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Ocular barriers to retinal delivery of intravitreal liposomes : impact of vitreoretinal interface

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Abstract
Drug delivery to the posterior segment of the eye is challenging due to several anatomical and physiological barriers. Thus, there is a need for prolonged action and targeted drug delivery to treat retinal diseases. Intravitreal injections avoid anterior eye barriers, but the vitreoretinal interface and inner limiting membrane (ILM) may prevent access of drug delivery systems to the retina. Existing data on retinal permeation of intravitreal nanoparticles are sparse and probably misleading due to the inter-species differences of retinal structures in rodents and humans. To bridge this gap, retinal permeation of light-activated liposomes was studied in an ex vivo bovine explant system that simulates the structure of vitreoretinal interface and intact ILM. Our findings indicate that the particle size plays a significant role in determining the retinal penetration as the liposomes of >100 nm sized failed to overcome the ILM and could not permeate into the retina. In addition, our results demonstrate the impact of surface charge and PEG-coating on retinal penetration. Small (similar to 50 nm) anionic liposomes with PEG coating showed the most extensive distribution and cellular localization in the retina. In summary, this study extends understanding of ocular barriers, and provides valuable information to augment design of retinal drug delivery systems.
Keywords
INNER LIMITING MEMBRANE, CATIONIC LIPIDS, VITREOUS-HUMOR, DIFFUSION, NANOPARTICLES, MOVEMENT, CELLS, Liposomes, Intravitreal, Retinal permeation, Vitreoretinal interface, Inner limiting membrane, Animal models

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MLA
Tavakoli, Shirin, et al. “Ocular Barriers to Retinal Delivery of Intravitreal Liposomes : Impact of Vitreoretinal Interface.” JOURNAL OF CONTROLLED RELEASE, vol. 328, 2020, pp. 952–61, doi:10.1016/j.jconrel.2020.10.028.
APA
Tavakoli, S., Peynshaert, K., Lajunen, T., Devoldere, J., del Amo, E. M., Ruponen, M., … Urtti, A. (2020). Ocular barriers to retinal delivery of intravitreal liposomes : impact of vitreoretinal interface. JOURNAL OF CONTROLLED RELEASE, 328, 952–961. https://doi.org/10.1016/j.jconrel.2020.10.028
Chicago author-date
Tavakoli, Shirin, Karen Peynshaert, Tatu Lajunen, Joke Devoldere, Eva M. del Amo, Marika Ruponen, Stefaan De Smedt, Katrien Remaut, and Arto Urtti. 2020. “Ocular Barriers to Retinal Delivery of Intravitreal Liposomes : Impact of Vitreoretinal Interface.” JOURNAL OF CONTROLLED RELEASE 328: 952–61. https://doi.org/10.1016/j.jconrel.2020.10.028.
Chicago author-date (all authors)
Tavakoli, Shirin, Karen Peynshaert, Tatu Lajunen, Joke Devoldere, Eva M. del Amo, Marika Ruponen, Stefaan De Smedt, Katrien Remaut, and Arto Urtti. 2020. “Ocular Barriers to Retinal Delivery of Intravitreal Liposomes : Impact of Vitreoretinal Interface.” JOURNAL OF CONTROLLED RELEASE 328: 952–961. doi:10.1016/j.jconrel.2020.10.028.
Vancouver
1.
Tavakoli S, Peynshaert K, Lajunen T, Devoldere J, del Amo EM, Ruponen M, et al. Ocular barriers to retinal delivery of intravitreal liposomes : impact of vitreoretinal interface. JOURNAL OF CONTROLLED RELEASE. 2020;328:952–61.
IEEE
[1]
S. Tavakoli et al., “Ocular barriers to retinal delivery of intravitreal liposomes : impact of vitreoretinal interface,” JOURNAL OF CONTROLLED RELEASE, vol. 328, pp. 952–961, 2020.
@article{8697379,
  abstract     = {{Drug delivery to the posterior segment of the eye is challenging due to several anatomical and physiological barriers. Thus, there is a need for prolonged action and targeted drug delivery to treat retinal diseases. Intravitreal injections avoid anterior eye barriers, but the vitreoretinal interface and inner limiting membrane (ILM) may prevent access of drug delivery systems to the retina. Existing data on retinal permeation of intravitreal nanoparticles are sparse and probably misleading due to the inter-species differences of retinal structures in rodents and humans. To bridge this gap, retinal permeation of light-activated liposomes was studied in an ex vivo bovine explant system that simulates the structure of vitreoretinal interface and intact ILM. Our findings indicate that the particle size plays a significant role in determining the retinal penetration as the liposomes of >100 nm sized failed to overcome the ILM and could not permeate into the retina. In addition, our results demonstrate the impact of surface charge and PEG-coating on retinal penetration. Small (similar to 50 nm) anionic liposomes with PEG coating showed the most extensive distribution and cellular localization in the retina. In summary, this study extends understanding of ocular barriers, and provides valuable information to augment design of retinal drug delivery systems.}},
  author       = {{Tavakoli, Shirin and Peynshaert, Karen and Lajunen, Tatu and Devoldere, Joke and del Amo, Eva M. and Ruponen, Marika and De Smedt, Stefaan and Remaut, Katrien and Urtti, Arto}},
  issn         = {{0168-3659}},
  journal      = {{JOURNAL OF CONTROLLED RELEASE}},
  keywords     = {{INNER LIMITING MEMBRANE,CATIONIC LIPIDS,VITREOUS-HUMOR,DIFFUSION,NANOPARTICLES,MOVEMENT,CELLS,Liposomes,Intravitreal,Retinal permeation,Vitreoretinal interface,Inner limiting membrane,Animal models}},
  language     = {{eng}},
  pages        = {{952--961}},
  title        = {{Ocular barriers to retinal delivery of intravitreal liposomes : impact of vitreoretinal interface}},
  url          = {{http://doi.org/10.1016/j.jconrel.2020.10.028}},
  volume       = {{328}},
  year         = {{2020}},
}

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