Controlled drug release from an ocular implant: an evaluation using dynamic three-dimensional magnetic resonance imaging

Author(s): Kim H, Robinson MR, Lizak MJ,Tansey G, Lutz RJ, et al.


purpose. The ability of an episcleral implant at the equator of the eye to deliver drugs to the posterior segment was evaluated, using a sustained-release implant containing gadolinium-DTPA (Gd-DTPA). The movement of this drug surrogate was assessed with magnetic resonance imaging (MRI) in the rabbit eye. The results were compared with a similar implant placed in the vitreous cavity through a scleral incision at the equator.

methods. Polymer-based implants releasing Gd-DTPA were manufactured and placed in the subconjunctival space on the episclera or in the vitreous cavity in live rabbit eyes (in vivo) and in freshly enucleated eyes (ex vivo). Release rates of implants in vitro were also determined. Dynamic three-dimensional MRI was performed using a 4.7-Tesla MRI system for 8 hours. MR images were developed and analyzed on computer.

results. Episcleral implants in vivo delivered a mean total of 2.7 μg Gd-DTPA into the vitreous, representing only 0.12% of the total amount of compound released from the implant in vitro. No Gd-DTPA was detected in the posterior segment of the eye. Ex vivo, the Gd-DTPA concentration in the vitreous was 30 times higher. In vivo eyes with intravitreal implants placed at the equator delivered Gd-DTPA throughout the vitreous cavity and posterior segment. Compartmental analysis of the ocular drug distribution from an episcleral implant showed that the elimination rate constant of Gd-DTPA from the subconjunctival space into the episcleral veins and conjunctival lymphatics was 3-log units higher than the transport rate constant for Gd-DTPA movement into the vitreous.

conclusions. In vivo, episcleral implants at the equator of the eye did not deliver a significant amount of Gd-DTPA into the vitreous, and no compound was identified in the posterior segment. A 30-fold increase in vitreous Gd-DTPA concentration occurred in the enucleated eyes, suggesting that there are significant barriers to the movement of drugs from the episcleral space into the vitreous in vivo. Dynamic three-dimensional MRI using Gd-DTPA, and possibly other contrast agents, may be useful in understanding the spatial relationships of ocular drug distribution and clearance mechanisms in the eye.

Advances in biomedical engineering and ocular surgical techniques have encouraged 

Similar Articles

Drug delivery to the posterior segment of the eye

Author(s): Lee TWY, RobinsonJR

Development andevaluation of prolonged release topical indomethacin formulations for ocularinflammation

Author(s): AdelliGR, Balguri SP, Punyamurthula N, Bhagav P, Majumdar S

Theblood-ocular barriers

Author(s): Cunha-Vaz J

Drug delivery to the retina: challenges and opportunities

Author(s): Duvvuri S,Majumdar S, Mitra AK

Ocularpreparations: the formulation approach

Author(s): Kaur IP, Kanwar M

Evaluation of topical hesperetin matrix filmfor back-of-the-eye delivery

Author(s): Adelli GR, Hingorani T, PunyamurthulaN, Balguri SP, Majumdar S

Ocular inserts - Advancement in therapy of eye diseases

Author(s): Kumari A, Sharma PK, Garg VK,Garg G

Ocular inserts for topical delivery

Author(s): SaettoneFM, Salminen L

Stability of benzocaine formulated in commercialoral disintegrating tablet platforms

Author(s): Köllmer M, Popescu C, Manda P,Zhou L, Gemeinhart RA

New methods of drug delivery

Author(s): Langer R

Iontophoretic drug delivery for the treatment ofscars

Author(s): Manda P, Angamuthu M, HiremathSR, Raman V, Murthy SN

Polysulfone capillary fiber forintraocular drug delivery: in vitro and in vivo evaluations

Author(s): Rahimy MH, PeymanGA, Chin SY, Golshani R, Aras C, et al.

Intravitreal sustained-releaseganciclovir

Author(s): Smith TJ, Pearson PA, BlandfordDL, Brown JD, Goins KA, et al.

Delivery of cefotaxime to the brain viaintranasal administration

Author(s): Manda P, Hargett JK, Kiran Vaka SR,Repka MA, Narasimha Murthy S

Biodegradable Intrascleral Implant for SustainedIntraocular Delivery of Betamethasone Phosphate

Author(s): Okabe J, Kimura H, Kunou N, OkabeK, Kato A, et al.

Delivery of ziconotide to cerebrospinalfluid via intranasal pathway for the treatment of chronic pain

Author(s): Manda P, Kushwaha AS, Kundu S,Shivakumar H, Jo SB, et al.

Episcleral implants for topotecandelivery to the posterior segment of the eye

Author(s): Carcaboso AM, Chiappetta DA,Opezzo JA, Höcht C, Fandiño AC, et al.