Targeted Delivery of Antiglaucoma Drugs to the Supraciliary Space Using Microneedles

Kim, Yoo C.; Edelhauser, Henry F.; Prausnitz, Mark R.

doi:10.1167/iovs.14-14651

Cited by 72 publications

(66 citation statements)

References 50 publications

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“…Practices complied with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Although bioavailability and distribution of brimonidine is affected by the presence of pigment in the eye, albino rabbits were used to facilitate visualization of microspheres and since an albino rabbit animal model was used in a previous study [41,44]. The treatment groups are listed in the Table 2.…”

Section: Methodsmentioning

confidence: 99%

“…The baseline IOP was established by measuring IOP daily for a week prior to the injection. IOP was not taken on the day of injection because the ketamine cocktail used had a significant impact on IOP [37]. IOP was monitored on 1, 3, 5, 7, 10, 14, 17, 20, 24, 27, 30, 33, and 43 days post-injection.…”

Section: Methodsmentioning

confidence: 99%

“…Microneedle injections in the suprachoroidal space were originally designed as a treatment for posterior-segment diseases. This study seeks to treat glaucoma, which is an anterior-segment disease, by targeting drug delivery to the supraciliary space [37]. …”

Section: Introductionmentioning

confidence: 99%

“…In our initial study, a bolus microneedle injection of glaucoma drugs (including brimonidine) into the supraciliary space was able to reduce IOP with significant dose sparing compared with topical eye drops [37]. Furthermore, fewer ocular side effects are expected since the drug is compartmentalized in the suprachoroidal space away from other non-target tissues (e.g., lens, cornea).…”

Section: Introductionmentioning

confidence: 99%

“…Brimonidine was chosen because it is an FDA-approved IOP-lowering agent currently prescribed to glaucoma patients [12,13,40] and is pharmacologically active in the rabbit [19–22,41]. Due to increased bioavailability, a microneedle injection into the supraciliary space should reduce the dose needed, compared with topical eye drops, thereby allowing a relatively small injection to contain sufficient drug for extended therapy.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

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Rapidly Detachable Microneedles Using Porous Water‐Soluble Layer for Ocular Drug Delivery

Lee

Park

Kim

et al. 2020

Adv Materials Technologies

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Detachable microneedle (MN) technology is highly desired for treatment of ocular diseases such as keratitis or glaucoma because of its minimally invasiveness and sustained drug delivery. However, shortening of administration time during insertion into target tissues still remains an important issue, although various approaches using mechanical and chemical separation mechanisms have been attempted. Here, a rapidly detachable microneedle pen (RD‐MNP) containing a porous dissolvable sacrificial layer is fabricated for instant separation of the tip. The porous sacrificial layer is fabricated between a drug‐loaded tip and a base by freeze drying. The sacrificial layer is comprised of water soluble polymers: poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP). Porous structure can accelerate dissolution rate compared to solid structure due to its capillary effect that relies on pore size and distribution. The pore size and distribution of the sacrificial layer are controlled and detachment of an RD‐MNP with the optimum pore structures is immediate upon dipping the MNP in PBS. Furthermore, the insertion characteristics of the system are investigated using the gelatin phantom and porcine eye sclera. With the optimized sacrificial layer, a MN tip is almost immediately detached and embedded to the porcine sclera with the aid of impact insertion.

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Safety Assessment of Microneedle Technology for Transdermal Drug Delivery: A Review

Zhu

Zhang

et al. 2020

Advanced Therapeutics

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The promising development of the microneedle (MN) drug delivery system has prompted its clinical application as a substitute for traditional hypodermic injection needles. In addition to the satisfactory MN technology design for various application prospects, safety issues during MN use are increasingly an important consideration. This review aims to gather data from published literature regarding safety evaluations on MNs in relation to pain, skin irritation, in vivo degradation, as well as storage stability. By analyzing the existing testing methods and the safety performance of MNs, the description of MN safety is updated as painless, minimally invasive, and stable during storage. However, the development of MNs that can degrade in a human body should be addressed to accelerate clinical applications.

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Targeted Delivery of Antiglaucoma Drugs to the Supraciliary Space Using Microneedles

Cited by 72 publications

References 50 publications

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

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

Rapidly Detachable Microneedles Using Porous Water‐Soluble Layer for Ocular Drug Delivery

Safety Assessment of Microneedle Technology for Transdermal Drug Delivery: A Review

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