Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model

Chen, Mei; Li, Xiaoli; Liu, Jinkun; Yin, Hong; Cheng, Lingyun

doi:10.1016/j.jconrel.2015.02.021

Cited by 86 publications

(87 citation statements)

References 35 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Suprachoroidal delivery is being explored as a targeted ophthalmic drug delivery technique to treat posterior segment diseases that affect choroidal, retinal pigment epithelial, and/or retinal tissues (Chen et al, 2015; Einmahl et al, 2002; Gilger et al, 2013; Kadam et al, 2013; Olsen et al, 2006; Patel et al, 2012; Patel et al, 2011; Tyagi et al, 2012; Tzameret et al, 2014; Wang et al, 2012). The suprachoroidal space (SCS), which is a potential space between the sclera and choroid, is an attractive drug delivery site because it is directly adjacent to the diseased tissue in many posterior segment diseases, including age-related macular degeneration (AMD) and posterior uveitis (Ambati and Fowler, 2012; Gilger et al, 2013; Kim et al, 2014a).…”

Section: Introductionmentioning

confidence: 99%

Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries

Chiang

Kim

Edelhauser

et al. 2016

Experimental Eye Research

View full text Add to dashboard Cite

Microneedle injection into the suprachoroidal space (SCS) enables targeted drug delivery for treatment of posterior segment diseases (e.g., posterior uveitis). This study sought to identify and characterize anatomical barriers to circumferential spread of particles in the SCS of rabbit and human cadaver eyes. These barriers could make targeting specific regions within the SCS challenging. A hollow microneedle (33-gauge, 750 μm long) was used to inject fluorescent particles into albino New Zealand White rabbit eyes ex vivo at six different positions around the limbus and a limited number of conditions in vivo. SCS injections were also performed in human cadaver eyes 8 mm and 2 mm from the optic nerve (ON). Eyes were dissected and particle distribution was quantified. In rabbit eyes, injections made in the superior or inferior hemispheres (even when injected temporally immediately adjacent to the long posterior ciliary artery (LPCA)) did not significantly cross into the other hemisphere, apparently due to a barrier formed by the LPCA. The vortex veins had a minor effect on particle deposition, limited to only around the vortex vein root. In human eyes, the short posterior ciliary arteries (SPCAs) prevented circumferential spread towards the macula and ON. In conclusion, the rabbit LPCA and the human SPCA were anatomical barriers to particle spread within the SCS. Therefore, design of drug delivery protocols targeting the SCS need to account for barriers formed by anatomical structures in order for injected drug to reach target tissues.

show abstract

Section: Introductionmentioning

confidence: 99%

Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries

Chiang

Kim

Edelhauser

et al. 2016

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…This is because the microneedle used for injection inherently targets the supraciliary space due to its length and the injection procedure is almost identical to how current intravitreal injections are routinely performed, except for using a shorter needle. Studies in animals and humans have shown that microneedle injections into the suprachoroidal space have been well tolerated [26,27,35,38,48]. …”

Section: Discussionmentioning

confidence: 99%

“…The sclera and choroid are not tightly attached and thereby form a potential space that can be temporarily expanded without apparent long-term adverse effects [31,38,48,63–68]. Sustained-release formulations placed into the suprachoroidal space of animals and humans have been well tolerated [26,27,36,38].…”

Section: Discussionmentioning

confidence: 99%

Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma

Chiang

Kim

Doty

et al. 2016

Journal of Controlled Release

View full text Add to dashboard Cite

Although effective drugs that lower intraocular pressure (IOP) in the management of glaucoma exist, their efficacy is limited by poor patient adherence to the prescribed eye drop regimen. To replace the need for eye drops, in this study we tested the hypothesis that IOP can be reduced for one month after a single targeted injection using a microneedle for administration of a glaucoma medication (i.e., brimonidine) formulated for sustained release in the supraciliary space of the eye adjacent to the drug’s site of action at the ciliary body. To test this hypothesis, brimonidine-loaded microspheres were formulated using poly(lactic acid) (PLA) to release brimonidine at a constant rate for 35 days and microneedles were designed to penetrate through the sclera, without penetrating into the choroid/retina, in order to target injection into the supraciliary space. A single administration of these microspheres using a hollow microneedle was performed in the eye of New Zealand White rabbits and was found to reduce IOP initially by 6 mm Hg and then by progressively smaller amounts for more than one month. All administrations were well tolerated without significant adverse events, although histological examination showed a foreign-body reaction to the microspheres. This study demonstrates, for the first time, that the highly-targeted delivery of brimonidine-loaded microspheres into the supraciliary space using a microneedle is able to reduce IOP for one month as an alternative to daily eye drops.

show abstract

“…The suprachoroidal delivery of triamcinolone acetonide is a new mode of administration; it is considered to be safer than intravitreal injection and appears to overcome drug blockade at the sclera. [45] A single, unilateral, suprachoroidal injection of 40 mg/ml of CLS-TA after intravitreal injection of 2 mg of aflibercept will be compared with a suprachoroidal sham injection after intravitreal injection of 2 mg of aflibercept. The safety and efficacy will be monitored for 3 months.…”

Section: The Tanzanite Phase II Studymentioning

confidence: 99%

Investigational drugs for retinal vein occlusion

Bremond-Gignac

2016

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

show abstract

Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model

Cited by 86 publications

References 35 publications

Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries

Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries

Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma

Investigational drugs for retinal vein occlusion

Contact Info

Product

Resources

About