{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:54:00Z","timestamp":1792079640154,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/02\/X\/NZ7\/02622"],"award-info":[{"award-number":["2018\/02\/X\/NZ7\/02622"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005297","name":"Uniwersytet Medyczny w Bialymstoku","doi-asserted-by":"publisher","award":["N\/ST\/ZB\/18\/005\/2215"],"award-info":[{"award-number":["N\/ST\/ZB\/18\/005\/2215"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and seem to be a very promising alternative to conventional oral formulations. Hence, in this study, mucoadhesive buccal films based on the alginate and its oligosaccharide oligomer composed predominantly of mannuronic acid for the administration of posaconazole-antifungal drug from the azole group were developed. As the polymer gelation method, a relatively new freeze-thaw technique was chosen. All prepared formulations were examined for pharmaceutical tests, swelling, mechanical, and mucoadhesive properties. In addition, the influence of sodium alginate (ALG) and alginate oligosaccharides (OLG) on POS antifungal activity on Candida species was performed. It was observed that film formulation containing 1% ALG and 1% OLG (F2) was characterized by optimal mucoadhesive and swelling properties and prolonged drug release up to 5 h. Additionally, it was shown that OLG affected the growth reduction of all tested Candida spp. The obtained data has opened the way for future research for developing OLG-based dosage forms, which might increase the activity of antifungal drugs.<\/jats:p>","DOI":"10.3390\/md17120692","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T11:22:51Z","timestamp":1575890571000},"page":"692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-5350","authenticated-orcid":false,"given":"Marta","family":"Szekalska","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Bia\u0142ystok, Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Wr\u00f3blewska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Bia\u0142ystok, Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Trofimiuk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Bia\u0142ystok, Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-1779","authenticated-orcid":false,"given":"Anna","family":"Basa","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Bia\u0142ystok, Cio\u0142kowskiego 1K, 15-245 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1013-610X","authenticated-orcid":false,"given":"Katarzyna","family":"Winnicka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Medical University of Bia\u0142ystok, Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fmicb.2017.00036","article-title":"Antifungal therapy: New advances in the understanding and treatment of mycosis","volume":"8","author":"Scorzoni","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5503","DOI":"10.1128\/AAC.00802-12","article-title":"Multicenter study of posaconazole therapeutic drug monitoring: Exposure-response relationship and factors affecting concentration","volume":"56","author":"Dolton","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s40204-017-0077-7","article-title":"New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate","volume":"6","author":"Salehi","year":"2017","journal-title":"Prog. Biomater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1155\/2016\/7697031","article-title":"Alginate: Current use and future perspectives in pharmaceutical and biomedical applications","volume":"2016","author":"Szekalska","year":"2016","journal-title":"Int. J. Polym. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cardoso, M.J., Costa, R.R., and Mano, J.F. (2016). Marine origin polysaccharides in drug delivery systems. Mar. Drugs, 14.","DOI":"10.3390\/md14020034"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Han, Z.L., Yang, M., Fu, X.D., Chen, M., Su, Q., Zhao, Y.H., and Mou, H.J. (2019). Evaluation of prebiotic potential of three marine algae oligosaccharides from enzymatic hydrolysis. Mar. Drugs, 17.","DOI":"10.3390\/md17030173"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00762-17","DOI":"10.1128\/AAC.00762-17","article-title":"A low-molecular-weight alginate oligosaccharide disrupts pseudomonal microcolony formation and enhances antibiotic effectiveness","volume":"61","author":"Pritchard","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"T\u00f8ndervik, A., Sletta, H., Klinkenberg, G., Emanuel, C., Powell, L.C., Pritchard, M.F., Khan, S., Craine, K.M., Ons\u00f8yen, E., and Rye, P.D. (2014). Alginate oligosaccharides inhibit fungal cell growth and potentiate the activity of antifungals against Candida and Aspergillus spp.. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0112518"},{"key":"ref_9","first-page":"97","article-title":"Potential use of alginate-based carriers as antifungal delivery system","volume":"8","author":"Lopes","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.carbpol.2016.04.047","article-title":"Freeze-thaw induced gelation of alginates","volume":"148","author":"Zhao","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gurikov, P., and Smirnova, I. (2018). Non-conventional methods for gelation of alginate. Gels, 4.","DOI":"10.3390\/gels4010014"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Dorado, R., L\u00f3pez-Iglesias, C., Garc\u00eda-Gonz\u00e1lez, C.A., Auriemma, G., Aquino, R.P., and Del Gaudio, P. (2019). Design of aerogels, cryogels and xerogels of alginate: Effect of molecular weight, gelation conditions and drying method on particles\u2019 micromeritics. Molecules, 24.","DOI":"10.3390\/molecules24061049"},{"key":"ref_13","unstructured":"Council of Europe (2016). The European Pharmacopeia, Council of Europe. [9th ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"461","DOI":"10.4103\/0972-124X.118317","article-title":"Salivary pH: A diagnostic biomarker","volume":"17","author":"Baliga","year":"2013","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ajps.2016.05.004","article-title":"Thin films as an emerging platform for drug delivery","volume":"11","author":"Karki","year":"2016","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_16","first-page":"213","article-title":"Preparation and pharmaceutical evaluation of glibenclamide slow release mucoadhesive buccal film","volume":"9","author":"Tavakoli","year":"2014","journal-title":"Res. Pharm. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.foodhyd.2018.03.014","article-title":"Physicochemical properties of alginate-based films: Effect of ionic cross-linking and mannuronic and guluronic acid ratio","volume":"81","author":"Costa","year":"2018","journal-title":"Food Hydrocoll."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"B\u00eersan, M., Apostu, M., Todoran, N., Antonoaea, P., Rusu, A., and Ciurba, A. (2018). Development of dermal films containing miconazole nitrate. Molecules, 23.","DOI":"10.3390\/molecules23071640"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.carbpol.2010.02.002","article-title":"Plasticity of hot air-dried mannuronate- and guluronate-rich alginate films","volume":"81","author":"Ashikin","year":"2010","journal-title":"Carbohydr. Polym."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/j.1365-2621.2011.02897.x","article-title":"Tensile and water vapour properties of calcium-crosslinked alginate-cashew tree gum films","volume":"47","author":"Azeredo","year":"2012","journal-title":"J. Food Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liang, H., Li, S., Lu, Y., and Yang, T. (2018). Reliability study on FRP composites exposed to wet-dry cycles. Appl. Sci., 8.","DOI":"10.3390\/app8060892"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.ijpharm.2014.12.032","article-title":"Ink-jet printing versus solvent casting to prepare oral films: Effect on mechanical properties and physical stability","volume":"2","author":"Buanz","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2174\/1567201811666140924124722","article-title":"Mucoadhesive polymeric platform for drug delivery; a comprehensive review","volume":"12","author":"Agarwal","year":"2015","journal-title":"Curr. Drug Deliv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ijpharm.2010.01.008","article-title":"Characterisation of lyophilised wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces","volume":"389","author":"Boateng","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1208\/s12249-014-0237-1","article-title":"An investigation and characterization on alginate hydrogel dressing loaded with metronidazole prepared by combined inotropic gelation and freeze-thawing cycles for controlled release","volume":"16","author":"Sarheed","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fennel, E., and Huyghe, J.M. (2019). Chemically responsive hydrogel deformation mechanics: A review. Molecules, 24.","DOI":"10.3390\/molecules24193521"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4103\/0975-7406.76478","article-title":"Mucoadhesive drug delivery systems","volume":"3","author":"Shaikh","year":"2011","journal-title":"J. Pharm. Bioallied. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Amemiya, T., Nakamura, T., Yamamoto, T., Kinoshita, S., and Kanamura, N. (2015). Autologous transplantation of oral mucosal epithelial cell sheets cultured on an amniotic membrane substrate for intraoral mucosal defects. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125391"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1021\/bm501832y","article-title":"Biophysical analysis of the molecular interactions between polysaccharides and mucin","volume":"16","author":"Menchicchi","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.2147\/DDDT.S150774","article-title":"Risperidone mucoadhesive buccal tablets: Formulation design, optimization and evaluation","volume":"11","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nehme, H., Saulnier, P., Ramadan, A.A., Cassisa, V., Guillet, C., Eveillard, M., and Umerska, A. (2018). Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0189950"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Pishnamazi, M., Hafizi, H., Shirazian, S., Culebras, M., Walker, G.M., and Collins, M.N. (2019). Design of controlled release system for paracetamol based on modified lignin. Polymers, 11.","DOI":"10.20944\/preprints201905.0297.v1"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Szekalska, M., Sosnowska, K., Zakrzeska, A., Kasacka, I., Lewandowska, A., and Winnicka, K. (2017). The influence of chitosan cross-linking on the properties of alginate microparticles with metformin hydrochloride\u2014In vitro and in vivo evaluation. Molecules, 22.","DOI":"10.3390\/molecules22010182"},{"key":"ref_34","first-page":"197","article-title":"Evaluation of polymeric films for buccal drug delivery","volume":"64","author":"Skulason","year":"2009","journal-title":"Pharmazie"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3109\/10717544.2013.779331","article-title":"Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: A potential approach for delivery of drugs having high first-pass metabolism","volume":"20","author":"Rana","year":"2013","journal-title":"Drug Deliv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0928-0987(01)00095-1","article-title":"Modeling and comparison of dissolution profiles","volume":"13","author":"Costa","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4103\/0975-7406.76463","article-title":"Differential scanning calorimetry: An invaluable tool for a detailed thermodynamic characterization of macromolecules and their interactions","volume":"3","author":"Gill","year":"2011","journal-title":"J. Pharm. Bioallied. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s10924-008-0097-4","article-title":"Preparation of alginic acid and metal alginate from algae and their comparative study","volume":"16","author":"Pathak","year":"2008","journal-title":"J. Polym. Environ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1080\/03639045.2016.1275667","article-title":"Preparation and evaluation of posaconazole-loaded enteric microparticles in rats","volume":"43","author":"Yang","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1021\/mp800042d","article-title":"Amorphous compositions using concentration enhancing polymers for improved bioavailability of itraconazole","volume":"5","author":"DiNunzio","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"015006","DOI":"10.1088\/1748-6041\/7\/1\/015006","article-title":"Acombined effect of freeze-thaw cycles and polymer concentration on the structure and mechanical properties of transparent PVA gels","volume":"7","author":"Gupta","year":"2012","journal-title":"Biomed. Mater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44731","DOI":"10.1038\/srep44731","article-title":"The antimicrobial effects of the alginate oligomer OligoG CF-5\/20 are independent of direct bacterial cell membrane disruption","volume":"7","author":"Powell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_43","unstructured":"Rex, J.H. (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical & Laboratory Standards Institute. [3rd ed.]. CLSI DocumentM27-A3."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"825203","DOI":"10.1155\/2015\/825203","article-title":"Antiviral potential of algae polysaccharides isolated from marine sources: A review","volume":"2015","author":"Ahmadi","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ye, J., Ma, D., Qin, W., and Liu, Y. (2018). Physical and antibacterial properties of sodium alginate-sodium carboxymethylcellulose films containing Lactococcus lactis. Molecules, 23.","DOI":"10.3390\/molecules23102645"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15","DOI":"10.14227\/DT180311P15","article-title":"Simulated biological fluids with possible application in dissolution testing","volume":"3","author":"Marques","year":"2011","journal-title":"Dissolution Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20277","DOI":"10.3390\/ijms160920277","article-title":"The effect of cationic polyamidoamine dendrimers on physicochemical characteristics of hydrogels with erythromycin","volume":"16","author":"Wroblewska","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3390\/pharmaceutics4040551","article-title":"Development of a taste-masked orodispersible film containing dimenhydrinate","volume":"4","author":"Preis","year":"2012","journal-title":"Pharmaceutics"},{"key":"ref_49","first-page":"702963","article-title":"Formulation development of mouth dissolving film of etoricoxib for pain management","volume":"2015","author":"Senthilkumar","year":"2015","journal-title":"Adv. Pharm."},{"key":"ref_50","first-page":"1287","article-title":"Assessment of guar and xanthan gum based floating drug delivery system containing mefenamic acid","volume":"5","author":"Kaur","year":"2016","journal-title":"Acta Pol. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0378-5173(95)04416-7","article-title":"In vitro and in vivo nasal mucoadhesion of some water-soluble polymers","volume":"134","author":"Nakamura","year":"1996","journal-title":"Int. J. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tang, P.H. (2017). Determination of posaconazole in plasma\/serum by high-performance liquid chromatography with fluorescence detection. Separations, 4.","DOI":"10.3390\/separations4020016"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cansizoglu, M.F., Tamer, Y.T., Farid, M., Koh, A.Y., and Toprak, E. (2019). Rapid ultrasensitive detection platform for antimicrobial susceptibility testing. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000291"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/12\/692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:39Z","timestamp":1760190039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/12\/692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["md17120692"],"URL":"https:\/\/doi.org\/10.3390\/md17120692","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,9]]}}}