pharmaceutics Article Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-β- Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model Xurxo García-Otero 1,2,† , Cristina Mondelo-García 3,4,† , Francisco González 5,6,† , Roman Perez-Fernandez 7 , Leandro Avila 7 , Jose Ramón Antúnez-López 8 , Miguel González-Barcia 3,4 , Alfredo Adan 9 , Pablo Aguiar 2 , Francisco J. Otero-Espinar 1,10, * , Maria A. Bermúdez 7, * and Anxo Fernández-Ferreiro 3,4, *   Citation: García-Otero, X.; Mondelo-García, C.; González, F.; Perez-Fernandez, R.; Avila, L.; Antúnez-López, J.R.; González-Barcia, M.; Adan, A.; Aguiar, P.; Otero-Espinar, F.J.; et al. Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-β- Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model. Pharmaceutics 2021, 13, 1737. https://doi.org/10.3390/ pharmaceutics13101737 Academic Editor: Marzia Cirri Received: 1 September 2021 Accepted: 14 October 2021 Published: 19 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Pharmacology, Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15705 Santiago de Compostela, Spain; xurxo.garcia@rai.usc.es 2 Molecular Imaging Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; pablo.aguiar.fernandez@sergas.es 3 Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain; cristina.mondelo.garcia@sergas.es (C.M.-G.); miguel.gonzalez.barcia@sergas.es (M.G.-B.) 4 Clinical Pharmacology Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain 5 Surgery Department–CIMUS, University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Spain; francisco.gonzalez@usc.es 6 Ophthalmology Service, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15782 Santiago de Compostela, Spain 7 Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Santiago de Compostela, Spain; roman.perez.fernandez@usc.es (R.P.-F.); leandro.avila@usc.es (L.A.) 8 Pathological Anatomy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain; jose.ramon.antunez.lopez@sergas.es 9 Department of Ophthalmology, Hospital Clinic of Barcelona, 08036 Barcelona, Spain; amadan@clinic.cat 10 Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain * Correspondence: francisco.otero@usc.es (F.J.O.-E.); maria.alvarez.bermudez@udc.es (M.A.B.); anxordes@gmail.com (A.F.-F.) † The authors contributed equally to this work. Abstract: Background: Uveitis is an infrequent disease which constitutes a major cause of ocular morbidity. Correct management is essential, being corticosteroids its cornerstone. In case of con- traindication to corticosteroids or treatment failure, the use of topical tacrolimus (TAC) could be an alternative which has already demonstrated safety and effectiveness in other ocular pathologies. However, TAC eye drops are not marketed, thus their elaboration must be carried out in Hospital Pharmacy Departments (HPDs). Methods: 32 Sprague-Dawley rats were divided into 4 groups of 8 rats each: (a) untreated healthy rats (Healthy); (b) untreated Endotoxin-Induced Uveitis model-rats (EIU); (c) EIU-rats treated with standard treatment of dexamethasone ophthalmic drops (DXM) and (d) EIU-rats treated with TAC-hydroxypropyl-β-cyclodextrin eye drops previously developed by our group (TAC-HPβCD). The mRNA expression levels of IL-6, IL-8, MIP-1α and TNF-α, quantita- tive analysis of leucocytes in aqueous humor and histological evaluation were performed. Results: TAC-HPβCD eye drops demonstrated to reduce ocular inflammation, expression of IL-6, TNF-α, MIP-1α and leukocyte infiltration in aqueous humor. Conclusions: TAC-HPβCD eye drops showed beneficial effect in EIU model in rats, positioning as an alternative for uveitis treatment in case of corticosteroids resistance or intolerance. Keywords: endotoxin-induced uveitis; tacrolimus; eye drops; hydroxypropyl-β-cyclodextrin; inter- leukins; immunosuppressants Pharmaceutics 2021, 13, 1737. https://doi.org/10.3390/pharmaceutics13101737 https://www.mdpi.com/journal/pharmaceutics