Micelles of progesterone for topical eye administration: interspecies and intertissues differences in Ex vivo ocular permeability
Open accessAbstract
Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of efficient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability; and (ii) to compare drug diffusion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies differences. Micelles of Pluronic F68 (3-4 nm) and Soluplus (52-59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation efficiency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen's egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the differences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.
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Pluronic micelles increased PG solubility by an order of magnitude in a buffered medium at pH 7.4, whereas Soluplus formulations enhanced apparent solubility by two orders of magnitude.
“The results indicated that Pluronic micelles increased PG solubility by an order of magnitude in a buffered medium at pH 7.4, whereas Soluplus formulations enhanced apparent solubility by two orders of magnitude.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [200]
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Kahraman, E., Durgun, M. E., Güngör, S., & Özsoy, Y. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-89868-3.00011-2
Hamedani, Y. P., Hurst, J., Ritter, M. U., Weingarten, P., Skokowa, J., Schnichels, S., & Adams, F. (2025) · Macromolecular Rapid Communications · doi:10.1002/marc.202500788
- Authors
- Alambiaga-Caravaca, A. M., Calatayud-Pascual, M. A., Rodilla, V., Concheiro, A., López-Castellano, A., & Alvarez-Lorenzo, C.
- Affiliations
- Departamento de Farmacia, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Cardenal Herrera-CEU, CEU Universities, C/Santiago Ramón y Cajal, s/n., Alfara del Patriarca, 46115 Valencia, Spain
- Universidad Cardenal Herrera CEU (ES)
- Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma Group, Facultad de Farmacia, and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- ORCID
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2020-07-26
- Volume
- 12
- Issue
- 8
- Pages
- 702
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC7464168
- OpenAlex
- W3045410463
- Cited by
- 38
- References
- 57
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 3
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (acceptedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Hispana (submittedVersion, cc-by)
- Repositorio institucional da Universidade de Santiago de Compostela (University of Santiago de Compostela) (submittedVersion, cc-by)
- CEU Repositorio Institucional (Fundación Universitaria San Pablo CEU) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministerio de Economía, Industria y Competitividad, Gobierno de España (SAF2017-83118-R)
- Xunta de Galicia (AEMAT ED431E 2018/08)
- CEU-Cardenal Herrera University (INDI 19/28)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- progesterone, ocular permeability, poloxamer 188, Soluplus, cornea, sclera, species differences, retinitis pigmentosa, drug solubility enhancement, in situ gelling, HET-CAM test, ocular bioavailability
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