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ICG-mediated photodisruption of the inner limiting membrane enhances retinal drug delivery

Karen Peynshaert (UGent) , Helena Vanluchene, Kaat De Clerck (UGent) , An-Katrien Minnaert, Morgane Verhoeven, Noémie Gouspillou (UGent) , Nezahat Bostan, Toshio Hisatomi, Geraldine Accou (UGent) , Félix Sauvage (UGent) , et al.
(2022) JOURNAL OF CONTROLLED RELEASE. 349. p.315-326
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Abstract
Many groundbreaking therapies for the treatment of blindness require delivery of biologics or cells to the inner retina by intravitreal injection. Unfortunately, the advancement of these therapies is greatly hampered by de-livery difficulties where obstruction of the therapeutics at the inner limiting membrane (ILM) represents the dominant bottleneck. In this proof-of-principle study, we explore an innovative light-based approach to locally ablate the ILM in a minimally invasive and highly controlled manner, thus making the ILM more permeable for therapeutics. More specifically, we demonstrate that pulsed laser irradiation of ILM-bound indocyanine green (ICG), a clinically applied ILM dye, results in the formation of vapor nanobubbles which can disrupt the bovine ILM as well as the extraordinary thick human ILM. We have observed that this photodisruption allows for highly successful retinal delivery of model nanoparticles which are otherwise blocked by the intact ILM. Strikingly, this treatment is furthermore able of enhancing the efficacy of mRNA-loaded lipid nanoparticles within the bovine retina by a factor of 5. In conclusion, this study provides evidence for a light-based approach to overcome the ILM which has the potential to improve the efficacy of all retinal therapies hampered by this delivery barrier.
Keywords
Pharmaceutical Science, Pulsed laser, Ophthalmology, Retinal drug delivery, Photodisruption, Lipid nanoparticles, Inner limiting membrane, Indocyanine green

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MLA
Peynshaert, Karen, et al. “ICG-Mediated Photodisruption of the Inner Limiting Membrane Enhances Retinal Drug Delivery.” JOURNAL OF CONTROLLED RELEASE, vol. 349, Elsevier BV, 2022, pp. 315–26, doi:10.1016/j.jconrel.2022.07.002.
APA
Peynshaert, K., Vanluchene, H., De Clerck, K., Minnaert, A.-K., Verhoeven, M., Gouspillou, N., … Remaut, K. (2022). ICG-mediated photodisruption of the inner limiting membrane enhances retinal drug delivery. JOURNAL OF CONTROLLED RELEASE, 349, 315–326. https://doi.org/10.1016/j.jconrel.2022.07.002
Chicago author-date
Peynshaert, Karen, Helena Vanluchene, Kaat De Clerck, An-Katrien Minnaert, Morgane Verhoeven, Noémie Gouspillou, Nezahat Bostan, et al. 2022. “ICG-Mediated Photodisruption of the Inner Limiting Membrane Enhances Retinal Drug Delivery.” JOURNAL OF CONTROLLED RELEASE 349: 315–26. https://doi.org/10.1016/j.jconrel.2022.07.002.
Chicago author-date (all authors)
Peynshaert, Karen, Helena Vanluchene, Kaat De Clerck, An-Katrien Minnaert, Morgane Verhoeven, Noémie Gouspillou, Nezahat Bostan, Toshio Hisatomi, Geraldine Accou, Félix Sauvage, Kevin Braeckmans, Stefaan De Smedt, and Katrien Remaut. 2022. “ICG-Mediated Photodisruption of the Inner Limiting Membrane Enhances Retinal Drug Delivery.” JOURNAL OF CONTROLLED RELEASE 349: 315–326. doi:10.1016/j.jconrel.2022.07.002.
Vancouver
1.
Peynshaert K, Vanluchene H, De Clerck K, Minnaert A-K, Verhoeven M, Gouspillou N, et al. ICG-mediated photodisruption of the inner limiting membrane enhances retinal drug delivery. JOURNAL OF CONTROLLED RELEASE. 2022;349:315–26.
IEEE
[1]
K. Peynshaert et al., “ICG-mediated photodisruption of the inner limiting membrane enhances retinal drug delivery,” JOURNAL OF CONTROLLED RELEASE, vol. 349, pp. 315–326, 2022.
@article{01GK1Q36Y364SXW9RS5ZEFQV6B,
  abstract     = {{Many groundbreaking therapies for the treatment of blindness require delivery of biologics or cells to the inner retina by intravitreal injection. Unfortunately, the advancement of these therapies is greatly hampered by de-livery difficulties where obstruction of the therapeutics at the inner limiting membrane (ILM) represents the dominant bottleneck. In this proof-of-principle study, we explore an innovative light-based approach to locally ablate the ILM in a minimally invasive and highly controlled manner, thus making the ILM more permeable for therapeutics. More specifically, we demonstrate that pulsed laser irradiation of ILM-bound indocyanine green (ICG), a clinically applied ILM dye, results in the formation of vapor nanobubbles which can disrupt the bovine ILM as well as the extraordinary thick human ILM. We have observed that this photodisruption allows for highly successful retinal delivery of model nanoparticles which are otherwise blocked by the intact ILM. Strikingly, this treatment is furthermore able of enhancing the efficacy of mRNA-loaded lipid nanoparticles within the bovine retina by a factor of 5. In conclusion, this study provides evidence for a light-based approach to overcome the ILM which has the potential to improve the efficacy of all retinal therapies hampered by this delivery barrier.}},
  author       = {{Peynshaert, Karen and Vanluchene, Helena and De Clerck, Kaat and Minnaert, An-Katrien and Verhoeven, Morgane and Gouspillou, Noémie and Bostan, Nezahat and Hisatomi, Toshio and Accou, Geraldine and Sauvage, Félix and Braeckmans, Kevin and De Smedt, Stefaan and Remaut, Katrien}},
  issn         = {{0168-3659}},
  journal      = {{JOURNAL OF CONTROLLED RELEASE}},
  keywords     = {{Pharmaceutical Science,Pulsed laser,Ophthalmology,Retinal drug delivery,Photodisruption,Lipid nanoparticles,Inner limiting membrane,Indocyanine green}},
  language     = {{eng}},
  pages        = {{315--326}},
  publisher    = {{Elsevier BV}},
  title        = {{ICG-mediated photodisruption of the inner limiting membrane enhances retinal drug delivery}},
  url          = {{http://doi.org/10.1016/j.jconrel.2022.07.002}},
  volume       = {{349}},
  year         = {{2022}},
}
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