2026-06-25T20:02:18Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1180242025-02-13T01:09:59Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Arranz Romera, Alicia author Esteban-Pérez, Sergio author Molina Martínez, Irene Teresa author Bravo Osuna, Irene author Herrero Vanrell, María Del Rocío 2025-02-12T15:46:45Z 2025-02-12T15:46:45Z 2021-01-26 Arranz-Romera A, Esteban-Pérez S, Molina-Martínez IT, Bravo-Osuna I, Herrero-Vanrell R. Co-delivery of glial cell–derived neurotrophic factor (Gdnf) and tauroursodeoxycholic acid (Tudca) from PLGA microspheres: potential combination therapy for retinal diseases. Drug Deliv and Transl Res [Internet]. abril de 2021 [citado 12 de febrero de 2025];11(2):566-80. Disponible en: https://link.springer.com/10.1007/s13346-021-00930-9 10.1007/s13346-021-00930-9 https://hdl.handle.net/20.500.14352/118024 https://dx.doi.org/10.1007/s13346-021-00930-9 Retinitis pigmentosa (RP) is a group of genetically diverse inherited disorders characterised by the progressive photoreceptors and pigment epithelial cell dysfunction leading to central vision impairment. Although important advances in the understanding of the pathophysiologic pathways involved in RP have been made, drug delivery for the treatment of ocular disorders afecting the posterior segment of the eye is still an unmet clinical need. In the present study, we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating two neuroprotectants agents (glial cell-line-derived neurotrophic factor—GDNF and Tauroursodeoxycholic acid—TUDCA) as a potential therapeutic tool for the treatment of RP. A solid-in-oil-in-water (S/O/W) emulsion solvent extraction-evaporation technique was employed for MS preparation. A combination of PLGA and vitamin E was used to create the microcarriers. The morphology, particle size, encapsulation efciency and in vitro release profle of the MSs were studied. Encapsulation efciencies of GDNF and TUDCA for the initial multiloaded MSs, prepared with methylene chloride (MC) as organic solvent and polyvinyl alcohol (PVA) solution in the external phase, were 28.53±0.36% and 45.65±8.01% respectively. Diferent technological parameters to optimise the formulation such as the incorporation of a water-soluble co-solvent ethanol (EtOH) in the internal organic phase, as well as NaCl concentration, and viscosity using a viscosizing agent (hydroxypropyl methylcellulose—HPMC) in the external aqueous phase were considered. EtOH incorporation and external phase viscosity of the emulsion were critical attributes for improving drug loading of both compounds. In such a way, when using a methylene chloride/EtOH ratio 75:25 into the inner organic phase and the viscosity agent HPMC (1% w/v) in the external aqueous phase, GDNF and TUDCA payloads resulted 48.86±1.49% and 78.58±10.40% respectively, and a decrease in the initial release of GDNF was observed (22.03±1.41% compared with 40.86±6.66% of the initial multi-loaded formulation). These optimised microparticles exhibited sustained in vitro releases over 91 days. These results suggest that the microencapsulation procedure optimised in this work presents a promising technological strategy for the development of multi-loaded intraocular drug delivery systems (IODDS). eng Attribution-NoDerivatives 4.0 International Co‐delivery of glial cell–derived neurotrophic factor (GDNF) and tauroursodeoxycholic acid (TUDCA) from PLGA microspheres: potential combination therapy for retinal diseases journal article UGFyYSBxdWUgZWwgcmVwb3NpdG9yaW8gaW5zdGl0dWNpb25hbCBkZSBsYSBVbml2ZXJzaWRhZCBkZSBNYWRyaWQgcHVlZGEgYWxtYWNlbmFyIHkgZGlzdHJpYnVpciBlbCBvYmpldG8gZGlnaXRhbCBkZXBvc2l0YWRvLCBlcyBuZWNlc2FyaW8gcXVlIGxhIHBlcnNvbmEgcXVlIGhhZ2EgZWwgZGVww7NzaXRvIGxlYSB5IGFjZXB0ZSBsYXMgY29uZGljaW9uZXMgZXN0YWJsZWNpZGFzIGVuIGVzdGEgbGljZW5jaWE6CuKAoiBBY2VwdGFuZG8gZXN0YSBsaWNlbmNpYSwgdXN0ZWQgY29tbyBhdXRvci9yZXMgeS9vIHByb3BpZXRhcmlvL3MgZGUgbG9zIGRlcmVjaG9zIGRlIHByb3BpZWRhZCBpbnRlbGVjdHVhbCwgbyBsYSBwZXJzb25hIGRlbGVnYWRhIHBhcmEgaGFjZXJsbyAsIG90b3JnYSBhbCByZXBvc2l0b3JpbyBkZSBsYSBVbml2ZXJzaWRhZCBDb21wbHV0ZW5zZSBkZSBNYWRyaWQgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNjacOzbiB5IGRpc3RyaWJ1Y2nDs24gZGUgc3Ugb2JyYSBlbiBjdWFscXVpZXIgZm9ybWF0byB5IG1lZGlvLgrigKIgRWwgZGVwb3NpdGFudGUsIGVuIGNhc28gZGUgdW5hIG9icmEgY29uIG3DoXMgZGUgdW4gYXV0b3IsIGdhcmFudGl6YSBxdWUgbG8gaGFjZSByZXNwb25zYWJsZW1lbnRlIGVuIG5vbWJyZSB5IGNvbiBjb25zZW50aW1pZW50byBkZSBsb3MgZGVtw6FzIGF1dG9yZXMuCuKAoiBBY2VwdGEgcXVlIGVsIHJlcG9zaXRvcmlvIGRlIGxhIFVuaXZlcnNpZGFkIENvbXBsdXRlbnNlIGRlIE1hZHJpZCBwdWVkYSBjb25zZXJ2YXIgbcOhcyBkZSB1bmEgY29waWEgZGUgZXN0ZSBkb2N1bWVudG8geSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXJsbyBhIGN1YWxxdWllciBmb3JtYXRvIGRlIGZpY2hlcm8sIG1lZGlvIG8gc29wb3J0ZSwgcGFyYSBwcm9ww7NzaXRvcyBkZSBzZWd1cmlkYWQgeSBwcmVzZXJ2YWNpw7NuLgrigKIgRGVjbGFyYSBxdWUgZWwgZG9jdW1lbnRvIGVzIHVuIHRyYWJham8gb3JpZ2luYWwgc3V5bywgbyBxdWUgZXMgbGEgcGVyc29uYSBkZWxlZ2FkYSBwYXJhIHJlYWxpemFyIGVsIGRlcMOzc2l0byB5LCBwb3IgdGFudG8sIGN1ZW50YSBjb24gbGEgcG90ZXN0YWQgcGFyYSBvdG9yZ2FyIGxvcyBkZXJlY2hvcyBjb250ZW5pZG9zIGVuIGVzdGEgbGljZW5jaWEuIFRhbWJpw6luIGRlY2xhcmEgcXVlIHN1IGRvY3VtZW50byBubyBpbmZyaW5nZSBsbyBlc3RhYmxlY2lkbyBlbiBsYSB2aWdlbnRlIGxlZ2lzbGFjacOzbiBkZSBwcm9waWVkYWQgaW50ZWxlY3R1YWwuCuKAoiBTaSBlbCBkb2N1bWVudG8gY29udGllbmUgbWF0ZXJpYWxlcyBkZSBsb3MgY3VhbGVzIG5vIHRpZW5lIGxvcyBkZXJlY2hvcyBkZSBhdXRvciwgZGVjbGFyYSBxdWUgaGEgb2J0ZW5pZG8gZWwgcGVybWlzbyBzaW4gcmVzdHJpY2Npw7NuIGRlbCBwcm9waWV0YXJpbyBwYXJhIG90b3JnYXIgYSBsYSBVbml2ZXJzaWRhZCBDb21wbHV0ZW5zZSBkZSBNYWRyaWQgbG9zIGRlcmVjaG9zIHJlcXVlcmlkb3MgcG9yIGVzdGEgbGljZW5jaWEsIHkgcXVlIGVzZSBtYXRlcmlhbCwgY3V5b3MgZGVyZWNob3Mgc29uIGRlIHRlcmNlcm9zLCBlc3TDoSBjbGFyYW1lbnRlIGlkZW50aWZpY2FkbyB5IHJlY29ub2NpZG8gZGVudHJvIGRlbCBjb250ZW5pZG8gZGVsIGRvY3VtZW50by4K4oCiIFNpIGVsIGRvY3VtZW50byBzZSBiYXNhIGVuIHVuYSBvYnJhIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRhIG8gYXBveWFkYSBwb3IgdW5hIGFnZW5jaWEgdSBvcmdhbml6YWNpw7NuIGRpZmVyZW50ZSBkZSBsYSBVbml2ZXJzaWRhZCBDb21wbHV0ZW5zZSBkZSBNYWRyaWQsIHVzdGVkIGRlY2xhcmEgcXVlIGhhIGN1bXBsaWRvIGNvbiBsYXMgb2JsaWdhY2lvbmVzIHJlcXVlcmlkYXMgcG9yIGVzdGUgY29udHJhdG8gbyBhY3VlcmRvLgrigKIgTGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkIGlkZW50aWZpY2Fyw6EgY2xhcmFtZW50ZSBzdS9zIG5vbWJyZS9zIGNvbW8gZWwvbG9zIGF1dG9yL2VzIG8gcHJvcGlldGFyaW8vcyBkZSBsb3MgZGVyZWNob3MgZGVsIGRvY3VtZW50bywgeSBubyBoYXLDoSBuaW5ndW5hIGFsdGVyYWNpw7NuIGRlIHN1IGRvY3VtZW50byBkaWZlcmVudGUgYSBsYXMgcGVybWl0aWRhcyBlbiBlc3RhIGxpY2VuY2lhLgrigKIgVHJhYmFqb3MgZGVwb3NpdGFkb3MgcG9yIHN1IHByb3BpbyBhdXRvcjogYWwgYXV0by1hcmNoaXZhciBlc3RhIGNvbGVjY2nDs24gZGUgZmljaGVyb3MgeSBtZXRhZGF0b3MgYmlibGlvZ3LDoWZpY29zIGFzb2NpYWRvcywgb3RvcmdvIGFsIHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwgZGUgbGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkIGVsIGRlcmVjaG8gcGFyYSBhbG1hY2VuYXJsb3MgeSBkaXN0cmlidWlybG9zLiBEZWNsYXJvIHF1ZSBlc3RlIG1hdGVyaWFsIGVzIGRlIG1pIHByb3BpZWRhZCBpbnRlbGVjdHVhbCB5IHF1ZSBlbCByZXBvc2l0b3JpbyBpbnN0aXR1dGljaW9uYWwgZGUgbGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkLCBubyBhc3VtZSByZXNwb25zYWJpbGlkYWQgYWxndW5hIGVuIGNhc28gZGUgcXVlIHNlIHByb2R1emNhIHVuYSB2aW9sYWNpw7NuIGRlIGRlcmVjaG9zIGRlIHByb3BpZWRhZCBhbCBkaXN0cmlidWlyIGVzdG9zIGZpY2hlcm9zIG8gbWV0YWRhdG9zLgrigKIgVHJhYmFqb3MgZGVwb3NpdGFkb3MgcG9yIG90cm9zIHF1ZSBubyBzZWFuIHN1IGF1dG9yOiBkZWNsYXJvIHF1ZSBsb3MgbWV0YWRhdG9zIGJpYmxpb2dyw6FmaWNvcyBxdWUgZXN0b3kgYXJjaGl2YW5kbyBlbiBlbCByZXBvc2l0b3JpbyBpbnN0aXR1Y2lvbmFsIGRlIGxhIFVuaXZlcnNpZGFkIENvbXBsdXRlbnNlIGRlIE1hZHJpZCwgc29uIGRlIGRvbWluaW8gcMO6YmxpY28uIFNpIG5vIGZ1ZXNlIGVsIGNhc28sIGFjZXB0byBwbGVuYSByZXNwb25zYWJpbGlkYWQgcG9yIGN1YWxxdWllciBpbmZyYWNjacOzbiBkZSBkZXJlY2hvcyBkZSBhdXRvciBxdWUgY29ubGxldmUgbGEgZGlzdHJpYnVjacOzbiBkZSBlc3RvcyBmaWNoZXJvcyBvIG1ldGFkYXRvcy4K4oCiIFBvciB0YW50bywgdG9kb3MgbG9zIG1ldGFkYXRvcyBwdWJsaWNhZG9zIGVuIGVsIHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwgZGUgbGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkLCBlc3TDoW4gZGlzcG9uaWJsZXMgY29uIGxhIGxpY2VuY2lhIENyZWF0aXZlIENvbW1vbnMgQ0MwIDEuMCBVbml2ZXJzYWwgT2ZyZWNpbWllbnRvIGFsIERvbWluaW8gUMO6YmxpY28gKENDMCAxLjApLiBFc3RhIGxpY2VuY2lhIHBlcm1pdGUgY29waWFyLCBtb2RpZmljYXIsIGRpc3RyaWJ1aXIsIHJldXRpbGl6YXIgeSBjb21wYXJ0aXIgcMO6YmxpY2EgeSBsaWJyZW1lbnRlIGxvcyBtZXRhZGF0b3MgKGluY2x1eWVuZG8gc3UgdXNvIGNvbWVyY2lhbCksIHNpbiB0ZW5lciBxdWUgcGVkaXIgcGVybWlzby4gU2kgdGVyY2VyYXMgcGFydGVzIHVzYW4gZXN0b3MgbWV0YWRhdG9zLCBkZWJlbiBoYWNlciB1biByZWNvbm9jaW1pZW50byB5IHVuYSBhdHJpYnVjacOzbiBhIGxhcyBmdWVudGVzIGRlIGxvcyBtaXNtb3MuIExhIHJldXRpbGl6YWNpw7NuIGRlIGVzdG9zIG1ldGFkYXRvcyB0YW1iacOpbiBlcyBsaWJyZSwgdGFsIHkgY29tbyBlc3RhYmxlY2UgbGEgbGljZW5jaWEgZGUgdXNvIENDMC4K URL https://docta.ucm.es/bitstreams/35eda4fd-7dea-4e2e-804d-c0d62987c661/download File MD5 e8b4c9152731416220a7969e346f2a7c 1808509 application/pdf GDNF TUDCA DDTR 2021.pdf