{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T20:31:09Z","timestamp":1775075469664,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>In situ poloxamer-based gels are increasingly being explored as ocular drug delivery carriers to extend the release of active substances, thereby enhancing bioavailability. The objective of this study was to develop thermally stable in situ gels incorporating balsam poplar bud extract, propolis extract, and p-coumaric acid solution and to evaluate the physicochemical parameters of these gelified eye drops. This research assessed the compatibility of poloxamer-based eye drops with active components, their physicochemical properties, stability post-sterilization and during storage, and the release profiles of the active compounds. Fifteen eye drop formulations were prepared and categorized into three groups based on active components. One of the active components was propolis extract. As an alternative to propolis, eye drops containing the plant precursor, balsam poplar bud extract, were developed. The third group\u2019s active component was p-coumaric acid, a dominant phenolic acid in propolis and balsam poplar bud extracts. The study reported phenolic contents of 76.63 CAE mg\/g for propolis and 83.25 CAE mg\/g for balsam poplar bud aqueous extracts, with balsam poplar bud extracts showing higher SPF values (14.0) compared to propolis (12.7), while p-coumaric acid solution exhibited the highest SPF values (25.5). All eye drops were transparent, with pH values meeting the requirements for ocular drops. Formulations containing 8\u201310% poloxamer 407 met the criteria for in situ gels. All formulations remained stable for 90 days. Conclusion: The study results indicate that the formulated gels possess suitable physicochemical properties, are resistant to applied autoclaving conditions, and exhibit an extended release of active compounds with an increase in poloxamer content.<\/jats:p>","DOI":"10.3390\/gels10030161","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:50:22Z","timestamp":1708498222000},"page":"161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Application of Poloxamer for In Situ Eye Drop Modeling by Enrichment with Propolis and Balsam Poplar Buds Phenolic Compounds"],"prefix":"10.3390","volume":"10","author":[{"given":"Monika","family":"Jokubaite","sequence":"first","affiliation":[{"name":"Department of Drug Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, Sukileliai Avenue 13, LT-50162 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mindaugas","family":"Marksa","sequence":"additional","affiliation":[{"name":"Department of Analytical & Toxicological Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, Sukileliai Avenue 13, LT-50162 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Ramanauskiene","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Lithuanian University of Health Sciences, Sukileliai Avenue 13, LT-50162 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2174\/1389557516666151120114605","article-title":"The Role Oxidative Stress in the Pathogenesis of Eye Diseases: Current Status and a Dual Role of Physical Activity","volume":"16","author":"Kruk","year":"2015","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4103\/1319-4534.337849","article-title":"Dry Eye Syndrome Risk Factors: A Systemic Review","volume":"35","author":"Hasan","year":"2021","journal-title":"Saudi J. Ophthalmol. Off. J. Saudi Ophthalmol. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2020.01.057","article-title":"Advances and Limitations of Drug Delivery Systems Formulated as Eye Drops","volume":"321","author":"Jumelle","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/1120672118769776","article-title":"Novel Drug Delivery Systems for Ocular Therapy: With Special Reference to Liposomal Ocular Delivery","volume":"29","author":"Bhattacharjee","year":"2019","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Choi, S.W., and Kim, J. (2018). Therapeutic Contact Lenses with Polymeric Vehicles for Ocular Drug Delivery: A Review. Materials, 11.","DOI":"10.3390\/ma11071125"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1208\/s12249-021-01977-0","article-title":"Review of Approaches for Increasing Ophthalmic Bioavailability for Eye Drop Formulations","volume":"22","author":"Lanier","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"337","DOI":"10.22270\/jddt.v9i1.2231","article-title":"Ocular in Situ Gel: An Overview","volume":"9","author":"Majeed","year":"2019","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5497\/wjp.v2.i2.47","article-title":"Ocular Drug Delivery Systems: An Overview","volume":"2","author":"Patel","year":"2013","journal-title":"World J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6988","DOI":"10.1039\/D0PY00919A","article-title":"Advancing the Stimuli Response of Polymer-Based Drug Delivery Systems for Ocular Disease Treatment","volume":"11","author":"Nguyen","year":"2020","journal-title":"Polym. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e05365","DOI":"10.1016\/j.heliyon.2020.e05365","article-title":"In Situ Ophthalmic Gel Forming Systems of Poloxamer 407 and Hydroxypropyl Methyl Cellulose Mixtures for Sustained Ocular Delivery of Chloramphenicole: Optimization Study by Factorial Design","volume":"6","author":"Kurniawansyah","year":"2020","journal-title":"Heliyon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajps.2018.04.008","article-title":"Research Progress of In-Situ Gelling Ophthalmic Drug Delivery System","volume":"14","author":"Wu","year":"2019","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.lfs.2019.02.029","article-title":"Glaucoma: Current Treatment and Impact of Advanced Drug Delivery Systems","volume":"221","author":"Yadav","year":"2019","journal-title":"Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"126190","DOI":"10.1016\/j.cej.2020.126190","article-title":"Multifunctional Glutathione-Dependent Hydrogel Eye Drops with Enhanced Drug Bioavailability for Glaucoma Therapy","volume":"402","author":"Lai","year":"2020","journal-title":"Chem. Eng. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tox.2008.09.011","article-title":"Protective Effect of 4-Coumaric Acid from UVB Ray Damage in the Rabbit Eye","volume":"255","author":"Lodovici","year":"2009","journal-title":"Toxicology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chavda, V.P., Chaudhari, A.Z., Teli, D., Balar, P., and Vora, L. (2023). Propolis and Their Active Constituents for Chronic Diseases. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020259"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s10886-016-0708-9","article-title":"Selective Behaviour of Honeybees in Acquiring European Propolis Plant Precursors","volume":"42","author":"Isidorov","year":"2016","journal-title":"J. Chem. Ecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jphotobiol.2018.01.028","article-title":"The Photoprotective and Anti-Inflammatory Activity of Red Propolis Extract in Rats","volume":"180","author":"Batista","year":"2018","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1007\/s11101-022-09816-1","article-title":"Propolis: Chemical Diversity and Challenges in Quality Control","volume":"21","author":"Kasote","year":"2022","journal-title":"Phytochem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Stanciauskaite, M., Marksa, M., Rimkiene, L., and Ramanauskiene, K. (2022). Evaluation of Chemical Composition, Sun Protection Factor and Antioxidant Activity of Lithuanian Propolis and Its Plant Precursors. Plants, 11.","DOI":"10.3390\/plants11243558"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"712","DOI":"10.3390\/medicina45090093","article-title":"Analysis of Content of Phenolic Acids in Lithuanian Propolis Using High-Performance Liquid Chromatography Technique","volume":"45","author":"Ramanauskiene","year":"2009","journal-title":"Medicina"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Stanciauskaite, M., Marksa, M., Babickaite, L., Majiene, D., and Ramanauskiene, K. (2021). Comparison of Ethanolic and Aqueous Populus Balsamifera L. Bud Extracts by Different Extraction Methods: Chemical Composition, Antioxidant and Antibacterial Activities. Pharmaceuticals, 14.","DOI":"10.3390\/ph14101018"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.phytol.2023.09.013","article-title":"Optimization of Propolis Extraction with Natural Deep Eutectic Solvents Using Central Composite Design","volume":"58","author":"Alpat","year":"2023","journal-title":"Phytochem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Stanciauskaite, M., Marksa, M., Liaudanskas, M., Ivanauskas, L., Ivaskiene, M., and Ramanauskiene, K. (2021). Extracts of Poplar Buds (Populus balsamifera L., Populus nigra L.) and Lithuanian Propolis: Comparison of Their Composition and Biological Activities. Plants, 10.","DOI":"10.3390\/plants10050828"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.3748\/wjg.v16.i27.3377","article-title":"Galangin Induces Apoptosis of Hepatocellular Carcinoma Cells via the Mitochondrial Pathway","volume":"16","author":"Zhang","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/S0367-326X(02)00187-9","article-title":"Antioxidant Activity of Propolis: Role of Caffeic Acid Phenethyl Ester and Galangin","volume":"73","author":"Russo","year":"2002","journal-title":"Fitoterapia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1383-5742(01)00054-0","article-title":"Anti-Genotoxicity of Galangin as a Cancer Chemopreventive Agent Candidate","volume":"488","author":"Heo","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kis, B., Avram, S., Pavel, I.Z., Lombrea, A., Buda, V., Dehelean, C.A., Soica, C., Yerer, M.B., Bojin, F., and Folescu, R. (2020). Recent Advances Regarding the Phytochemical and Therapeutic Uses of Populus nigra L. Buds. Plants, 9.","DOI":"10.3390\/plants9111464"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kurek-G\u00f3recka, A., G\u00f3recki, M., Rzepecka-Stojko, A., Balwierz, R., and Stojko, J. (2020). Bee Products in Dermatology and Skin Care. Molecules, 25.","DOI":"10.3390\/molecules25030556"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.foodchem.2017.07.133","article-title":"Theoretical Studies on the Antioxidant Activity of Pinobanksin and Its Ester Derivatives: Effects of the Chain Length and Solvent","volume":"240","author":"Zheng","year":"2018","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.sajb.2020.10.022","article-title":"Investigation of the Anti-Inflammatory and Antioxidant Activities of Luteolin, Kaempferol, Apigenin and Quercetin","volume":"137","author":"Tian","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0891-5849(92)90184-I","article-title":"Antioxidant Potential of Ferulic Acid","volume":"13","author":"Graf","year":"1992","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.bbagen.2010.11.004","article-title":"Evaluation of Antioxidant Activity of Vanillin by Using Multiple Antioxidant Assays","volume":"1810","author":"Tai","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s00210-017-1407-y","article-title":"Anticancer Activity of Salicin and Fenofibrate","volume":"390","author":"Sabaa","year":"2017","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/ptr.3095","article-title":"p-Coumaric Acid Not Only Inhibits Human Tyrosinase Activity in Vitro but Also Melanogenesis in Cells Exposed to UVB","volume":"24","author":"An","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1080\/10715760802510077","article-title":"Hydrocaffeic and p-Coumaric Acids, Natural Phenolic Compounds, Inhibit UV-B Damage in WKD Human Conjunctival Cells in Vitro and Rabbit Eye in Vivo","volume":"42","author":"Larrosa","year":"2008","journal-title":"Free Radic. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cassano, R., Di Gioia, M.L., and Trombino, S. (2021). Gel-Based Materials for Ophthalmic Drug Delivery. Gels, 7.","DOI":"10.3390\/gels7030130"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.drudis.2019.05.036","article-title":"Poloxamer-Based in Situ Gelling Thermoresponsive Systems for Ocular Drug Delivery Applications","volume":"24","author":"Soliman","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"116268","DOI":"10.1016\/j.carbpol.2020.116268","article-title":"Thermoresponsive Systems Composed of Poloxamer 407 and HPMC or NaCMC: Mechanical, Rheological and Sol-Gel Transition Analysis","volume":"240","author":"Cook","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/JAMPS\/2017\/33924","article-title":"Quality Control Tests for Ophthalmic Pharmaceuticals: Pharmacopoeial Standards and Specifications","volume":"14","author":"Uddin","year":"2017","journal-title":"J. Adv. Med. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1167\/tvst.12.1.27","article-title":"Local Ugandan Production of Stable 0.2% Chlorhexidine Eye Drops","volume":"12","author":"Picken","year":"2023","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_41","first-page":"845","article-title":"The Influence of Excipients on Stability of Viscous Eye Drops with Dexpanthenol in Pharmaceutical Practice","volume":"76","author":"Vesna","year":"2019","journal-title":"Acta Pol. Pharm.-Drug Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2147\/OPTO.S281601","article-title":"Impact of Ocular Surface Temperature on Tear Characteristics: Current Insights","volume":"13","author":"Shah","year":"2021","journal-title":"Clin. Optom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100046","DOI":"10.1016\/j.aopr.2022.100046","article-title":"Microbial Contamination of Multiple-Dose Preservative-Free Hospital Ophthalmic Preparations in a Tertiary Care Hospital","volume":"2","author":"Chantra","year":"2022","journal-title":"Adv. Ophthalmol. Pract. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zieli\u0144ska, A., Soles, B.B., Lopes, A.R., Vaz, B.F., Rodrigues, C.M., Alves, T.F.R., Klensporf-Pawlik, D., Durazzo, A., Lucarini, M., and Severino, P. (2020). Nanopharmaceuticals for Eye Administration: Sterilization, Depyrogenation and Clinical Applications. Biology, 9.","DOI":"10.3390\/biology9100336"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40780-019-0154-2","article-title":"Physical, Chemical, and Microbiological Stability Study of Diluted Atropine Eye Drops","volume":"5","author":"Saito","year":"2019","journal-title":"J. Pharm. Health Care Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0076-6879(99)99017-1","article-title":"[14] Analysis of Total Phenols and Other Oxidation Substrates and Antioxidants by Means of Folin-Ciocalteu Reagent","volume":"Volume 299","author":"Singleton","year":"1999","journal-title":"Oxidants and Antioxidants Part A"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e00390","DOI":"10.1016\/j.heliyon.2017.e00390","article-title":"Thermogelling Properties of Purified Poloxamer 407","volume":"3","author":"Fakhari","year":"2017","journal-title":"Heliyon"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1080\/13102818.2017.1288073","article-title":"Phytochemical Analysis and Evaluation of Antioxidant and Photoprotective Activities of Extracts from Flowers of Bromelia Laciniosa (Bromeliaceae)","volume":"31","author":"Ferraz","year":"2017","journal-title":"Biotechnol. Biotechnol. Equip."},{"key":"ref_49","first-page":"121","article-title":"Determina\u00e7\u00e4o Do Fator de Prote\u00e7\u00e4o Solar Por Espectrofotometria","volume":"61","author":"Breder","year":"1986","journal-title":"An. Bras. Dermatol"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/j.1751-1097.1979.tb07090.x","article-title":"A comparison of In Vivo and In Vitro testing of sunscreening formulas","volume":"29","author":"Sayre","year":"1979","journal-title":"Photochem. Photobiol."}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/10\/3\/161\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:02:23Z","timestamp":1760104943000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/10\/3\/161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,21]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["gels10030161"],"URL":"https:\/\/doi.org\/10.3390\/gels10030161","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,21]]}}}