Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease
Alfredo Salcedo-Ledesma,1,2 Andrea Córdoba,1 Naomi C Zatarain-Barrón,1 Enrique O Graue-Hernández,1 Yonathan Garfias,3,4 Norma Morales Flores,1 Gustavo A García-Sánchez,5 Diego García-Santisteban,5 Mónica A Linares-Alba,5 Rodrigo García-Santisteban,6 Alejandro Navas1 1Department of Cornea and Refract...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-05-01
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| Series: | Clinical Ophthalmology |
| Subjects: | |
| Online Access: | https://www.dovepress.com/subconjunctival-sirolimus-loaded-liposomes-for-the-treatment-of-modera-peer-reviewed-fulltext-article-OPTH |
| _version_ | 1827952476715745280 |
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| author | Salcedo-Ledesma A Córdoba A Zatarain-Barrón NC Graue-Hernández EO Garfias Y Morales Flores N García-Sánchez GA García-Santisteban D Linares-Alba MA García-Santisteban R Navas A |
| author_facet | Salcedo-Ledesma A Córdoba A Zatarain-Barrón NC Graue-Hernández EO Garfias Y Morales Flores N García-Sánchez GA García-Santisteban D Linares-Alba MA García-Santisteban R Navas A |
| author_sort | Salcedo-Ledesma A |
| collection | DOAJ |
| description | Alfredo Salcedo-Ledesma,1,2 Andrea Córdoba,1 Naomi C Zatarain-Barrón,1 Enrique O Graue-Hernández,1 Yonathan Garfias,3,4 Norma Morales Flores,1 Gustavo A García-Sánchez,5 Diego García-Santisteban,5 Mónica A Linares-Alba,5 Rodrigo García-Santisteban,6 Alejandro Navas1 1Department of Cornea and Refractive Surgery, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico; 2PECEM MD/PhD Program, Faculty of Medicine, UNAM, Mexico City, Mexico; 3Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, Mexico; 4Research Unit, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico; 5Research and Development, Santgar Laboratories, Mexico City, Mexico; 6Faculty of Medicine, Panamerican University, Mexico City, MexicoCorrespondence: Alejandro Navas, Department of Cornea and Refractive Surgery, Institute of Ophthalmology “Conde de Valenciana”, Chimalpopoca 14, Mexico City, 06800, Mexico, Tel +5255 54421700, Fax +5255 55789748, Email alejandro.navas@institutodeoftalmologia.orgPurpose: To determine the effectiveness of subconjunctival application of a novel sirolimus liposomal formulation for the treatment of dry eye.Methods: A randomized, triple-blind, Phase II clinical trial. Thirty-eight eyes of 19 patients were included. Nine patients (18 eyes) assigned to the sham group (Sham) and 10 patients (20 eyes) to sirolimus-loaded liposomes group (Sirolimus). The treatment group received three doses of subconjunctival liposome-encapsulated sirolimus and the sham group received three doses of liposomal suspension without sirolimus. Subjective (Ocular Surface Disease Index, OSDI) and measured (corrected distance visual acuity, conjunctival hyperemia, tear osmolarity, Schirmer’s test, corneal/conjunctival staining and matrix metalloproteinase-9) variables were measured.Results: Sirolimus-entrapped liposomes-treated group OSDI scores changed from 62.19 (± 6.07) to 37.8 (± 17.81) (p=0.0024), and conjunctival hyperemia from 2.0 (± 0.68) to 0.83 (± 0.61) (p< 0.0001); Sham group with OSDI scores from 60.02 (± 14.2) to 36.02 (± 20.70) (p=0.01), and conjunctival hyperemia from 1.33 (± 0.68) to 0.94 (± 0.87) (p=0.048). All the other evaluated outcomes only showed significant differences in the sirolimus group: corneal/conjunctival staining score (p=0.0015), lipid layer interferometry (p=0.006), and inferior meibomian gland dropout (p=0.038). No local or systemic adverse effects regarding the medication itself were reported, and the administration route was well accepted.Conclusion: Our findings suggest that sub-conjunctival sirolimus-loaded liposomes are effective in reducing both signs and symptoms of dry eye in patients with poorly controlled moderate-to-severe DED, while avoiding other topical administration adverse effects. Further investigation with a larger sample size is required to determine long-term effects.Keywords: sirolimus, rapamycin, liposomes, sirolimus liposomal formulation, dry eye disease |
| first_indexed | 2024-04-09T13:58:25Z |
| format | Article |
| id | doaj.art-f7c9f9d561694f049a15df17b143f7f8 |
| institution | Directory Open Access Journal |
| issn | 1177-5483 |
| language | English |
| last_indexed | 2024-04-09T13:58:25Z |
| publishDate | 2023-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Ophthalmology |
| spelling | doaj.art-f7c9f9d561694f049a15df17b143f7f82023-05-07T16:04:05ZengDove Medical PressClinical Ophthalmology1177-54832023-05-01Volume 171295130583529Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye DiseaseSalcedo-Ledesma ACórdoba AZatarain-Barrón NCGraue-Hernández EOGarfias YMorales Flores NGarcía-Sánchez GAGarcía-Santisteban DLinares-Alba MAGarcía-Santisteban RNavas AAlfredo Salcedo-Ledesma,1,2 Andrea Córdoba,1 Naomi C Zatarain-Barrón,1 Enrique O Graue-Hernández,1 Yonathan Garfias,3,4 Norma Morales Flores,1 Gustavo A García-Sánchez,5 Diego García-Santisteban,5 Mónica A Linares-Alba,5 Rodrigo García-Santisteban,6 Alejandro Navas1 1Department of Cornea and Refractive Surgery, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico; 2PECEM MD/PhD Program, Faculty of Medicine, UNAM, Mexico City, Mexico; 3Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, Mexico; 4Research Unit, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico; 5Research and Development, Santgar Laboratories, Mexico City, Mexico; 6Faculty of Medicine, Panamerican University, Mexico City, MexicoCorrespondence: Alejandro Navas, Department of Cornea and Refractive Surgery, Institute of Ophthalmology “Conde de Valenciana”, Chimalpopoca 14, Mexico City, 06800, Mexico, Tel +5255 54421700, Fax +5255 55789748, Email alejandro.navas@institutodeoftalmologia.orgPurpose: To determine the effectiveness of subconjunctival application of a novel sirolimus liposomal formulation for the treatment of dry eye.Methods: A randomized, triple-blind, Phase II clinical trial. Thirty-eight eyes of 19 patients were included. Nine patients (18 eyes) assigned to the sham group (Sham) and 10 patients (20 eyes) to sirolimus-loaded liposomes group (Sirolimus). The treatment group received three doses of subconjunctival liposome-encapsulated sirolimus and the sham group received three doses of liposomal suspension without sirolimus. Subjective (Ocular Surface Disease Index, OSDI) and measured (corrected distance visual acuity, conjunctival hyperemia, tear osmolarity, Schirmer’s test, corneal/conjunctival staining and matrix metalloproteinase-9) variables were measured.Results: Sirolimus-entrapped liposomes-treated group OSDI scores changed from 62.19 (± 6.07) to 37.8 (± 17.81) (p=0.0024), and conjunctival hyperemia from 2.0 (± 0.68) to 0.83 (± 0.61) (p< 0.0001); Sham group with OSDI scores from 60.02 (± 14.2) to 36.02 (± 20.70) (p=0.01), and conjunctival hyperemia from 1.33 (± 0.68) to 0.94 (± 0.87) (p=0.048). All the other evaluated outcomes only showed significant differences in the sirolimus group: corneal/conjunctival staining score (p=0.0015), lipid layer interferometry (p=0.006), and inferior meibomian gland dropout (p=0.038). No local or systemic adverse effects regarding the medication itself were reported, and the administration route was well accepted.Conclusion: Our findings suggest that sub-conjunctival sirolimus-loaded liposomes are effective in reducing both signs and symptoms of dry eye in patients with poorly controlled moderate-to-severe DED, while avoiding other topical administration adverse effects. Further investigation with a larger sample size is required to determine long-term effects.Keywords: sirolimus, rapamycin, liposomes, sirolimus liposomal formulation, dry eye diseasehttps://www.dovepress.com/subconjunctival-sirolimus-loaded-liposomes-for-the-treatment-of-modera-peer-reviewed-fulltext-article-OPTHsirolimusrapamycinliposomessirolimus liposomal formulationdry eye disease. |
| spellingShingle | Salcedo-Ledesma A Córdoba A Zatarain-Barrón NC Graue-Hernández EO Garfias Y Morales Flores N García-Sánchez GA García-Santisteban D Linares-Alba MA García-Santisteban R Navas A Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease Clinical Ophthalmology sirolimus rapamycin liposomes sirolimus liposomal formulation dry eye disease. |
| title | Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease |
| title_full | Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease |
| title_fullStr | Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease |
| title_full_unstemmed | Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease |
| title_short | Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease |
| title_sort | subconjunctival sirolimus loaded liposomes for the treatment of moderate to severe dry eye disease |
| topic | sirolimus rapamycin liposomes sirolimus liposomal formulation dry eye disease. |
| url | https://www.dovepress.com/subconjunctival-sirolimus-loaded-liposomes-for-the-treatment-of-modera-peer-reviewed-fulltext-article-OPTH |
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