Evaluating in vivo delivery of riboflavin with Coulomb- controlled iontophoresis for corneal collagen cross- linking: A pilot study

Alejandro Arboleda, Laura Kowalczuk, Michéle Savoldelli, Christophe Klein, Sophia Ladraa, Marie Christine Naud, Mariela C. Aguilar, Jean-Marie A Parel, Francine Behar-Cohen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose. To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for delivery of riboflavin prior to corneal collagen cross-linking (CXL). Methods. The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20 eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate the in vivo delivery of two riboflavin solutions: 0.1% riboflavin-20% dextran T500 solution (riboflavindextran) and 0.1% riboflavin 5′-phosphate (riboflavin-phosphate). After systemic intramuscular anesthesia, 0.25 mL of the photosensitizing agent was delivered by either instillation or CCI (2.11 mA/cm2 for 4 or 10 minutes) into either epithelial condition. The CCI probe on the eye without current served as control. Confocal microscopy of flat-mounted corneas was used to analyze intracorneal penetration and fluorometry was used to quantify riboflavin in the aqueous within 30 minutes of treatment. RESULTS. Instillation and CCI allowed for uniform delivery of riboflavin-dextran throughout the stroma after epithelial debridement. Transepithelial delivery of riboflavin-dextran was not efficacious. Riboflavin-phosphate was successfully delivered in both epithelium conditions. Complete saturation of the cornea was achieved using CCI after removing the epithelium, the epi-ON case allowed for limited diffusion. Increasing the time from 4 to 10 minutes greatly increased the amount of riboflavin detected in the cornea and aqueous humor. Conclusions. Coulomb-controlled iontophoresis is an effective technique for transepithelial delivery of riboflavin-phosphate into the cornea. This drug delivery method would allow clinicians to significantly shorten the time required for the CXL procedure, with or without epithelial debridement. Whether efficient crosslinking can be achieved through an intact epithelium remains to be demonstrated.

Original languageEnglish
Pages (from-to)2731-2738
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number4
DOIs
StatePublished - Mar 25 2014

Fingerprint

Iontophoresis
Riboflavin
Collagen
Epithelium
Cornea
Dextrans
Phosphates
Debridement
Flavin Mononucleotide
Fluorometry
Photosensitizing Agents
Aqueous Humor
Confocal Microscopy
Anesthesia

Keywords

  • Collagen cross-linking
  • Drug delivery
  • Iontophoresis
  • Keratoconus
  • Riboflavin

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Evaluating in vivo delivery of riboflavin with Coulomb- controlled iontophoresis for corneal collagen cross- linking : A pilot study. / Arboleda, Alejandro; Kowalczuk, Laura; Savoldelli, Michéle; Klein, Christophe; Ladraa, Sophia; Naud, Marie Christine; Aguilar, Mariela C.; Parel, Jean-Marie A; Behar-Cohen, Francine.

In: Investigative Ophthalmology and Visual Science, Vol. 55, No. 4, 25.03.2014, p. 2731-2738.

Research output: Contribution to journalArticle

Arboleda, Alejandro ; Kowalczuk, Laura ; Savoldelli, Michéle ; Klein, Christophe ; Ladraa, Sophia ; Naud, Marie Christine ; Aguilar, Mariela C. ; Parel, Jean-Marie A ; Behar-Cohen, Francine. / Evaluating in vivo delivery of riboflavin with Coulomb- controlled iontophoresis for corneal collagen cross- linking : A pilot study. In: Investigative Ophthalmology and Visual Science. 2014 ; Vol. 55, No. 4. pp. 2731-2738.
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abstract = "Purpose. To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for delivery of riboflavin prior to corneal collagen cross-linking (CXL). Methods. The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20 eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate the in vivo delivery of two riboflavin solutions: 0.1{\%} riboflavin-20{\%} dextran T500 solution (riboflavindextran) and 0.1{\%} riboflavin 5′-phosphate (riboflavin-phosphate). After systemic intramuscular anesthesia, 0.25 mL of the photosensitizing agent was delivered by either instillation or CCI (2.11 mA/cm2 for 4 or 10 minutes) into either epithelial condition. The CCI probe on the eye without current served as control. Confocal microscopy of flat-mounted corneas was used to analyze intracorneal penetration and fluorometry was used to quantify riboflavin in the aqueous within 30 minutes of treatment. RESULTS. Instillation and CCI allowed for uniform delivery of riboflavin-dextran throughout the stroma after epithelial debridement. Transepithelial delivery of riboflavin-dextran was not efficacious. Riboflavin-phosphate was successfully delivered in both epithelium conditions. Complete saturation of the cornea was achieved using CCI after removing the epithelium, the epi-ON case allowed for limited diffusion. Increasing the time from 4 to 10 minutes greatly increased the amount of riboflavin detected in the cornea and aqueous humor. Conclusions. Coulomb-controlled iontophoresis is an effective technique for transepithelial delivery of riboflavin-phosphate into the cornea. This drug delivery method would allow clinicians to significantly shorten the time required for the CXL procedure, with or without epithelial debridement. Whether efficient crosslinking can be achieved through an intact epithelium remains to be demonstrated.",
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AU - Arboleda, Alejandro

AU - Kowalczuk, Laura

AU - Savoldelli, Michéle

AU - Klein, Christophe

AU - Ladraa, Sophia

AU - Naud, Marie Christine

AU - Aguilar, Mariela C.

AU - Parel, Jean-Marie A

AU - Behar-Cohen, Francine

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N2 - Purpose. To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for delivery of riboflavin prior to corneal collagen cross-linking (CXL). Methods. The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20 eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate the in vivo delivery of two riboflavin solutions: 0.1% riboflavin-20% dextran T500 solution (riboflavindextran) and 0.1% riboflavin 5′-phosphate (riboflavin-phosphate). After systemic intramuscular anesthesia, 0.25 mL of the photosensitizing agent was delivered by either instillation or CCI (2.11 mA/cm2 for 4 or 10 minutes) into either epithelial condition. The CCI probe on the eye without current served as control. Confocal microscopy of flat-mounted corneas was used to analyze intracorneal penetration and fluorometry was used to quantify riboflavin in the aqueous within 30 minutes of treatment. RESULTS. Instillation and CCI allowed for uniform delivery of riboflavin-dextran throughout the stroma after epithelial debridement. Transepithelial delivery of riboflavin-dextran was not efficacious. Riboflavin-phosphate was successfully delivered in both epithelium conditions. Complete saturation of the cornea was achieved using CCI after removing the epithelium, the epi-ON case allowed for limited diffusion. Increasing the time from 4 to 10 minutes greatly increased the amount of riboflavin detected in the cornea and aqueous humor. Conclusions. Coulomb-controlled iontophoresis is an effective technique for transepithelial delivery of riboflavin-phosphate into the cornea. This drug delivery method would allow clinicians to significantly shorten the time required for the CXL procedure, with or without epithelial debridement. Whether efficient crosslinking can be achieved through an intact epithelium remains to be demonstrated.

AB - Purpose. To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for delivery of riboflavin prior to corneal collagen cross-linking (CXL). Methods. The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20 eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate the in vivo delivery of two riboflavin solutions: 0.1% riboflavin-20% dextran T500 solution (riboflavindextran) and 0.1% riboflavin 5′-phosphate (riboflavin-phosphate). After systemic intramuscular anesthesia, 0.25 mL of the photosensitizing agent was delivered by either instillation or CCI (2.11 mA/cm2 for 4 or 10 minutes) into either epithelial condition. The CCI probe on the eye without current served as control. Confocal microscopy of flat-mounted corneas was used to analyze intracorneal penetration and fluorometry was used to quantify riboflavin in the aqueous within 30 minutes of treatment. RESULTS. Instillation and CCI allowed for uniform delivery of riboflavin-dextran throughout the stroma after epithelial debridement. Transepithelial delivery of riboflavin-dextran was not efficacious. Riboflavin-phosphate was successfully delivered in both epithelium conditions. Complete saturation of the cornea was achieved using CCI after removing the epithelium, the epi-ON case allowed for limited diffusion. Increasing the time from 4 to 10 minutes greatly increased the amount of riboflavin detected in the cornea and aqueous humor. Conclusions. Coulomb-controlled iontophoresis is an effective technique for transepithelial delivery of riboflavin-phosphate into the cornea. This drug delivery method would allow clinicians to significantly shorten the time required for the CXL procedure, with or without epithelial debridement. Whether efficient crosslinking can be achieved through an intact epithelium remains to be demonstrated.

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KW - Iontophoresis

KW - Keratoconus

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