Ocular permeability, intraocular biodistribution of lipid nanocapsule formulation intended for retinal drug delivery.

Autor: Christensen G; Institute for Ophthalmic Research, University of Tübingen, Elfriede-Aulhorn Straße 5-7, 72076 Tübingen, Germany., Urimi D; Division Bioeconomy and Health, Chemical Process and Pharmaceutical Development, RISE Research Institutes of Sweden, Forskargatan 18, Södertälje 151 36, Sweden; Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, Reykjavík IS-107, Iceland., Lorenzo-Soler L; Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, Reykjavík IS-107, Iceland., Schipper N; Division Bioeconomy and Health, Chemical Process and Pharmaceutical Development, RISE Research Institutes of Sweden, Forskargatan 18, Södertälje 151 36, Sweden. Electronic address: nicolaas.schipper@ri.se., Paquet-Durand F; Institute for Ophthalmic Research, University of Tübingen, Elfriede-Aulhorn Straße 5-7, 72076 Tübingen, Germany. Electronic address: francois.paquet-durand@uni-tuebingen.de.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2023 Jun; Vol. 187, pp. 175-183. Date of Electronic Publication: 2023 Apr 22.
DOI: 10.1016/j.ejpb.2023.04.012
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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