{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:13:16Z","timestamp":1777551196967,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>We previously developed two optimized formulations of dexamethasone acetate (DXMa) hydrogels by means of special cubic mixture designs for topical ocular administration. These gels were elaborated with hydroxypropyl-\u03b2-CD (HP\u03b2CD) and hydroxypropyl-\u03b3-CD (HP\u03b3CD) and commercial hydrogels in order to enhance DXMa water solubility and finally DXMa\u2019s ocular bioavailability and transcorneal penetration. The main objective of this study was to characterize them and to evaluate in vitro, ex vivo, and in vivo their safety, biopermanence, and transcorneal permeation. Gels A and B are Newtonian fluids and display a viscosity of 13.2 mPa.s and 18.6 mPa.s, respectively, which increases their ocular retention, according to the in vivo biopermanence study by PET\/CT. These hydrogels could act as corneal absorption promoters as they allow a higher transcorneal permeation of DXMa through porcine excised cornea, compared to DEXAFREE\u00ae and MAXIDEX\u00ae. Cytotoxicity assays showed no cytotoxic effects on human primary corneal epithelial cells (HCE). Furthermore, Gel B is clearly safe for the eye, but the effect of Gel A on the human eye cannot be predicted. Both gels were also stable 12 months at 25 \u00b0C after sterilization by filtration. These results demonstrate that the developed formulations present a high potential for the topical ocular administration of dexamethasone acetate.<\/jats:p>","DOI":"10.3390\/pharmaceutics12080717","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T04:15:31Z","timestamp":1596168931000},"page":"717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery"],"prefix":"10.3390","volume":"12","author":[{"given":"Roseline","family":"Mazet","sequence":"first","affiliation":[{"name":"University Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"},{"name":"Pharmacy Unit, Grenoble University Hospital, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8351-3180","authenticated-orcid":false,"given":"Xurxo","family":"Garc\u00eda-Otero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy, Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain"},{"name":"Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Choisnard","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Wouessidjewe","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Verdoot","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, CNRS, Grenoble INP, LRP, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Bossard","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, CNRS, Grenoble INP, LRP, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-1292","authenticated-orcid":false,"given":"Victoria","family":"D\u00edaz-Tom\u00e9","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy, Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain"},{"name":"Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Blanc-Marquis","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-2253","authenticated-orcid":false,"given":"Francisco-Javier","family":"Otero-Espinar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy, Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7348-7337","authenticated-orcid":false,"given":"Anxo","family":"Fernandez-Ferreiro","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Pharmacy Department, Clinical University Hospital Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabelle","family":"G\u00e8ze","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/aos.12803","article-title":"Topical dexamethasone \u03b3-cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema","volume":"93","author":"Ohira","year":"2015","journal-title":"Act. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ijpharm.2016.11.053","article-title":"Pharmaceutical technology can turn a traditional drug, dexamethasone into a first-line ocular medicine. A global perspective and future trends","volume":"516","year":"2017","journal-title":"Int J. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jconrel.2015.01.009","article-title":"Corticosteroid-loaded biodegradable nanoparticles for prevention of corneal allograft rejection in rats","volume":"201","author":"Pan","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1016\/j.addr.2005.09.004","article-title":"Topical and systemic drug delivery to the posterior segments","volume":"57","author":"Hughes","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1023\/A:1015838215268","article-title":"Effect of 2-hydroxypropyl-beta-cyclodextrin on the ocular absorption of dexamethasone and dexamethasone acetate","volume":"8","author":"Usayapant","year":"1991","journal-title":"Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/0002-9394(78)90249-0","article-title":"Evaluation of dexamethasone acetate as a topical ophthalmic formulation","volume":"86","author":"Leibowitz","year":"1978","journal-title":"Am. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mazet, R., Choisnard, L., Levilly, D., Wouessidjewe, D., and G\u00e8ze, A. (2018). Investigation of combined cyclodextrin and hydrogel formulation for ocular delivery of dexamethasone acetate by means of experimental designs. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10040249"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.clae.2010.01.007","article-title":"Evaluation of the effects on conjunctival tissues of optive eyedrops over one month usage","volume":"33","author":"Guillon","year":"2010","journal-title":"Cont. Lens Anterior Eye"},{"key":"ref_9","first-page":"195","article-title":"Mucoadhesive polymers and their mode of action: A recent update","volume":"7","author":"Chatterjee","year":"2017","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.3109\/03639045.2012.736515","article-title":"Recent advances in ocular drug delivery","volume":"39","author":"Achouri","year":"2013","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/jop.2013.0050","article-title":"Effect of hypotonic 0.18% sodium hyaluronate eyedrops on inflammation of the ocular surface in experimental dry eye","volume":"30","author":"Oh","year":"2014","journal-title":"J. Ocul. Pharm. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1590\/S1984-82502009000100010","article-title":"Development and validation of HPLC method for analysis of dexamethasone acetate in microemulsions","volume":"45","author":"Urban","year":"2009","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Teasdale, A., Elder, D., and Nims, R.W. (2017). Q2(R1) Validation of Analytical Procedures. ICH Quality Guidelines, ICH.","DOI":"10.1002\/9781118971147.ch0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.jpba.2007.04.032","article-title":"Validation of a dissolution method with HPLC analysis for lasofoxifene tartrate low dose tablets","volume":"44","author":"Space","year":"2007","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_15","unstructured":"GERPAC, and SFPC (2013). Methodological Guidelines for Stability Studies of Hospital Pharmaceutical Preparations, [1st ed.]. Available online: https:\/\/www.gerpac.eu\/IMG\/pdf\/guide_stabilite_anglais.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gra\u00e7a, A., Gon\u00e7alves, L.M., Raposo, S., Ribeiro, H.M., and Marto, J. (2018). Useful In vitro techniques to evaluate the mucoadhesive properties of hyaluronic acid-based ocular delivery systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030110"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Silva, M.M., Calado, R., Marto, J., Bettencourt, A., Almeida, A.J., and Gon\u00e7alves, L.M.D. (2017). Chitosan nanoparticles as a mucoadhesive drug delivery system for ocular administration. Mar. Drugs, 15.","DOI":"10.3390\/md15120370"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ijbiomac.2015.11.070","article-title":"Chitosan-based nanoparticles for rosmarinic acid ocular delivery\u2014In vitro tests","volume":"84","author":"Ferreira","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1007\/s13346-016-0330-y","article-title":"Human corneal cell culture models for drug toxicity studies","volume":"6","author":"Vellonen","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"425101","DOI":"10.1088\/1361-6528\/aad7da","article-title":"A potential nanoparticle-loaded in situ gel for enhanced and sustained ophthalmic delivery of dexamethasone","volume":"29","author":"Wen","year":"2018","journal-title":"Nanotechnology"},{"key":"ref_21","unstructured":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011). Guide for the Care and Use of Laboratory Animals, National Academies Press. [8th ed.]. The national academies collection: Reports funded by national institutes of health."},{"key":"ref_22","first-page":"772","article-title":"Positron emission tomography for the development and characterization of corneal permanence of ophthalmic pharmaceutical formulations","volume":"58","author":"Lamas","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cmpb.2010.01.007","article-title":"PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel","volume":"99","author":"Zhang","year":"2010","journal-title":"Comput. Methods Programs Biomed."},{"key":"ref_24","unstructured":"(2019). European Phramacopoeia, EDQM. [9.8th ed.]."},{"key":"ref_25","unstructured":"McEvoy, G.K. (2007). American Society of Health-System Pharmacists. AHFS Drug information 2007, American Society of Health-System Pharmacists."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.2042-7158.1986.tb04611.x","article-title":"A comparison of the effect of viscosity on the precorneal residence of solutions in rabbit and man","volume":"38","author":"Zaki","year":"1986","journal-title":"J. Pharm. Pharmcol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/eye.1990.83","article-title":"Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy","volume":"4","author":"Snibson","year":"1990","journal-title":"Eye"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.carbpol.2016.07.106","article-title":"Optimization of hyaluronan-based eye drop formulations","volume":"153","author":"Salzillo","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_29","unstructured":"Franck, A. (2004). Understanding Rheology of Structured Fluids, TA Instruments. Available online: http:\/\/scholar.google.com\/scholar?hl=en&btnG=Search&q=intitle:Understanding+Rheology+of+Structured+Fluids#2%5Cnhttp:\/\/scholar.google.com\/scholar?hl=en&btnG=Search&q=intitle."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0168-3659(97)00138-7","article-title":"A rheological examination of the mucoadhesive\/mucus interaction: The effect of mucoadhesive type and concentration","volume":"50","author":"Madsen","year":"1998","journal-title":"J. Control. Release"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.addr.2005.07.005","article-title":"The use of mucoadhesive polymers in ocular drug delivery","volume":"57","author":"Ludwig","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_32","unstructured":"OECD (2018). Guideline for the Testing of Chemicals\u2014Short Time Exposure in Vitro Test Method, Organisation for Economic Co-operation and Development. Available online: https:\/\/www.oecd-ilibrary.org\/environment\/test-no-491-short-time-exposure-in-vitro-test-method-for-identifying-i-chemicals-inducing-serious-eye-damage-and-ii-chemicals-not-requiring-classification-for-eye-irritation-or-serious-eye-damage_9789264242432-en."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ijpharm.2007.01.015","article-title":"Study of the relationship between lipid binding properties of cyclodextrins and their effect on the integrity of liposomes","volume":"338","author":"Piel","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.3762\/bjoc.10.308","article-title":"Cyclodextrin\u2013polysaccharide-based, in situ-gelled system for ocular antifungal delivery","volume":"10","author":"Varela","year":"2014","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_35","first-page":"443","article-title":"A different look at corticosteroids","volume":"58","author":"Zoorob","year":"1998","journal-title":"Am. Fam. Physician"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1007\/s11095-016-1903-7","article-title":"Synthesis and characterization of poly(2-hydroxyethylmethacrylate) contact lenses containing chitosan nanoparticles as an ocular delivery system for dexamethasone sodium phosphate","volume":"33","author":"Behl","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1097\/01.ico.0000208815.02120.90","article-title":"Inhibition of inflammatory cytokine production in human corneal cells by dexamethasone, but not cyclosporin","volume":"25","author":"Djalilian","year":"2006","journal-title":"Cornea"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Castro-Balado, A., Mondelo-Garc\u00eda, C., Gonz\u00e1lez-Barcia, M., Zarra-Ferro, I., Otero-Espinar, F.J., Ruibal-Morell, \u00c1., Aguiar, P., and Fern\u00e1ndez-Ferreiro, A. (2019). Ocular biodistribution studies using molecular imaging. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050237"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ejps.2018.04.038","article-title":"Preclinical characterization and clinical evaluation of tacrolimus eye drops","volume":"120","author":"Aguiar","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_40","unstructured":"ICH (2003). Stability testing of new drug substances and products Q1A (R2). Proceedings of the International Conference on Harmonisation, ICH. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-q-1-r2-stability-testing-new-drug-substances-products-step-5_en.pdf."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/8\/717\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:52:59Z","timestamp":1760176379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/8\/717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,30]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["pharmaceutics12080717"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12080717","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,30]]}}}