{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T21:49:53Z","timestamp":1781214593000,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"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":["2014\/15\/D\/ST4\/02770"],"award-info":[{"award-number":["2014\/15\/D\/ST4\/02770"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Low water solubility frequently compromises the therapeutic efficacy of drugs and other biologically active molecules. Here, we report on coacervate polysaccharide nanoparticles (CPNs) that can transport and release a model hydrophobic drug, piroxicam, to the cells in response to changes in temperature. The proposed, temperature-responsive drug delivery system is based on ionic derivatives of natural polysaccharides\u2014curdlan and hydroxypropyl cellulose. Curdlan was modified with trimethylammonium groups, while the anionic derivative of hydroxypropyl cellulose was obtained by the introduction of styrenesulfonate groups. Thermally responsive nanoparticles of spherical shape and average hydrodynamic diameter in the range of 250\u2013300 nm were spontaneously formed in water from the obtained ionic polysaccharides as a result of the coacervation process. Their morphology was visualized using SEM and AFM. The size and the surface charge of the obtained objects could be tailored by adjusting the polycation\/polyanion ratio. Piroxicam (PIX) was effectively entrapped inside the nanoparticles. The release profile of the drug from the CPNs-PIX was found to be temperature-dependent in the range relevant for biomedical applications.<\/jats:p>","DOI":"10.3390\/ijms21249664","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T11:42:09Z","timestamp":1608291729000},"page":"9664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Coacervate Thermoresponsive Polysaccharide Nanoparticles as Delivery System for Piroxicam"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-5297","authenticated-orcid":false,"given":"Dorota","family":"Lachowicz","sequence":"first","affiliation":[{"name":"Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Kaczy\u0144ska","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-8059","authenticated-orcid":false,"given":"Anna","family":"Bodzon-Kulakowska","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Biochemistry, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-6240","authenticated-orcid":false,"given":"Anna","family":"Karewicz","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-5673","authenticated-orcid":false,"given":"Roma","family":"Wirecka","sequence":"additional","affiliation":[{"name":"Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059 Krakow, Poland"},{"name":"Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9759-4372","authenticated-orcid":false,"given":"Micha\u0142","family":"Szuwarzy\u0144ski","sequence":"additional","affiliation":[{"name":"Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6662-7621","authenticated-orcid":false,"given":"Szczepan","family":"Zapotoczny","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.2147\/IJN.S127683","article-title":"A review of drug delivery systems based on nanotechnology and green chemistry: Green nanomedicine","volume":"12","author":"Jahangirian","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.nano.2011.05.016","article-title":"Nanoparticles: A boon to drug delivery, therapeutics, diagnostics and imaging","volume":"8","author":"Parveen","year":"2012","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-981-13-9833-9_9","article-title":"Nanoparticles for drug delivery","volume":"Volume 118","author":"Tariq","year":"2019","journal-title":"Advanced Structured Materials"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40824-020-0184-8","article-title":"Emerging role of nanosuspensions in drug delivery systems","volume":"24","author":"Jacob","year":"2020","journal-title":"Biomater. Res."},{"key":"ref_6","first-page":"1","article-title":"Nanoparticle-directed and ionically forced polyphosphate coacervation: A versatile and reversible core\u2013shell system for drug delivery","volume":"10","author":"Tolba","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.colsurfb.2010.07.006","article-title":"Kinetics of coacervation transition versus nanoparticle formation in chitosan-sodium tripolyphosphate solutions","volume":"81","author":"Kaloti","year":"2010","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dutta, L.P., and Das, M. (2015). Coacervation\u2014A Method for Drug Delivery, Springer.","DOI":"10.1007\/978-81-322-2256-9_35"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1039\/C9SM00372J","article-title":"Design rules for encapsulating proteins into complex coacervates","volume":"15","author":"Perry","year":"2019","journal-title":"Soft Matter"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1039\/C3SC52368C","article-title":"Fluidity and water in nanoscale domains define coacervate hydrogels","volume":"5","author":"Ortony","year":"2014","journal-title":"Chem. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1905220","DOI":"10.1002\/adfm.201905220","article-title":"Biologization of Allogeneic Bone Grafts with Polyphosphate: A Route to a Biomimetic Periosteum","volume":"29","author":"Wang","year":"2019","journal-title":"Adv. Funct. Mater."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xia, J., and Dubin, P.L. (1994). Protein-polyelectrolyte complexes. Macromolecular Complexes in Chemistry and Biology, Springer.","DOI":"10.1007\/978-3-642-78469-9_15"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0268-005X(99)00032-6","article-title":"Complex coacervation between \u03b2-lactoglobulin and acacia gum in aqueous medium","volume":"13","author":"Schmitt","year":"1999","journal-title":"Food Hydrocoll."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jconrel.2008.01.015","article-title":"Injectable, thermo-reversible and complex coacervate combination gels for protein drug delivery","volume":"127","author":"Jin","year":"2008","journal-title":"J. Control. Release"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/adhm.201300155","article-title":"Hydroxypropyl Cellulose Methacrylate as a Photo-Patternable and Biodegradable Hybrid Paper Substrate for Cell Culture and Other Bioapplications","volume":"3","author":"Qi","year":"2014","journal-title":"Adv. Healthc. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1039\/C9SM00093C","article-title":"Hydroxypropyl cellulose as a green polymer for thermo-responsive aqueous foams","volume":"15","author":"Braunschweig","year":"2019","journal-title":"Soft Matter"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"126018","DOI":"10.1016\/j.foodchem.2019.126018","article-title":"Thermal gelling properties and structural properties of myofibrillar protein including thermo-reversible and thermo-irreversible curdlan gels","volume":"311","author":"Jiang","year":"2020","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110379","DOI":"10.1016\/j.msec.2019.110379","article-title":"Dimethylaminoethyl modified curdlan nanoparticles for targeted siRNA delivery to macrophages","volume":"108","author":"Venkatachalam","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.intimp.2016.07.013","article-title":"Curdlan activates dendritic cells through dectin-1 and toll-like receptor 4 signaling","volume":"39","author":"Kim","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5055","DOI":"10.4049\/jimmunol.1501158","article-title":"Dectin-1 Activation by a Natural Product \u03b2-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype","volume":"195","author":"Liu","year":"2015","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-019-0760-3","article-title":"Tumor-associated macrophages in tumor metastasis: Biological roles and clinical therapeutic applications","volume":"12","author":"Lin","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_22","first-page":"690","article-title":"Dectin-1 agonist curdlan modulates innate immunity to Aspergillus fumigatus in human corneal epithelial cells","volume":"8","author":"Zhu","year":"2015","journal-title":"Int. J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1177\/112067210301300605","article-title":"Effectiveness and tolerance of piroxicam 0.5% and diclofenac sodium 0.1% in controlling inflammation after cataract surgery","volume":"13","author":"Scuderi","year":"2003","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5843","DOI":"10.2147\/DDDT.S84849","article-title":"The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors","volume":"9","author":"Campione","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.21873\/anticanres.11506","article-title":"Synergistic Effect of Carboplatin and Piroxicam on Two Bladder Cancer Cell Lines","volume":"37","author":"Silva","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.carbpol.2015.01.050","article-title":"Cationic curdlan: Synthesis, characterization and application of quaternary ammonium salts of curdlan","volume":"123","author":"Suflet","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.carbpol.2010.06.027","article-title":"New cationic hydrophilic and amphiphilic polysaccharides synthesized by one pot procedure","volume":"82","author":"Nichifor","year":"2010","journal-title":"Carbohydr. Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1021\/bm060436s","article-title":"Synthesis and physicochemical and dynamic mechanical properties of a water-soluble chitosan derivative as a biomaterial","volume":"7","author":"Cho","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.ijbiomac.2020.05.155","article-title":"Spectroscopic studies on the temperature-dependent molecular arrangements in hybrid chitosan\/1,3-\u03b2-D-glucan polymeric matrices","volume":"159","author":"Gieroba","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ijbiomac.2012.10.010","article-title":"Effect of nitrogen source on curdlan production by Alcaligenes faecalis ATCC","volume":"52","author":"Jiang","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_31","unstructured":"Beamson, G., Briggs, D., and Chichester, W. (1992). The Scienta ESCA300 Database, John Wiley & Sons."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1016\/j.eurpolymj.2013.02.012","article-title":"Self-organized thermo-responsive hydroxypropyl cellulose nanoparticles for curcumin delivery","volume":"49","author":"Bielska","year":"2013","journal-title":"Eur. Polym. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1562\/0031-8655(2002)0760127DLBCOP2.0.CO2","article-title":"Do Liposome-binding Constants of Porphyrins Correlate with Their Measured and Predicted Partitioning Between Octanol and Water?","volume":"76","author":"Pandian","year":"2007","journal-title":"Photochem. Photobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0378-5173(92)90282-7","article-title":"Preparation of drug: Hydroxypropylcyclodextrin complexes by a method using ethanol or aqueous ammonium hydroxide as co-solubilizers","volume":"80","author":"Pitha","year":"1992","journal-title":"Int. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1295\/polymj.13.517","article-title":"Binding of Organic Solutes to a Polymer Containing Pendant Sugar Groups","volume":"13","author":"Kobayashi","year":"1981","journal-title":"Polym. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Aricov, L., Angelescu, D.G., B\u0103ran, A., Leontie\u015f, A.R., Popa, V.T., Precupa\u015f, A., Sandu, R., St\u00eeng\u0103, G., and Anghel, D.-F. (2019). Interaction of piroxicam with bovine serum albumin investigated by spectroscopic, calorimetric and computational molecular methods. J. Biomol. Struct. Dyn., 1\u201313.","DOI":"10.1080\/07391102.2019.1645733"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11094-012-0803-3","article-title":"Piroxicam ex vivo release kinetics from zein\/pectin delivery systems","volume":"46","author":"Bobokalonov","year":"2012","journal-title":"Pharm. Chem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ijpharm.2010.10.037","article-title":"Elaborations on the Higuchi model for drug delivery","volume":"418","author":"Paul","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0168-3659(87)90034-4","article-title":"A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs","volume":"5","author":"Ritger","year":"1987","journal-title":"J. Control. Release"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0378-5173(89)90306-2","article-title":"A simple equation for the description of solute release. III. Coupling of diffusion and relaxation","volume":"57","author":"Peppas","year":"1989","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpharm.2005.10.044","article-title":"On the use of the Weibull function for the discernment of drug release mechanisms","volume":"309","author":"Papadopoulou","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ijpharm.2009.10.021","article-title":"\u201cSmart\u201d alginate-hydroxypropylcellulose microbeads for controlled release of heparin","volume":"385","author":"Karewicz","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijpharm.2017.02.048","article-title":"Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity","volume":"521","author":"Monnery","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.colsurfb.2013.03.059","article-title":"Curcumin-containing liposomes stabilized by thin layers of chitosan derivatives","volume":"109","author":"Karewicz","year":"2013","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.colsurfb.2011.06.037","article-title":"Interaction of curcumin with lipid monolayers and liposomal bilayers","volume":"88","author":"Karewicz","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lachowicz, D., Mielczarek, P., Wirecka, R., Berent, K., Karewicz, A., Szuwarzy\u0144ski, M., and Zapotoczny, S. (2019). Nanohydrogels Based on Self-Assembly of Cationic Pullulan and Anionic Dextran Derivatives for Efficient Delivery of Piroxicam. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120622"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1080\/17458080.2016.1178402","article-title":"Enhanced dissolution characteristics of piroxicam-Soluplus\u00ae nanosuspensions","volume":"11","author":"Patnaik","year":"2016","journal-title":"J. Exp. Nanosci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ust\u00fcn Alkan, F., Ust\u00fcner, O., Bak\u0131rel, T., Erten, G., and Deniz, G. (2012). The Effects of Piroxicam and Deracoxib on Canine Mammary Tumour Cell Line. Sci. World J., 2012.","DOI":"10.1100\/2012\/976740"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9664\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:51Z","timestamp":1760179611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":48,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249664"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249664","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}