Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy
Open accessAbstract
Polymeric micelles of single and mixed poloxamines (Tetronic) were evaluated regarding their ability to host the antiglaucoma agent ethoxzolamide (ETOX) for topical ocular application. Three highly hydrophilic varieties of poloxamine (T908, T1107 and T1307) and a medium hydrophilic variety (T904), possessing a similar number of propylene oxide units but different contents in ethylene oxide, were chosen for the study. The critical micellar concentration and the cloud point of mixed micelles in 0.9 per cent NaCl were slightly greater than the values predicted from the additive rule, suggesting that the co-micellization is hindered. Micellar size ranged between 17 and 120 nm and it was not altered after the loading of ETOX (2.7-11.5 mg drug g(-1) poloxamine). Drug solubilization ability ranked in the order: T904 (50-fold increase in the apparent solubility) > T1107 is approximately equal to T1307 > T908. Mixed micelles showed an intermediate capability to host ETOX but a greater physical stability, maintaining almost 100 per cent drug solubilized after 28 days. Furthermore, the different structural features of poloxamines and their combination in mixed micelles enabled the tuning of drug release profiles, sustaining the release in the 1-5 days range. These findings together with promising hen's egg test-chorioallantoic membrane biocompatibility tests make poloxamine micelles promising nanocarriers for carbonic anhydrase inhibitors in the treatment of glaucoma.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mixed poloxamine PMs (Tetronic) delivering ETOX conserved therapeutically relevant drug dissolution levels over 28 days post-administration.
“These MMs conserved therapeutically relevant drug dissolution levels over 28 days post-administration.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [157]
The Ethoxzolamide solubilization section (p. 7) reports that mixed micelles retained nearly 100% of encapsulated ETOX over 28 days, but this was a storage-stability measurement, not a post-administration result. The paper describes sustained release over 1–5 days (p. 1); it does not establish therapeutically relevant drug levels for 28 days after administration. (LLM, conf=0.90)
Experimental — accuracy not yet measuredCo-micellization of poloxamines upgrades stability of drug-loaded formulations and allows modulation of drug loading and release process.
“The co-micellization of poloxamines upgrades the stability of drug-loaded formulations and allow the modulation of drug loading and release process [157].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [157]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Carbonic anhydrases: novel therapeutic applications for inhibitors and activators
Supuran, C. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2467 · Cited by 3,226 · see citing works
Supuran, C. T., Scozzafava, A., & Casini, A. (2002) · Medicinal Research Reviews · doi:10.1002/med.10025 · Cited by 1,477 · see citing works
Micellization of mixed nonionic surface active agents
Clint, J. H. (1975) · Journal of the Chemical Society Faraday Transactions 1 Physical Chemistry in Condensed Phases · doi:10.1039/f19757101327 · Cited by 1,044 · see citing works
Permeability of cornea, sclera, and conjunctiva: A literature analysis for drug delivery to the eye
Prausnitz, M. R., & Noonan, J. S. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js9802594 · Cited by 630 · see citing works
Supuran, C. T. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.05.009 · Cited by 621 · see citing works
Chiappetta, D. A., & Sosnik, A. (2007) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2007.03.022 · Cited by 570 · see citing works
Self-citationPolymeric nanoparticulate system: A potential approach for ocular drug delivery
Nagarwal, R. C., Kant, S., Singh, P., Maiti, P., & Pandit, J. K. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.12.018 · Cited by 481 · see citing works
wei, Z., Hao, J., Yuan, S., Li, Y., Juan, W., Sha, X., & Fang, X. (2009) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2009.04.030 · Cited by 426 · see citing works
Schroeter, L. C. (1966) · Elsevier eBooks · doi:10.1016/b978-0-08-011432-3.50006-x · Cited by 326 · see citing works
Kabanov, A. V., Batrakova, E. V., & Miller, D. W. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00176-x · Cited by 325 · see citing works
The chick chorioallantoic membrane as a novel in vivo model for the testing of biomaterials
Valdes, T. I., Kreutzer, D. L., & Moussy, F. G. (2002) · Journal of Biomedical Materials Research · doi:10.1002/jbm.10152 · Cited by 192 · see citing works
Chiappetta, D. A., Höcht, C., Taira, C. A., & Sosnik, A. (2009) · Nanomedicine · doi:10.2217/nnm.09.90 · Cited by 174 · see citing works
Self-citationGupta, A. K. (2000) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(00)00508-1 · Cited by 160 · see citing works
Maren, T. H., Jankowska, L., Sanyal, G., et al. (1983) · Experimental Eye Research · doi:10.1016/0014-4835(83)90041-6 · Cited by 158 · see citing works
Self-Associative Behavior and Drug-Solubilizing Ability of Poloxamine (Tetronic) Block Copolymers
González-López, J., Alvarez‐Lorenzo, C., Taboada, P., Sosnik, A., Sández-Macho, I., & Concheiro, Á. (2008) · Langmuir · doi:10.1021/la8016563 · Cited by 142 · see citing works
Self-citationDey, S., Patel, J., Anand, B. S., Jain-Vakkalagadda, B., Kaliki, P., Pal, D., Ganapathy, V., & Mitra, A. K. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-1142 · Cited by 128 · see citing works
Liaw, J., Chang, S.-F., & Hsiao, F.-C. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301485 · Cited by 125 · see citing works
Bioinspired Imprinted PHEMA-Hydrogels for Ocular Delivery of Carbonic Anhydrase Inhibitor Drugs
Ribeiro, A. M., Veiga, F., Santos, D. F. G., Torres-Labandeira, J. J., Concheiro, Á., & Alvarez‐Lorenzo, C. (2011) · Biomacromolecules · doi:10.1021/bm101562v · Cited by 121 · see citing works
Self-citationTetronic micellization, gelation and drug solubilization: Influence of pH and ionic strength
Alvarez‐Lorenzo, C., González-López, J., Fernandez-Tarrio, M., Sández-Macho, I., & Concheiro, Á. (2006) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2006.10.010 · Cited by 113 · see citing works
Self-citationda Silva, R. C., & Loh, W. (1998) · Journal of Colloid and Interface Science · doi:10.1006/jcis.1998.5456 · Cited by 112 · see citing works
Determination of aqueous solubility by heating and equilibration: A technical note
Loftsson, Þ., & Hreinsdóttir, D. (2006) · AAPS PharmSciTech · doi:10.1208/pt070104 · Cited by 105 · see citing works
Chakraborty, S., Shukla, D., Jain, A., Mishra, B., & Singh, S. K. (2009) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2009.03.047 · Cited by 102 · see citing works
Molecular Design for Enhancement of Ocular Penetration
Shirasaki, Y. (2007) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21200 · Cited by 100 · see citing works
Poloxamine-based nanomaterials for drug delivery
Alvarez‐Lorenzo, C. (2010) · Frontiers in Bioscience-Elite · doi:10.2741/e102 · Cited by 99 · see citing works
Self-citationThe ex vivo wettability of soft contact lenses
Tonge, S. R., Jones, L., Goodall, S. C., et al. (2001) · Current Eye Research · doi:10.1076/ceyr.23.1.51.5418 · Cited by 98 · see citing works
Chiappetta, D. A., Facorro, G., Rubin de Celis, E., & Sosnik, A. (2011) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2011.01.017 · Cited by 96 · see citing works
Self-citationDi Tommaso, C., Torriglia, A., Furrer, P., Behar-Cohen, F., Gurny, R., & Möller, M. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.01.004 · Cited by 84 · see citing works
Chiappetta, D. A., Alvarez‐Lorenzo, C., Rey‐Rico, A., et al. (2010) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2010.05.007 · Cited by 81 · see citing works
Self-citationIn-vitro release of diclofenac diethylammonium from lipid-based formulations
Parsaee, S., Sarbolouki, M. N., & Parnianpour, M. (2002) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(02)00238-7 · Cited by 76 · see citing works
Eye drop delivery of nano‐polymeric micelle formulated genes with cornea‐specific promoters
Tong, Y.-C., Chang, S., Liu, C., Kao, W. W. ‐., Huang, C. H., & Liaw, J. (2007) · The Journal of Gene Medicine · doi:10.1002/jgm.1093 · Cited by 71 · see citing works
Controlled release of estradiol solubilized in carbopol/surfactant aggregates
Barreiro-Iglesias, R., Alvarez‐Lorenzo, C., & Concheiro, Á. (2003) · Journal of Controlled Release · doi:10.1016/j.jconrel.2003.08.015 · Cited by 65 · see citing works
Self-citationTopically effective ocular hypotensive acetazolamide and ethoxyzolamide formulations in rabbits
Loftsson, Þ., Friðriksdóttir, H., Stefánsson, E., Thórisdóttir, S., Gudmundsson, Ó. S., & Sigthórsson, T. (1994) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1994.tb03835.x · Cited by 65 · see citing works
Preparation and properties of mixed micelles made of Pluronic polymer and PEG-PE
Li, L., & Tan, Y. B. (2007) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2007.09.053 · Cited by 65 · see citing works
Topical carbonic anhydrase inhibitors
Schoenwald, R. D., Eller, M. G., Dixson, J. A., et al. (1984) · Journal of Medicinal Chemistry · doi:10.1021/jm00372a020 · Cited by 64 · see citing works
Quantitation of drug content in a low dosage formulation by transmission near infrared spectroscopy
Meza, C. P., Santos, M. A., & Romañach, R. J. (2006) · AAPS PharmSciTech · doi:10.1208/pt070129 · Cited by 61 · see citing works
Kadam, Y., Singh, K., Marangoni, D. G., et al. (2010) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2010.08.010 · Cited by 61 · see citing works
Diffusional model for transport rate studies across membranes
Stehle, R. G., & Higuchi, W. I. (1967) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600561040 · Cited by 57 · see citing works
Parekh, P. Y., Singh, K., Marangoni, D. G., & Bahadur, P. (2010) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2010.10.046 · Cited by 52 · see citing works
Cuestas, M. L., Sosnik, A., & Mathet, V. L. (2011) · Molecular Pharmaceutics · doi:10.1021/mp2000132 · Cited by 51 · see citing works
Self-citationInhibition of P-Glycoprotein Pumps by PEO–PPO Amphiphiles: Branched Versus Linear Derivatives
Alvarez‐Lorenzo, C., Rey‐Rico, A., Brea, J. M., et al. (2010) · Nanomedicine · doi:10.2217/nnm.10.53 · Cited by 50 · see citing works
Self-citation2-hydroxypropyl-β-cyclodextrin in topical carbonic anhydrase inhibitor formulations
Loftsson, Þ., Friđriksdóttir, H., Thórisdóttir, S., et al. (1994) · European Journal of Pharmaceutical Sciences · doi:10.1016/0928-0987(94)90001-9 · Cited by 49 · see citing works
Lewis, R. A. (1984) · Archives of Ophthalmology · doi:10.1001/archopht.1984.01040031479027 · Cited by 46 · see citing works
Chiappetta, D. A., Höcht, C., & Sosnik, A. (2010) · Current HIV Research · doi:10.2174/157016210791111142 · Cited by 45 · see citing works
Self-citationCorrositex®, BCOP and HET-CAM as alternative methods to animal experimentation
Cazedey, E. C. L., Carvalho, F. C., Fiorentino, F. A. M., et al. (2009) · Brazilian Journal of Pharmaceutical Sciences · doi:10.1590/s1984-82502009000400021 · Cited by 39 · see citing works
Receptor-based biomimetic NVP/DMA contact lenses for loading/eluting carbonic anhydrase inhibitors
Ribeiro, A. M., Veiga, F., Santos, D. F. G., Torres-Labandeira, J. J., Concheiro, Á., & Alvarez‐Lorenzo, C. (2011) · Journal of Membrane Science · doi:10.1016/j.memsci.2011.08.030 · Cited by 39 · see citing works
Self-citationEller, M. G., Schoenwald, R. D., DIXSON, J. A., et al. (1985) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600740210 · Cited by 39 · see citing works
Effect of additives on the cloud points of two tri-block copolymers in aqueous solution
Lin, X., Xu, J., Wanguo, H., & Sun, D. (2004) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2004.02.008 · Cited by 33 · see citing works
Liu, C. C., Chang, K., & Wang, Y. J. (2009) · Journal of Polymer Research · doi:10.1007/s10965-009-9332-5 · Cited by 26 · see citing works
Alvarez‐Lorenzo, C., Concheiro, Á., & Sosnik, A. (2011) · Cited by 5 · see citing works
Self-citationLippa, E. A. (1991) · Springer eBooks · doi:10.1007/978-1-4899-0750-9_14 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- 8 Lippa, E. A. 1991 Topical carbonic anhydrase inhibitors. In The carbonic anhydrases: cellular physiology and molecular genetics (eds S. J. Dodgson, R. E. Tashian, G. Gros & N. D. Carter), pp. 171-181. New York, NY/ London, UK: Plenum Press.
Cited by
Sorted by citations
Polymeric mixed micelles as nanomedicines: Achievements and perspectives
Cagel, M., Tesan, F. C., Bernabeu, E., Salgueiro, M. J., Zubillaga, M. B., Moretton, M. A., & Chiappetta, D. A. (2017) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2016.12.019 · Cited by 417 · see citing works
Self-citationPolymeric micelles in mucosal drug delivery: challenges towards clinical translation
Sosnik, A., & Menaker Raskin, M. (2015) · Biotechnology Advances · doi:10.1016/j.biotechadv.2015.01.003 · Cited by 154 · see citing works
Self-citationPoloxamer 407/TPGS mixed micelles as promising carriers for cyclosporine ocular delivery
Grimaudo, M. A., Pescina, S., Padula, C., Santi, P., Concheiro, A., Alvarez-Lorenzo, C., & Nicoli, S. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b00939 · Cited by 138 · see citing works
Self-citationYounes, N. F., Abdel-Halim, S. A., & Elassasy, A. I. (2018) · Drug Delivery · doi:10.1080/10717544.2018.1497107 · Cited by 81 · see citing works
Grimaudo, M. A., Pescina, S., Padula, C., Santi, P., Concheiro, A., Alvarez-Lorenzo, C., & Nicoli, S. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1597848 · Cited by 78 · see citing works
Self-citationFahmy, A. M., Hassan, M., El-Setouhy, D. A., Tayel, S. A., & Al-mahallawi, A. M. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.12.013 · Cited by 45 · see citing works
From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics
Sun, M., Wang, J., Fan, W., Wang, K., Wang, Y., Zhang, J., Ding, S., Zhang, C., Feng, Z., Wang, Y.-G., et al. (2025) · Materials today. Bio · doi:10.1016/j.mtbio.2025.102537 · Cited by 7 · see citing works
“The co-micellization of polox-amines upgrades the stability of drug-loaded formulations and allow the modulation of drug loading and release process [157].”
- Authors
- Ribeiro, A., Sosnik, A., Chiappetta, D. A., Veiga, F., Concheiro, A., & Alvarez-Lorenzo, C.
- Affiliations
- Universidade de Santiago de Compostela (ES)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- University of Coimbra (PT)
- Universidad de Santiago de Compostela 3 , ,
- Venue
- Journal of The Royal Society Interface
- Publisher
- The Royal Society
- Published
- 2012-04-04
- Volume
- 9
- Issue
- 74
- Pages
- 2059-2069
- ISSN
- 1742-5662 (ISSN-L)
- 1742-5689
- PMC
- PMC3405752
- OpenAlex
- W2160269316
- Cited by
- 91
- References
- 50
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 6 · 2015: 8 · 2014: 8 · 2013: 5 · 2012: 2
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of The Royal Society Interface (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Chemistry › Organic Chemistry › Surfactants and Colloidal Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- mixed micelles, ethoxzolamide, topical ocular drug delivery, glaucoma treatment, carbonic anhydrase inhibitors, drug solubilization, sustained drug release, critical micelle concentration, cloud point, micellar stability, nanocarriers
- MeSH terms
- Administration, Topical, Animals, Carbonic Anhydrase Inhibitors, Chick Embryo, Chickens, Delayed-Action Preparations, Ethoxzolamide, Ethylenediamines, Glaucoma, Humans, Micelles, Solubility, Time Factors, Chorioallantoic Membrane, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
