Academic Journal
Organotypic retinal cultures as an ex vivo screening platform for PLGA-based neuroprotective microspheres.
| Τίτλος: | Organotypic retinal cultures as an ex vivo screening platform for PLGA-based neuroprotective microspheres. |
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| Συγγραφείς: | García-Caballero C; Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Universidad Complutense de Madrid (UCM), Madrid, Spain., Morilla-Lomeña C; Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Universidad Complutense de Madrid (UCM), Madrid, Spain; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Universidad complutense de Madrid (UCM), IdISSC, Madrid, Spain; University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain., Vicario-de-la-Torre M; Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Universidad Complutense de Madrid (UCM), Madrid, Spain; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Universidad complutense de Madrid (UCM), IdISSC, Madrid, Spain; University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain., Andrés-Guerrero V; Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Universidad Complutense de Madrid (UCM), Madrid, Spain; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Universidad complutense de Madrid (UCM), IdISSC, Madrid, Spain; University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain., Ueffing M; Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany., Herrero-Vanrell R; Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Universidad Complutense de Madrid (UCM), Madrid, Spain; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Universidad complutense de Madrid (UCM), IdISSC, Madrid, Spain; University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain., Arango-Gonzalez B; Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany. Electronic address: blanca.arango-gonzalez@klinikum.uni-tuebingen.de., Bravo-Osuna I; Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Universidad Complutense de Madrid (UCM), Madrid, Spain; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Universidad complutense de Madrid (UCM), IdISSC, Madrid, Spain; University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain. Electronic address: ibravo@ucm.es. |
| Πηγή: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2026 Aug 01; Vol. 223, pp. 107555. Date of Electronic Publication: 2026 May 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science B.V Country of Publication: Netherlands NLM ID: 9317982 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0720 (Electronic) Linking ISSN: 09280987 NLM ISO Abbreviation: Eur J Pharm Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Science B.V Original Publication: Amsterdam ; New York : Elsevier, c1993- |
| Ιατρικοί όροι (MeSH): | Glial Cell Line-Derived Neurotrophic Factor*/administration & dosage , Glial Cell Line-Derived Neurotrophic Factor*/chemistry , Retina*/drug effects , Lactic Acid*/chemistry , Lactic Acid*/administration & dosage , Neuroprotective Agents*/administration & dosage , Neuroprotective Agents*/chemistry , Polyglycolic Acid*/chemistry , Polyglycolic Acid*/administration & dosage , alpha-Tocopherol*/administration & dosage , alpha-Tocopherol*/chemistry , Microspheres*, Animals ; Polylactic Acid-Polyglycolic Acid Copolymer ; Rats ; Organ Culture Techniques ; Animals, Newborn ; Rats, Sprague-Dawley ; Drug Delivery Systems |
| Περίληψη: | In this study, the suitability of organotypic cultures of neonatal rat retina as a controlled ex vivo platform for the evaluation of intraocular microparticulate drug delivery systems is assessed, while also exploring their ability to identify formulation-dependent differences. Poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with glial cell line-derived neurotrophic factor (GDNF) and/or α-tocopherol acetate (VitE) were evaluated in short-term (7 days) and long-term (20 days) retinal explant cultures. Retinas from wild-type rats were explanted at postnatal day 9 or 10 and cultured with GDNF/VitE-loaded microspheres with different VitE content (PLGA-E20-GDNF and PLGA-E40-GDNF), VitE-loaded microspheres (PLGA-E20 and PLGA-E40), blank microspheres (PLGA), or left untreated. After exposures, retinal sections were analyzed by immunohistochemistry and TUNEL assay. In short-term cultures, both GDNF/VitE-loaded formulations significantly reduced photoreceptor cell death, whereas in long-term cultures a significant reduction of TUNEL-positive cells was only observed for the PLGA-E40-GDNF formulation. The formulation containing higher VitE content showed a greater neuroprotective effect despite lower GDNF loading, suggesting a possible contribution of VitE to the overall effect. No signs of cytotoxicity or structural damage were observed. The concordance between the present ex vivo findings and previously reported in vivo data in terms of neuroprotective efficacy and biocompatibility supports the use of organotypic retinal cultures as an intermediate ex vivo model to evaluate ocular drug delivery systems. (Copyright © 2026. Published by Elsevier B.V.) |
| Competing Interests: | Declaration of competing interest The authors declare no conflicts of interest. |
| Contributed Indexing: | Keywords: Biocompatibility; Ex vivo screening platform; Intraocular drug delivery systems; Neuroprotection; PLGA microspheres; Retinal organotypic cultures |
| Substance Nomenclature: | 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) 0 (Glial Cell Line-Derived Neurotrophic Factor) 33X04XA5AT (Lactic Acid) 0 (Neuroprotective Agents) 26009-03-0 (Polyglycolic Acid) H4N855PNZ1 (alpha-Tocopherol) |
| Entry Date(s): | Date Created: 20260516 Date Completed: 20260613 Latest Revision: 20260614 |
| Update Code: | 20260615 |
| DOI: | 10.1016/j.ejps.2026.107555 |
| PMID: | 42142812 |
| Βάση Δεδομένων: | MEDLINE |
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