluocinolone, and is approved for chronic NIPU. Both Iluvien® and Retisert® are non-biodegradable devices and are highly associated with cataract and glaucoma. Summary Long-acting intraocular corticosteroid formulations offer a more predictable drug-release profile and reduced dosing frequency in comparison to conventional formulations of the same compounds but the risk-benefit ratio must be taken into consideration previous to the implantation of those devices.

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“…Inflammation of ocular posterior segment is often difficult to treat because of poor tissue permeability (Bourges et al, 2003;Bansal et al, 2016;Lajunen et al, 2016). Delivery of drug to the posterior segments is of great concern but also challenging due to the anatomical and physiological barriers of the eye and short drug duration.…”

Section: Introductionmentioning

confidence: 99%

Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit

Huang¹,

Liu

Yang

et al. 2017

Drug Delivery

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Corticosteroids have been used for treatment of posterior segment eye diseases, but the delivery of drug to the posterior segments is still a problem to resolve. In our study, we explore the feasibility of Sub-tenon's Controllable Continuous Drug Delivery to ocular posterior segment. Controllable continuous sub-tenon drug delivery (CCSDD) system, intravenous injections (IV) and sub-conjunctival injections (SC) were used to deliver dexamethasone disodium phosphate (DEXP) in rabbits, the dexamethasone concentration was measured in the ocular posterior segment tissue by Shimadzu LC-MS 2010 system at different time points in 24 h after first dose injection. Levels of dexamethasone were significantly higher at 12, 24 h in CCSDD than two other approaches, and at 3, 6 h in CCSDD than IV in vitreous body (p50.01); at 6, 12, 24 h in CCSDD than two other approaches, and at 1, 3 h in CCSDD than IV in retinal/ choroidal compound (p50.01); at 3, 6, 12, 24 h in CCSDD than two other approaches, and at 1 h in CCSDD than IV in sclera (p50.05). The AUC 0-24 in CCSDD group is higher than two other groups in all ocular posterior segment tissue. Our results demonstrated that dexamethasone concentration could be sustained moderately higher in the posterior segment by CCSDD than SC and IV, indicating that CCSDD might be a therapeutic alternative to treat a variety of intractable posterior segment diseases.

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Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development

Cited by 43 publications

References 64 publications

Long-acting protein drugs for the treatment of ocular diseases

Long-acting protein drugs for the treatment of ocular diseases

New Drugs and New Posterior Delivery Methods in CME

Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit

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