{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T21:12:30Z","timestamp":1775077950605,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["288 UID\/CTM\/50025\/2019"],"award-info":[{"award-number":["288 UID\/CTM\/50025\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Ministerio de Economia y Competitividad","award":["na"],"award-info":[{"award-number":["na"]}]},{"name":"V Plan Propio Universidad de Sevilla","award":["na"],"award-info":[{"award-number":["na"]}]},{"name":"European Commission (FEDER Programme)","award":["na"],"award-info":[{"award-number":["na"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>A (model) composite system for drug delivery was developed based on a thermoresponsive hydrogel loaded with microparticles. We used Pluronic F127 hydrogel as the continuous phase and alginate microparticles as the dispersed phase of this composite system. It is well known that Pluronic F127 forms a gel when added to water in an appropriate concentration and in a certain temperature range. Pluronic F127 hydrogel may be loaded with drug and injected, in its sol state, to act as a drug delivery system in physiological environment. A rheological characterization allowed the most appropriate concentration of Pluronic F127 (15.5 wt%) and appropriate alginate microparticles contents (5 and 10 wt%) to be determined. Methylene blue (MB) was used as model drug to perform drug release studies in MB loaded Pluronic hydrogel and in MB loaded alginate microparticles\/Pluronic hydrogel composite system. The latter showed a significantly slower MB release than the former (10 times), suggesting its potential in the development of dual cargo release systems either for drug delivery or tissue engineering.<\/jats:p>","DOI":"10.3390\/ma12071083","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T03:39:28Z","timestamp":1554262768000},"page":"1083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Injectable Hydrogels Based on Pluronic\/Water Systems Filled with Alginate Microparticles for Biomedical Applications"],"prefix":"10.3390","volume":"12","author":[{"given":"M. T.","family":"Cidade","sequence":"first","affiliation":[{"name":"i3N\/CENIMAT, Department of Materials Science, Faculty of Sciences and Technology, Universidade, NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"}]},{"given":"D. J.","family":"Ramos","sequence":"additional","affiliation":[{"name":"i3N\/CENIMAT, Department of Materials Science, Faculty of Sciences and Technology, Universidade, NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-1420","authenticated-orcid":false,"given":"J.","family":"Santos","sequence":"additional","affiliation":[{"name":"Applied Rheology, Colloid Technology, Chemical Engineering Department, University of Sevilla, c\/ P. Garc\u00eda Gonz\u00e1lez, 1, E41012 Sevilla, Spain"}]},{"given":"H.","family":"Carrelo","sequence":"additional","affiliation":[{"name":"i3N\/CENIMAT, Department of Materials Science, Faculty of Sciences and Technology, Universidade, NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"}]},{"given":"N.","family":"Calero","sequence":"additional","affiliation":[{"name":"Applied Rheology, Colloid Technology, Chemical Engineering Department, University of Sevilla, c\/ P. Garc\u00eda Gonz\u00e1lez, 1, E41012 Sevilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-6545","authenticated-orcid":false,"given":"J. P.","family":"Borges","sequence":"additional","affiliation":[{"name":"i3N\/CENIMAT, Department of Materials Science, Faculty of Sciences and Technology, Universidade, NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.eurpolymj.2015.05.014","article-title":"An overview of injectable polymeric hydrogels for tissue engineering","volume":"72","author":"Sivashanmugam","year":"2014","journal-title":"Eur. Polym. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/jbm.b.31000","article-title":"Neural tissue engineering of the CNS using hydrogels","volume":"87","author":"Nisbet","year":"2008","journal-title":"J. Biomater. Res. Part B: Appl. Biomater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/01.sap.0000237577.07219.b6","article-title":"Luminal fillers in nerve conduits for peripheral nerve repair","volume":"57","author":"Chen","year":"2006","journal-title":"Ann. Plast. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0074-7742(09)87010-4","article-title":"Conduit luminal additives for peripheral nerve repair","volume":"87","author":"Yan","year":"2009","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1469-7580.1999.19410001.x","article-title":"Peripheral nerve regeneration and neurotrophic factors","volume":"194","author":"Terenghi","year":"1999","journal-title":"J. Anat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/app.1991.070430207","article-title":"Kinetics of sol-to-gel transition for poloxamer polyols","volume":"43","author":"Wang","year":"1991","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11649","DOI":"10.1038\/ncomms11649","article-title":"Therapeutic surfactant-stripped frozen micelles","volume":"7","author":"Zhang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8524","DOI":"10.1002\/adma.201602373","article-title":"Surfactant-Stripped Frozen Pheophytin Micelles for Multimodal Gut Imaging","volume":"28","author":"Zhang","year":"2016","journal-title":"Adv. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.addr.2012.09.010","article-title":"Hydrogels for biomedical applications","volume":"64","author":"Hoffman","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0939-6411(00)00090-4","article-title":"Hydrogels in pharmaceutical formulations","volume":"50","author":"Peppas","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Siepmann, J., Siegel, R.A., and Rathbone, M.J. (2012). Hydrogels. Fundamentals and Applications of Controlled Release Drug Delivery, Springer. [1st ed.].","DOI":"10.1007\/978-1-4614-0881-9"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.addr.2007.03.014","article-title":"Approaches to neural tissue engineering using scaffolds for drug delivery","volume":"59","author":"Willerth","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/jbm.a.32359","article-title":"The effect of laminin peptide gradient in enzymatically cross-linked collagen scaffolds on neurite growth","volume":"92","author":"Yao","year":"2010","journal-title":"J. Biomater. Res. Part A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2174\/187152709788680698","article-title":"Polymer-based drug delivery devices for neurological disorders","volume":"8","author":"Halliday","year":"2009","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0142-9612(03)00601-X","article-title":"Striatal implantation of GDNF releasing biodegradable microspheres promotes recovery of motor function in a partial model of Parkinson\u2019s disease","volume":"25","author":"Jollivet","year":"2004","journal-title":"Biomaterials"},{"key":"ref_16","first-page":"1783","article-title":"Intravitreal injections of GDNF-loaded biodegradable microspheres are neuroprotective in a rat model of glaucoma","volume":"13","author":"Jiang","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1016\/S0142-9612(00)00141-1","article-title":"Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons","volume":"21","author":"Menei","year":"2000","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.jconrel.2004.11.004","article-title":"Carbidopa\/levodopa-loaded biodegradable microspheres: In vivo evaluation on experimental Parkinsonism in rats","volume":"102","author":"Arica","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/term.1936","article-title":"Gelatin based hydrogels as delivery systems for vascular endothelial growth factor release in peripheral nerve tissue engineering","volume":"11","author":"Gnavi","year":"2014","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_20","first-page":"197","article-title":"Development and characterisation of novel agar and gelatin injectable hydrogel as filler for peripheral nerve guidance channel","volume":"11","author":"Gnavi","year":"2014","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.3390\/ma3031746","article-title":"Injectable, Biodegradable Hydrogels for Tissue Engineering Applications","volume":"3","author":"Tan","year":"2010","journal-title":"Materials"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.seppur.2016.09.009","article-title":"Novel green micelles Pluronic F-127 coating performance on nano zero-valent iron: Enhanced reactivity and innovative kinetics","volume":"174","author":"Wang","year":"2017","journal-title":"Sep. Purif. Tech."},{"key":"ref_23","first-page":"627","article-title":"Study and description of hydrogels and organogels as vehicles for cosmetic active ingredients","volume":"60","author":"Morales","year":"2009","journal-title":"J. Cosmet. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jcis.2017.01.059","article-title":"Interface tuning and stabilization of monoglyceride mesophase dispersions: Food emulsifiers and mixtures efficiency","volume":"496","author":"Serieye","year":"2017","journal-title":"J. Coll. Interface Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.colsurfb.2014.10.022","article-title":"Development of eco-friendly submicron emulsions stabilized by a bio-derived gum","volume":"123","author":"Santos","year":"2014","journal-title":"Colloids Surf. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijpharm.2017.01.058","article-title":"Relating emulsion stability to interfacial properties for pharmaceutical emulsions stabilized by Pluronic F68 surfactant","volume":"521","author":"Powell","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.colsurfa.2011.04.019","article-title":"Dynamic interfacial tension of triblock copolymers solutions at the water-hexane interface","volume":"391","author":"Fainerman","year":"2011","journal-title":"Colloids Surf. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8452","DOI":"10.1021\/jp982568o","article-title":"Micellar structure of an ethylene oxide\u2212propylene oxide block copolymer: A small-angle neutron scattering study","volume":"102","author":"Jain","year":"1998","journal-title":"J. Phys. Chem. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00396-015-3757-7","article-title":"The influence of poly (acrylic acid) on micellization and gelation characteristics of aqueous Pluronic F127 copolymer system","volume":"294","author":"Pragatheeswaran","year":"2016","journal-title":"Colloid Polym. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Senior, J., and Radomsky, M.L. (2000). Dunn, In situ gelling systems. Sustained-Release Injectable Products, CRC Press. [1st ed.].","DOI":"10.1201\/b14421"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0197-4580(89)90156-5","article-title":"Site-specific drug delivery to CNS: Old and new","volume":"10","author":"Hollister","year":"1989","journal-title":"Neurobiol. Aging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0927-7757(94)03028-X","article-title":"Poly (ethylene oxide)- poly (propylene oxide)- poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: Thermodynamics, structure, dynamics, and modeling","volume":"96","author":"Alexandridis","year":"1995","journal-title":"Colloids Surf. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1021\/ma00093a016","article-title":"Phase diagrams and aggregation behavior of poly (oxyethylene)-poly (oxypropylene)-poly (oxyethylene) triblock copolymers in aqueous solutions","volume":"27","author":"Wanka","year":"1994","journal-title":"Macromolecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1002\/polb.20105","article-title":"Micellization to gelation of a triblock copolymer in water: Thermoreversibility and scaling","volume":"42","author":"Lau","year":"2004","journal-title":"J. Polym. Sci. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ijpharm.2004.03.029","article-title":"Effect of anti-inflammatories on Pluronic F127: Micellar assembly, gelation and partitioning","volume":"278","author":"Sharma","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1039\/C7SM02540H","article-title":"Drop spreading and gelation of thermoresponsive polymers","volume":"14","author":"Royon","year":"2018","journal-title":"Soft Matter"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1007\/s00396-018-4370-3","article-title":"Time-dependent behavior in analyte-, temperature-, and shear-sensitive Pluronic PE9400\/water systems","volume":"296","author":"Calero","year":"2018","journal-title":"Colloid Polym. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1122\/1.5054598","article-title":"Gelation and long-time relaxation of aqueous solutions of Pluronic F127","volume":"63","author":"Hopkins","year":"2019","journal-title":"J. Rheol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.colsurfa.2007.05.006","article-title":"Preparation of temperature-sensitive microemulsion-based gels formed from a triblock copolymer","volume":"307","author":"Zhao","year":"2007","journal-title":"Colloids Surf. A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1021\/bm0496965","article-title":"In situ gelling of alginate\/pluronic solutions for ophthalmic delivery of pilocarpine","volume":"5","author":"Lin","year":"2004","journal-title":"Biomacromolecules"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpharm.2015.04.048","article-title":"Pluronic-based functional polymeric mixed micelles for co-delivery of doxorubicin and paclitaxel to multidrug resistant tumor","volume":"488","author":"Chen","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1016\/j.biomaterials.2009.01.006","article-title":"Dual-drug delivery system based on hydrogel\/micelle composites","volume":"30","author":"Wei","year":"2009","journal-title":"Biomaterials"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.carbpol.2015.10.019","article-title":"A novel composite matrix based on polymeric micelle and hydrogel as a drug carrier for the controlled release of dual drugs","volume":"136","author":"Anirudhan","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.colsurfb.2017.02.008","article-title":"Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties","volume":"153","author":"Murata","year":"2017","journal-title":"Colloids Surf. B"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.actbio.2015.03.013","article-title":"Core\u2013shell designed scaffolds for drug delivery and tissue engineering","volume":"21","author":"Perez","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jconrel.2015.08.049","article-title":"Controlled drug release for tissue engineering","volume":"219","author":"Rambhia","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1208\/s12248-010-9185-1","article-title":"DDSolver: An add-in program for modeling and comparison of drug dissolution profiles","volume":"12","author":"Zhang","year":"2010","journal-title":"AAPS J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.carbpol.2016.07.109","article-title":"Towards the development of multifunctional chitosan-based iron oxide nanoparticles: Optimization and modelling of doxorubicin release","volume":"153","author":"Soares","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.carbpol.2016.03.028","article-title":"Chitosan-based nanoparticles as drug delivery systems for doxorubicin: Optimization and modelling","volume":"147","author":"Soares","year":"2016","journal-title":"Carbohydr. Polym."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/12\/7\/1083\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:42:17Z","timestamp":1760186537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/12\/7\/1083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,2]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["ma12071083"],"URL":"https:\/\/doi.org\/10.3390\/ma12071083","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,2]]}}}