Passive and Oxymetazoline-Enhanced Delivery with a Lens Device: Pharmacokinetics and Efficacy Studies with Rabbits

Miller, David J.; Li, S. Kevin; Tuitupou, A. L.; Kochambilli, R. P.; Papangkorn, Kongnara; Mix, Donald; Higuchi, William I.; Higuchi, John W.

doi:10.1089/jop.2007.0116

Cited by 11 publications

(14 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The electrode device was made of silicone polymer and has a lens shaped design for application onto a rabbit eye (Miller et al, 2008). The device had three drug delivery chambers (about 2 mm apart).…”

Section: Methodsmentioning

confidence: 99%

Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

Molokhia

Jeong

Higuchi

et al. 2009

Experimental Eye Research

Self Cite

View full text Add to dashboard Cite

The distribution and clearance of macromolecules in ocular delivery are not well understood. It has been hypothesized that iontophoresis can enhance transscleral delivery of macromolecules. The objective of this study was to investigate the ocular distribution of a macromolecule after transscleral iontophoretic delivery and intravitreal injection in vivo using nuclear magnetic resonance imaging (MRI) and to compare these results. Experiments of constant current transscleral iontophoresis of 4 mA or intravitreal injection were performed on New Zealand white rabbits in vivo. Iontophoresis experiments were also performed on rabbits postmortem. Galbumin™ (Gd-labeled albumin) was the model permeant surrogate to clinical therapeutic agents. MRI was used to monitor the distribution of the molecule in the eye after ocular iontophoresis and intravitreal injection. In addition, the conjunctiva, sclera, choroid, and retina were extracted in the transscleral iontophoresis study to determine the amounts of Galbumin™ in these tissues using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The results show that iontophoresis enhanced the ocular delivery of Galbumin™. The macromolecule was mainly delivered into the conjunctiva and sclera in microgram quantities and then diffused towards the posterior section in the upper hemisphere of the eye in vivo. Both in vivo and postmortem studies show that the iontophoretic delivery of Galbumin™ into the vitreous was below the detection limit. In the intravitreal injection study, the diffusion coefficient of Galbumin™ in the vitreous humor was estimated to be close to that of free aqueous diffusion.

show abstract

Section: Methodsmentioning

confidence: 99%

Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

Molokhia

Jeong

Higuchi

et al. 2009

Experimental Eye Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…A remarkable increase was observed in local drug penetration with HLv implants compared with HL formulations, further supporting the relevance of a strategy to inhibit local vessels to reduce local clearance of the drug, as previously reported with ␣-adrenergic selective inhibitors such as oxymetazoline. 33 Plasma total TPT exposure in rabbits receiving HL and HLv implants was approximately three times lower than in rabbits receiving 1 mg drug either periocularly or intravenously. 16 Most interestingly, LTPT levels were low or undetectable in the implanted rabbits, whereas 30% and 40% of total TPT exposure in plasma was lactone in the rabbits that received periocular administration and IV administration, respectively.…”

Section: Discussionmentioning

confidence: 88%

Episcleral Implants for Topotecan Delivery to the Posterior Segment of the Eye

Carcaboso¹,

Chiappetta

Opezzo³

et al. 2010

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose. Intravenous or periocular topotecan has been proposed as new treatment modality for patients with advanced intraocular retinoblastoma, but systemic topotecan lactone exposure induced by both approaches may cause toxicity. The purpose of this study was to develop a topotecan-loaded ocular delivery system to minimize systemic exposure and achieve selective transscleral penetration. Methods. Biocompatible polymer implants containing low (0.3 mg) or high (2.3 mg) topotecan load were manufactured and characterized in vitro. Adrenaline (500 mug) was coloaded to induce local vasoconstriction in vivo in 2 of 4 animal groups. Implants were inserted into the episclera of rabbits, and topotecan (lactone and total) concentrations in ocular tissues and plasma were determined over a period of 48 hours. Results. In vitro, implants released 30% to 50% of the loaded drug within 48 hours and 45% to 70% by day 10. In vivo, topotecan lactone was highly accumulated in locally exposed ocular tissues (ranging from 10(5) to 10(6) ng/g in sclera and choroid and 10(2) to10(3) ng/g in retina) over 48 hours with all the formulations studied. Low vitreous topotecan lactone levels (approximately 5 ng/mL) were found in animals receiving concomitant local vasoconstriction and high load implants. Topotecan lactone concentrations in plasma and in contralateral eyes were minimal or undetectable as a marker of tissue selectivity of the proposed strategy. Conclusions. These studies may contribute to improving the efficacy and safety of chemotherapy treatments for retinoblastoma and may support the role of the local vasculature and tissues promoting drug clearance and local accumulation during transscleral drug delivery.

show abstract

“…85 Episcleral drug depot Another interesting ocular drug delivery device is an episcleral drug reservoir, also called an episcleral exoplant. 86 This device is an impermeable silicone drug reservoir that bypasses the episcleral clearance mechanism and therefore may allow unidirectional trans-scleral drug delivery to the eye. A solid or liquid can be placed into the reservoir, which therefore may accommodate various types of drugs.…”

Section: Suprachoroidal Drug Deliverymentioning

confidence: 99%

“…86 This device may provide a new approach for directed delivery of drugs to the retina, while minimizing the potential for systemic drug absorption. 86 However, long-term efficacy and tolerability need to be demonstrated.…”

Section: Suprachoroidal Drug Deliverymentioning

confidence: 99%

“…A solid or liquid can be placed into the reservoir, which therefore may accommodate various types of drugs. In one study in rabbits, fluorescein delivery to the retina and posterior vitreous was markedly higher than periocular injections of the same concentration of fluorescein, while at the same time there was a reduction in plasma levels of fluorescein with the exoplant compared to injection 86 . This device may provide a new approach for directed delivery of drugs to the retina, while minimizing the potential for systemic drug absorption 86 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Advancements in ocular drug delivery

Weiner

Gilger

2010

Veterinary Ophthalmology

View full text Add to dashboard Cite

This review covers both noninvasive and invasive ophthalmic drug delivery systems that can have application to therapy of veterinary ophthalmic diseases. Noninvasive approaches include gel technologies, permeation enhancement via pro-drug development, solubilization agents and nanoparticle technologies, iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and microdroplets. More invasive systems include both eroding implants and noneroding technologies that encompass diffusion based systems, active pumps, intraocular lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to addressing the physiologic challenges of achieving the necessary duration of delivery, tissue targeting and patient compliance, the commercial development factors of biocompatibility, sterilization, manufacturability and long-term stability will be discussed.

show abstract

Passive and Oxymetazoline-Enhanced Delivery with a Lens Device: Pharmacokinetics and Efficacy Studies with Rabbits

Cited by 11 publications

References 36 publications

Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

Episcleral Implants for Topotecan Delivery to the Posterior Segment of the Eye

Advancements in ocular drug delivery

Contact Info

Product

Resources

About