Photokinetic Drug Delivery: Light-Enhanced Permeation in an <i>In Vitro</i> Eye Model

Godley, Bernard F.; Kraft, E; Giannos, Steven A.; Zhao, Zhen-Yang; Haag, Anthony M.; Wen, Julie

doi:10.1089/jop.2015.0005

Cited by 2 publications

(4 citation statements)

References 25 publications

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“…Non-invasive transscleral drug delivery has been accomplished through iontophoresis, ( 26 – 28 ) sonophoresis ( 29 – 32 ) and photokinetics. ( 19 – 21 ) Eljarrat-Binstock et al . described the iontophoretic transscleral delivery of methotrexate in rabbit eyes.…”

Section: Discussionmentioning

confidence: 99%

“…The resulting cyclic physical shape change of the molecule and/or tissue may cause gross movement and result in the facilitated diffusion of the molecule into and through the sclera/cornea membrane. ( 21 , 24 )…”

Section: Discussionmentioning

confidence: 99%

“…( 19 ) This strategy was applied and investigated as a simplified model of scleral-vitreous interface and unstirred gel mimicking the vitreous. ( 21 )…”

Section: Introductionmentioning

confidence: 99%

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Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera

et al. 2018

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PurposePermeation studies, with near infrared (NIR) light and anti-aggregation antibody formulation, were used to investigate the in vitro permeation of bevacizumab, ranibizumab and aflibercept through human sclera.MethodsA vertical, spherical Franz cell diffusion apparatus was used for this scleral tissue permeation model. A photokinetic ocular drug delivery (PODD) testing device accommodated the placement of NIR LEDs above the donor chambers. An adjustable LED driver/square wave generator provided electrical energy with a variable pulse rate and pulse width modulation (duty cycle).ResultsExposure to non-thermal NIR light had no effect on mAbs with regard to monomer concentration or antibody binding potential, as determined by SE-HPLC and ELISA. The optimal LED wavelength was found to be 950 nm. Duty cycle power of 5% vs 20% showed no difference in permeation. When compared to controls, the combination of non-aggregating antibody formulation and NIR illumination provided an average transscleral drug flux enhancement factor of 3X.ConclusionNarrow wavelength incoherent (non-laser) light from an NIR LED source is not harmful to mAbs and can be used to enhance drug permeation through scleral tissue. The topical formulation, combined with pulsed NIR light irradiation, significantly improved scleral permeation of three anti-VEGF antibody drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera

et al. 2018

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“…Non-invasive or less invasive methods of drug delivery show promise, but also significant limitations [ 11 ]. Enhanced transscleral drug delivery has been accomplished through energy-based systems including iontophoresis [ 12 – 14 ] sonophoresis [ 15 – 18 ] and photokinetics [ 19 – 21 ]. Chemical and peptide based drug carrier permeation technologies are being explored [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Topical Solution for Retinal Delivery: Bevacizumab and Ranibizumab Eye Drops in Anti-Aggregation Formula (AAF) in Rabbits

Giannos,

Kraft,

Luisi

et al. 2024

Pharm Res

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Purpose Wet age-related macular degeneration (AMD) is a blinding retinal disease. Monthly intravitreal anti-VEGF antibody injections of bevacizumab (off-label) and ranibizumab (FDA approved) are the standard of care. Antibody aggregation may interfere with ocular absorption/distribution. This study assessed topical delivery of dilute antibodies to the posterior segment of rabbit eyes using a novel anti-aggregation formula (AAF). Methods Bevacizumab, or biosimilar ranibizumab was diluted to 5 mg/ml in AAF. All rabbits were dosed twice daily. Substudy 1 rabbits (bevacizumab, 100 µl eye drops): Group 1 (bevacizumab/AAF, n = 6); Group 2 (bevacizumab/PBS, n = 7) and Vehicle control (AAF, n = 1). Substudy 2 rabbits (ranibizumab biosimilar/AAF, 50 µl eye drops): (ranibizumab biosimilar/AAF, n = 8). At 14.5 days, serum was drawn from rabbits. Aqueous, vitreous and retina samples were recovered from eyes and placed into AAF aliquots. Tissue analyzed using AAF as diluent. Results Bevacizumab in AAF permeated/accumulated in rabbit aqueous, vitreous and retina 10 times more, than when diluted in PBS. AAF/0.1% hyaluronic acid eye drops, dosed twice daily, provided mean tissue concentrations (ng/g) in retina (29.50), aqueous (12.34), vitreous (3.46), and serum (0.28 ng/ml). Additionally, the highest concentration (ng/g) of ranibizumab biosimilar was present in the retina (18.0), followed by aqueous (7.82) and vitreous (1.47). Serum concentration was negligible (< 0.04 ng/ml). No irritation was observed throughout the studies. Conclusions Bevacizumab and ranibizumab, in an AAF diluent eye drop, can be delivered to the retina, by the twice daily dosing of a low concentration mAb formulation. This may prove to be an adjunct to intravitreal injections.

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Photokinetic Drug Delivery: Light-Enhanced Permeation in an In Vitro Eye Model

Abstract: The application of pulsed noncoherent visible light significantly enhances the permeation of MTX through a cross-linked collagen membrane and hyaluronic acid recipient medium without causing structural damage to the membrane.

Cited by 2 publications

References 25 publications

Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera

Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera

Topical Solution for Retinal Delivery: Bevacizumab and Ranibizumab Eye Drops in Anti-Aggregation Formula (AAF) in Rabbits

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