Sustained drug delivery in glaucoma

Knight, O'Rese J; Lawrence, Scott D.

doi:10.1097/icu.0000000000000031

Cited by 28 publications

(14 citation statements)

References 42 publications

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“…6,8 This is most likely due to poor treatment adherence, suggesting alternative therapeutic options or delivery systems that increase patient compliance could be beneficial. 10,13,15,19,20,24,25 We developed a series of NSs (Fig. 1) that encapsulate ocular hypotensive drugs to provide extended-release treatments that could minimize patient noncompliance.…”

Section: Discussionmentioning

confidence: 99%

“…52 Due to these challenges, more efficient drug delivery systems are being developed for ocular tissues that include ocular inserts, lipid-based nanocarriers, nanoparticles, and punctum inserts. 24,[49][50][51][52][53][54] Recent studies using topically applied nanoparticles loaded with ocular hypotensive drugs have shown promise. For example, topical administration of nanoparticles (256 nm) containing the carbonic anhydrase inhibitor methazolamide lowered IOP for 18 hours, with the maximal effect observed 2 to 8 hours after dosing.…”

Section: Discussionmentioning

confidence: 99%

“…Although more studies using our NS are required, we do feel the data presented here add to the growing body of work examining more effective ocular drug delivery methods for the treatment of diseases, like glaucoma and AMD. 24,[49][50][51][52][53][54] Compared to noncompliant patients, patients who adhere to treatment plans have lower ocular pressures, less disc cupping, and less visual field loss over time. 13 Given that glaucoma progresses to blindness, and this progression occurs faster with no treatment, one would think adherence rates for glaucoma therapy would be quite high.…”

Section: Discussionmentioning

confidence: 99%

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Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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Purpose: We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice.Methods: Bilateral ocular hypertension was induced in mice by injecting microbeads into the anterior chamber. Hypertensive mice received NS loaded with ocular hypotensive drugs via intravitreal injection and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using confocal microscopy.Results: Brimonidine-loaded NS lowered IOP 12% to 30% for up to 6 days (P , 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4 days (P , 0.02) compared to saline injection. Three bimatoprost NS were tested: a 400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC-NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and 18% to 26%, respectively, for up to 32 days (P , 0.046). Over time retinal deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was internalized by RGCs.Conclusions: A single injection of NS can effectively deliver ocular hypotensive drugs in a linear and continuous manner for up to 32 days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in glaucoma.Translational Relevance: Patient compliance is a major issue in glaucoma. The use of NS to deliver a controlled, sustained release of therapeutics could drastically reduce the number of patients that progress to vision loss in this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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“…A full description of these technologies is beyond the scope of this article, but the reader is referred to a recent in-depth review of this topic. 112 Obviously such sustained release methods may reduce the problem of a patient's adherence to prescribed medication, improve bioavailability of the drug, and reduce side effects at the ocular surface. There are, however, still issues with sustained release systems, including safety and tolerability related partially to erratic drug release and final burst release.…”

Section: Systemic Therapiesmentioning

confidence: 99%

Pharmacotherapy of Glaucoma

Schmidl

Schmetterer²,

Garhöfer³

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

136

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Glaucoma is a group of diseases involving the optic nerve and associated structures, which is characterized by progressive visual field loss and typical changes of the optic nerve head (ONH). The only known treatment of the disease is reduction of intraocular pressure (IOP), which has been shown to reduce glaucoma progression in a variety of large-scale clinical trials. Nowadays, a relatively wide array of topical antiglaucoma drugs is available, including prostaglandin analogues, carbonic anhydrase inhibitors, beta-receptor antagonists, adrenergic agonists, and parasympathomimetics. In clinical routine, this allows for individualized treatment taking risk factors, efficacy, and safety into account. A major challenge is related to adherence to therapy. Sustained release devices may help minimize this problem but are not yet available for clinical routine use. Another hope arises from non-IOP-related treatment concepts. In recent years, much knowledge has been gained regarding the molecular mechanisms that underlie the disease process in glaucoma. This also strengthens the hope that glaucoma therapy beyond IOP lowering will become available. Implementing this concept with clinical trials remains, however, a challenge.

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“…101 In animal models, researchers have been able to safely deliver prostaglandins and alphaagonist agents to the supraciliary space leading to significant IOP lowering and allowing multiple-dose sparing (up to 100-fold). 102 In another study, prostaglandin-loaded inserts were administered into the conjunctival sac of rats and resulted in significant IOP lowering with decreased RGC loss compared to controls.…”

Section: Difficulties In Evaluating the Rate Of Progressionmentioning

confidence: 99%