Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment
Frequent topical administration of hypotensive eye drops in glaucoma patients may lead to the development of dry eye disease (DED) symptoms, because of tear film destabilization and the adverse effects associated with antiglaucoma formulations. To address all this, in the current study preservative-...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/129111 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/129111 |
| Access Level: | acceso abierto |
| Palabra clave: | 615.4 Latanoprost Hyaluronic acid Liposomes Glaucoma Dry eye disease Ocular drug delivery Ex vivo In vivo Farmacia Oftalmología 3209.08 Preparación de Medicamentos 3209.01 Análisis de Medicamentos 3209.02 Composición de Medicamentos |
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Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatmentMarco BrugneraVicario De La Torre, MartaGonzález-Cela Casamayor, Miriam AnaFelipe M. González-FernándezIlaria FerraboschiAndrés Guerrero, VanesaSara NicoliCristina SissaSilvia PescinaHerrero Vanrell, María Del RocíoBravo Osuna, Irene615.4LatanoprostHyaluronic acidLiposomesGlaucomaDry eye diseaseOcular drug deliveryEx vivoIn vivoFarmaciaOftalmología3209.08 Preparación de Medicamentos3209.01 Análisis de Medicamentos3209.02 Composición de MedicamentosFrequent topical administration of hypotensive eye drops in glaucoma patients may lead to the development of dry eye disease (DED) symptoms, because of tear film destabilization and the adverse effects associated with antiglaucoma formulations. To address all this, in the current study preservative-free latanoprost-loaded (0.005 % w/v) synthetic phosphatidylcholine (1,2-dioleoyl-sn-glycero-3-phosphocholine 0.75 % w/v, 1,2-dimyristoylsn-glycero-3-phosphocholine 0.25 % w/v) liposomes dispersed in the mucoadhesive polymer hyaluronic acid (0.2 % w/v), containing the osmoprotective ingredients betaine (0.40 % w/v) and leucine (0.90 % w/v) (LAT-HALIP), have been prepared and further characterised. Permeation and retention evaluations on a validated ex vivo porcine eye model revealed that the active metabolite latanoprost acid was quantified only starting from LATHA-LIP once passing conjunctiva, sclera and choroid compared to the marketed latanoprost (0.005 % w/v) benchmark (MF). The liposomal formulation outperformed MF when applied to the corneal tissue. Additionally, distribution and interactions within corneal and scleral tissues were investigated by means of two-photon microscopy with liposomal formulations containing coumarin-6. Furthermore, acute and chronic tolerance studies on rabbits revealed no signs of discomfort or ocular damage. Schirmer’s test, tear osmolarity, tear breakup time (TBUT) and fluorescence staining evaluated through the Oxford grading scale, were assessed as DED diagnostic parameters over a 25-day monitoring period; LAT-HA-LIP consistently maintained levels comparable to physiological solution (0.9 % w/v NaCl) used as control, with a slight increase of TBUT values from day 15 (6.00 ± 0.63 s for control, 7.00 ± 0.78 s for LAT-HA-LIP at day 15, p = 0.0066). A daily topical application of LAT-HALIP for 15 consecutive days, effectively lowered IOP in a sustained way (2.51–3.88 mmHg mean IOP reduction over the 5–15-day period). These results highlight the clinical relevance of the proposed technological platform, able to provide IOP reduction during the simulated long-term administration and simultaneous ocular surface protection with potential for the treatment of glaucoma.ElsevierUniversidad Complutense de Madrid20252025-01-2520252025-01-25journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/129111reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1291112026-06-02T12:44:21Z |
| dc.title.none.fl_str_mv |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment |
| title |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment |
| spellingShingle |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment Marco Brugnera 615.4 Latanoprost Hyaluronic acid Liposomes Glaucoma Dry eye disease Ocular drug delivery Ex vivo In vivo Farmacia Oftalmología 3209.08 Preparación de Medicamentos 3209.01 Análisis de Medicamentos 3209.02 Composición de Medicamentos |
| title_short |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment |
| title_full |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment |
| title_fullStr |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment |
| title_full_unstemmed |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment |
| title_sort |
Disclosing lng-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma treatment |
| dc.creator.none.fl_str_mv |
Marco Brugnera Vicario De La Torre, Marta González-Cela Casamayor, Miriam Ana Felipe M. González-Fernández Ilaria Ferraboschi Andrés Guerrero, Vanesa Sara Nicoli Cristina Sissa Silvia Pescina Herrero Vanrell, María Del Rocío Bravo Osuna, Irene |
| author |
Marco Brugnera |
| author_facet |
Marco Brugnera Vicario De La Torre, Marta González-Cela Casamayor, Miriam Ana Felipe M. González-Fernández Ilaria Ferraboschi Andrés Guerrero, Vanesa Sara Nicoli Cristina Sissa Silvia Pescina Herrero Vanrell, María Del Rocío Bravo Osuna, Irene |
| author_role |
author |
| author2 |
Vicario De La Torre, Marta González-Cela Casamayor, Miriam Ana Felipe M. González-Fernández Ilaria Ferraboschi Andrés Guerrero, Vanesa Sara Nicoli Cristina Sissa Silvia Pescina Herrero Vanrell, María Del Rocío Bravo Osuna, Irene |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad Complutense de Madrid |
| dc.subject.none.fl_str_mv |
615.4 Latanoprost Hyaluronic acid Liposomes Glaucoma Dry eye disease Ocular drug delivery Ex vivo In vivo Farmacia Oftalmología 3209.08 Preparación de Medicamentos 3209.01 Análisis de Medicamentos 3209.02 Composición de Medicamentos |
| topic |
615.4 Latanoprost Hyaluronic acid Liposomes Glaucoma Dry eye disease Ocular drug delivery Ex vivo In vivo Farmacia Oftalmología 3209.08 Preparación de Medicamentos 3209.01 Análisis de Medicamentos 3209.02 Composición de Medicamentos |
| description |
Frequent topical administration of hypotensive eye drops in glaucoma patients may lead to the development of dry eye disease (DED) symptoms, because of tear film destabilization and the adverse effects associated with antiglaucoma formulations. To address all this, in the current study preservative-free latanoprost-loaded (0.005 % w/v) synthetic phosphatidylcholine (1,2-dioleoyl-sn-glycero-3-phosphocholine 0.75 % w/v, 1,2-dimyristoylsn-glycero-3-phosphocholine 0.25 % w/v) liposomes dispersed in the mucoadhesive polymer hyaluronic acid (0.2 % w/v), containing the osmoprotective ingredients betaine (0.40 % w/v) and leucine (0.90 % w/v) (LAT-HALIP), have been prepared and further characterised. Permeation and retention evaluations on a validated ex vivo porcine eye model revealed that the active metabolite latanoprost acid was quantified only starting from LATHA-LIP once passing conjunctiva, sclera and choroid compared to the marketed latanoprost (0.005 % w/v) benchmark (MF). The liposomal formulation outperformed MF when applied to the corneal tissue. Additionally, distribution and interactions within corneal and scleral tissues were investigated by means of two-photon microscopy with liposomal formulations containing coumarin-6. Furthermore, acute and chronic tolerance studies on rabbits revealed no signs of discomfort or ocular damage. Schirmer’s test, tear osmolarity, tear breakup time (TBUT) and fluorescence staining evaluated through the Oxford grading scale, were assessed as DED diagnostic parameters over a 25-day monitoring period; LAT-HA-LIP consistently maintained levels comparable to physiological solution (0.9 % w/v NaCl) used as control, with a slight increase of TBUT values from day 15 (6.00 ± 0.63 s for control, 7.00 ± 0.78 s for LAT-HA-LIP at day 15, p = 0.0066). A daily topical application of LAT-HALIP for 15 consecutive days, effectively lowered IOP in a sustained way (2.51–3.88 mmHg mean IOP reduction over the 5–15-day period). These results highlight the clinical relevance of the proposed technological platform, able to provide IOP reduction during the simulated long-term administration and simultaneous ocular surface protection with potential for the treatment of glaucoma. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025-01-25 2025 2025-01-25 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.14352/129111 |
| url |
https://hdl.handle.net/20.500.14352/129111 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM) |
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Universidad Complutense de Madrid (UCM) |
| reponame_str |
Docta Complutense |
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Docta Complutense |
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