Badr, Moutaz Y;
Halwani, Abdulrahman A;
Odunze, Uchechukwu;
Eskandarpour, Malihe;
Calder, Virginia L;
Schätzlein, Andreas G;
Uchegbu, Ijeoma F;
(2022)
The Topical Ocular Delivery of Rapamycin to Posterior Eye Tissues and the Suppression of Retinal Inflammatory Disease.
International Journal of Pharmaceutics
, 621
, Article 121755. 10.1016/j.ijpharm.2022.121755.
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Abstract
Treatment of posterior eye diseases with intravitreal injections of drugs, while effective, is invasive and associated with side effects such as retinal detachment and endophthalmitis. In this work, we have formulated a model compound, rapamycin (RAP), in nanoparticle-based eye drops and evaluated the delivery of RAP to the posterior eye tissues in a healthy rabbit. We have also studied the formulation in experimental autoimmune uveitis (EAU) mouse model with retinal inflammation. Aqueous RAP eye drops were prepared using N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (Molecular Envelope Technology - MET) containing 0.23 ± 0.001% w/v RAP with viscosity, osmolarity, and pH within the ocular comfort range, and the formulation (MET-RAP) was stable in terms of drug content at both refrigeration and room temperature for one month. The MET-RAP eye drops delivered RAP to the choroid-retina with a Cmax of 145 ± 49 ng/g (tmax = 1 hour). The topical application of the MET-RAP eye drops to the EAU mouse model resulted in significant disease suppression compared to controls, with activity similar to dexamethasone eye drops. The MET-RAP eye drops also resulted in a reduction of RORγt and an increase in both Foxp3 expression and IL-10 secretion, indicating a mechanism involving the inhibition of Th17 cells and the up-regulation of T-reg cells. The MET-RAP formulation delivers RAP to the posterior eye segments, and the formulation is active in EAU.
Type: | Article |
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Title: | The Topical Ocular Delivery of Rapamycin to Posterior Eye Tissues and the Suppression of Retinal Inflammatory Disease |
Location: | Netherlands |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.ijpharm.2022.121755 |
Publisher version: | https://doi.org/10.1016/j.ijpharm.2022.121755 |
Language: | English |
Additional information: | © 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Chitosan, Experimental autoimmune uveitis, MET, RAP, Retina |
UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
URI: | https://discovery.ucl.ac.uk/id/eprint/10147975 |
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