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Ocular permeability, intraocular biodistribution of lipid nanocapsule formulation intended for retinal drug delivery
University of Tübingen, Germany.
RISE Research Institutes of Sweden, Bioeconomy and Health, Chemical Process and Pharmaceutical Development. University of Iceland, Iceland.ORCID iD: 0000-0002-1463-4990
University of Iceland, Iceland.
RISE Research Institutes of Sweden, Bioeconomy and Health, Chemical Process and Pharmaceutical Development.ORCID iD: 0000-0003-3401-0728
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2023 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 187, p. 175-183Article in journal (Refereed) Published
Abstract [en]

Recently, cGMP analogues have been investigated for the treatment of inherited retinal degenerations (IRD) using intravitreal injections. However, higher vitreous elimination rates limit the possibility to treat the retina with small molecule drugs. Here, we investigated the potential of lipid nanocapsules (LNCs) as vehicles to reduce clearance and prolong the delivery of cGMP analogue, CN03 to the retinal photoreceptors. Initially LNCs were investigated for both topical/periocular and intravitreal administration routes. While LNC-mediated drug permeation through the cornea proved to be too low for clinical applications, intravitreal application showed significant promise. Intravitreally administered LNCs containing fluorescent tracer in ex vivo porcine eyes showed complete intravitreal dispersal within 24 h. Ocular bio-distribution on histological sections showed that around 10 % of the LNCs had reached the retina, and 40 % accumulated in the ciliary body. For comparison, we used fluorescently labeled liposomes and these showed a different intraocular distribution with 48 % accumulated in the retina, and almost none were in the ciliary body. LNCs were then tested in retinal explants prepared from wild-type (WT) and rd1 mouse. In WT retina LNCs showed no significant toxic effects up to a concentration of 5 mg/mL. In rd1 retina, the LNC/CN03 formulation protected rd1 photoreceptors with similar efficacy to that of free CN03, demonstrating the usefulness of LNC/CN03 formulation in the treatment of IRD. Overall, our results indicate the suitability of LNCs for intraocular administration and drug delivery to both the retina and the ciliary body. © 2023 The Author(s)

Place, publisher, year, edition, pages
Elsevier B.V. , 2023. Vol. 187, p. 175-183
Keywords [en]
Drug delivery, Explant cultures, Inherited retinal degenerations, Intravitreal injections, Lipid nanocapsules, Liposomes
National Category
Ophthalmology Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:ri:diva-64844DOI: 10.1016/j.ejpb.2023.04.012Scopus ID: 2-s2.0-85156267023OAI: oai:DiVA.org:ri-64844DiVA, id: diva2:1756937
Funder
EU, Horizon 2020, H2020-MSCA-ITN-2017-765441German Research Foundation (DFG), PA1751/10-1
Note

Funding details: European Commission, EC, H2020-MSCA-ITN-2017-765441; Funding details: Deutsche Forschungsgemeinschaft, DFG, PA1751/10-1; Funding text 1: This work was financially supported by the German Research Council (DFG; PA1751/10-1), and the European Union (transMed, H2020-MSCA-ITN-2017-765441), European Joint Programme on Rare Diseases - Joint Transnational Call 2020 (TreatRP).; 

Available from: 2023-05-15 Created: 2023-05-15 Last updated: 2023-05-26Bibliographically approved

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Urimi, DileepSchipper, Nicolaas

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