Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies
Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded po...
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MDPI AG
2021-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/2/228 |
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| author | Deyanira Barbosa-Alfaro Vanessa Andrés-Guerrero Ivan Fernandez-Bueno María Teresa García-Gutiérrez Esther Gil-Alegre Irene Teresa Molina-Martínez José Carlos Pastor-Jimeno Rocío Herrero-Vanrell Irene Bravo-Osuna |
| author_facet | Deyanira Barbosa-Alfaro Vanessa Andrés-Guerrero Ivan Fernandez-Bueno María Teresa García-Gutiérrez Esther Gil-Alegre Irene Teresa Molina-Martínez José Carlos Pastor-Jimeno Rocío Herrero-Vanrell Irene Bravo-Osuna |
| author_sort | Deyanira Barbosa-Alfaro |
| collection | DOAJ |
| description | Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic-<i>co</i>-glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O/W) emulsion solvent evaporation technique. MS were characterized in terms of mean particle size and particle size distribution, external morphology, polymer integrity, drug content, and in vitro release profiles. MS were sterilized by gamma irradiation (25 kGy), and dexamethasone release profiles from sterilized and non-sterilized microspheres were compared by means of the similarity factor (f<sub>2</sub>). The mechanism of drug release before and after irradiation exposure of Dx-MS was identified using appropriate mathematical models. Dexamethasone release was sustained in vitro for 9 weeks. The evaluation of the in vivo tolerance was carried out in rabbit eyes, which received a sub-Tenon injection of 5 mg of sterilized Dx-MS (20–53 µm size containing 165.6 ± 3.6 µg Dx/mg MS) equivalent to 828 µg of Dx. No detectable increase in intraocular pressure was reported, and clinical and histological analysis of the ocular tissues showed no adverse events up to 6 weeks after the administration. According to the data presented in this work, the sub-Tenon administration of Dx-MS could be a promising alternative to successive intravitreal injections for the treatment of chronic diseases of the back of the eye. |
| first_indexed | 2024-03-09T05:18:16Z |
| format | Article |
| id | doaj.art-906b1e825b40427c82734034b9018514 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T05:18:16Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-906b1e825b40427c82734034b90185142023-12-03T12:43:07ZengMDPI AGPharmaceutics1999-49232021-02-0113222810.3390/pharmaceutics13020228Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance StudiesDeyanira Barbosa-Alfaro0Vanessa Andrés-Guerrero1Ivan Fernandez-Bueno2María Teresa García-Gutiérrez3Esther Gil-Alegre4Irene Teresa Molina-Martínez5José Carlos Pastor-Jimeno6Rocío Herrero-Vanrell7Irene Bravo-Osuna8Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, SpainInnovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, SpainThematic Research Network in Ophthalmology (Oftared) Carlos III National Institute of Health, 28040 Madrid, SpainInstituto Universitario de Oftalmobiología Aplicada (IOBA), Universidad de Valladolid, 47011 Valladolid, SpainInnovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, SpainInnovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, SpainThematic Research Network in Ophthalmology (Oftared) Carlos III National Institute of Health, 28040 Madrid, SpainInnovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, SpainInnovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, SpainMany diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic-<i>co</i>-glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O/W) emulsion solvent evaporation technique. MS were characterized in terms of mean particle size and particle size distribution, external morphology, polymer integrity, drug content, and in vitro release profiles. MS were sterilized by gamma irradiation (25 kGy), and dexamethasone release profiles from sterilized and non-sterilized microspheres were compared by means of the similarity factor (f<sub>2</sub>). The mechanism of drug release before and after irradiation exposure of Dx-MS was identified using appropriate mathematical models. Dexamethasone release was sustained in vitro for 9 weeks. The evaluation of the in vivo tolerance was carried out in rabbit eyes, which received a sub-Tenon injection of 5 mg of sterilized Dx-MS (20–53 µm size containing 165.6 ± 3.6 µg Dx/mg MS) equivalent to 828 µg of Dx. No detectable increase in intraocular pressure was reported, and clinical and histological analysis of the ocular tissues showed no adverse events up to 6 weeks after the administration. According to the data presented in this work, the sub-Tenon administration of Dx-MS could be a promising alternative to successive intravitreal injections for the treatment of chronic diseases of the back of the eye.https://www.mdpi.com/1999-4923/13/2/228dexamethasonepoly(lactic-<i>co</i>-glycolic) acidophthalmologymicrospheresperiocular administrationgamma sterilization |
| spellingShingle | Deyanira Barbosa-Alfaro Vanessa Andrés-Guerrero Ivan Fernandez-Bueno María Teresa García-Gutiérrez Esther Gil-Alegre Irene Teresa Molina-Martínez José Carlos Pastor-Jimeno Rocío Herrero-Vanrell Irene Bravo-Osuna Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies Pharmaceutics dexamethasone poly(lactic-<i>co</i>-glycolic) acid ophthalmology microspheres periocular administration gamma sterilization |
| title | Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies |
| title_full | Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies |
| title_fullStr | Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies |
| title_full_unstemmed | Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies |
| title_short | Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies |
| title_sort | dexamethasone plga microspheres for sub tenon administration influence of sterilization and tolerance studies |
| topic | dexamethasone poly(lactic-<i>co</i>-glycolic) acid ophthalmology microspheres periocular administration gamma sterilization |
| url | https://www.mdpi.com/1999-4923/13/2/228 |
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