{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T21:10:28Z","timestamp":1766178628376,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"Ministry of Research, Innovation and Digitization, CNCS\/CCCDI\u2014UEFISCDI","doi-asserted-by":"publisher","award":["PN-III-P4-ID-PCE-2020-1541"],"award-info":[{"award-number":["PN-III-P4-ID-PCE-2020-1541"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Crosslinked porous microparticles have received great attention as drug delivery systems lately due to their unique set of properties: the capability to form various polymer\u2013drug combinations, low immunogenicity, patient compliance and ability to release drugs in a delayed or controlled manner. Moreover, polymers with betaine groups have shown some unique features such as antifouling, antimicrobial activity, biocompatibility and strong hydration properties. Herein, novel porous zwitterionic microparticles were prepared in two stages. The first step involves the synthesis of porous microparticles based on glycidyl methacrylate, N-vinylimidazole and triethyleneglycol dimethacrylate using the suspension polymerization technique, the second step being the synthesis of zwitterionic porous microparticles by polymer\u2013analogous reaction in presence of sodium monochloroacetate as betainization agent. Both types of microparticles were characterized structurally and morphologically by FT-IR spectroscopy, energy dispersive X-ray analysis, scanning electron microscopy, dynamic vapors sorption and mercury porosimetry. The tetracycline loading into crosslinked and zwitterionic microparticles was also performed, the maximum tetracycline loading capacities being 87 mg\/g and 135 mg\/g, respectively. The drug release mechanism, elucidated by various mathematical models, is controlled by both diffusion and swelling processes as a function of the zwitterionic and\/or porous microparticle structure. Both types of microparticles presented antibacterial activity against the two reference strains used in this study: Escherichia coli and Staphylococcus aureus.<\/jats:p>","DOI":"10.3390\/ijms232314999","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T02:21:57Z","timestamp":1669774917000},"page":"14999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Porous Crosslinked Zwitterionic Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole as Possible Drug Delivery Systems"],"prefix":"10.3390","volume":"23","author":[{"given":"Marin-Aurel","family":"Trofin","sequence":"first","affiliation":[{"name":"\u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41A, 700487 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9653-707X","authenticated-orcid":false,"given":"Stefania","family":"Racovita","sequence":"additional","affiliation":[{"name":"\u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41A, 700487 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8092-6967","authenticated-orcid":false,"given":"Silvia","family":"Vasiliu","sequence":"additional","affiliation":[{"name":"\u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41A, 700487 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0042-671X","authenticated-orcid":false,"given":"Ana-Lavinia","family":"Vasiliu","sequence":"additional","affiliation":[{"name":"\u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41A, 700487 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3193-0609","authenticated-orcid":false,"given":"Marcela","family":"Mihai","sequence":"additional","affiliation":[{"name":"\u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41A, 700487 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3797\/scipharm.1307-03","article-title":"Preparation in vitro characterization and in vivo pharmacokinetic evaluation of respirable porous microparticles containing rifampicin","volume":"82","author":"Kundawala","year":"2014","journal-title":"Sci. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1021\/acs.chemrev.6b00439","article-title":"Porous organic materials: Strategic design and structure-function-correlation","volume":"117","author":"Das","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.progpolymsci.2011.07.006","article-title":"Porous polymer particles-A comprehensive guide to synthesis, characterization, functionalization and applications","volume":"37","year":"2012","journal-title":"Prog. Polym. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ijpharm.2018.06.015","article-title":"Porous microspheres: Synthesis, characterization and applications in pharmaceutical & medical fields","volume":"548","author":"Saha","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"799","DOI":"10.3389\/fbioe.2020.00799","article-title":"Porous polymeric microspheres with controllable pore diameters for tissue engineering lung tumor model development","volume":"8","author":"Dhamecha","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1007\/s00289-015-1459-4","article-title":"Synthesis, characterization and adsorption properties of alginate-porous beads","volume":"72","author":"Peretz","year":"2015","journal-title":"Polym. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.carbpol.2005.12.009","article-title":"Preparation and characterization of crosslinked porous cellulose beads","volume":"64","author":"Bai","year":"2006","journal-title":"Carbohydr. Polym."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/15685551.2018.1489698","article-title":"A novel route for synthesis of crosslinked polystyrene copolymer beads with tunable porosity using guar and xanthan gums from bioresources as alternative synthetic suspension stabilizers","volume":"21","author":"Rahmatpour","year":"2018","journal-title":"Des. Monom. Polym."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12781","DOI":"10.1021\/acs.langmuir.1c01508","article-title":"Cross-linked porous gelatin microparticles with tunable shape, size and porosity","volume":"37","author":"Gelli","year":"2021","journal-title":"Langmuir"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.arabjc.2018.04.004","article-title":"Microparticles based on carboxymethyl starch\/chitosan polyelectrolyte complex as vehicles for drug delivery systems","volume":"13","author":"Quadrado","year":"2020","journal-title":"Arabian J. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0927-7757(00)00777-9","article-title":"Production of porous suspension polymer beads with a narrow size distribution using a cross-flow membrane and a continuous tubular reactor","volume":"180","author":"Dowding","year":"2001","journal-title":"Colloids Surf. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1002\/app.24604","article-title":"Suspension copolymerization of styrene and divinylbenzene: Formation of beads","volume":"101","author":"Gupta","year":"2006","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/02652048.2017.1324919","article-title":"Core-shell PLA-PVA porous microparticles as carriers for bacteriocin nisin","volume":"34","author":"Holcapkova","year":"2017","journal-title":"J. Microencapsul."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"026103","DOI":"10.1063\/1.5008556","article-title":"Porous microspheres support mesemchymal progenitor cell ingrowth and stimulate angiogenesis","volume":"2","author":"Peterson","year":"2018","journal-title":"APL Bioeng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1039\/c3tb20192a","article-title":"Composite cyclodextrin-calcium carbonate porous microparticles and modified multilayer capsules: Novel carriers for encapsulation of hydrophobic drugs","volume":"1","author":"Kurapati","year":"2013","journal-title":"J. Mater. Chem. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1021\/acsapm.9b00897","article-title":"Polyzwitterions: From surface properties and bioactivity profiles to biomedical applications","volume":"2","author":"Paschke","year":"2020","journal-title":"ACS Appl. Polym. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.actbio.2016.04.011","article-title":"Zwitterionic mesoporous nanoparticles with a bioresponsive gatekeeper for cancer therapy","volume":"40","author":"Khatoon","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/j.csbj.2020.07.015","article-title":"Novel zwitterionic vectors: Multifunctional delivery system for therapeutic genes and drugs","volume":"18","author":"Zhou","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.actbio.2016.03.046","article-title":"Zwitterionic surface grafting of epoxylated sulfobetaine copolymers for development of stealth biomaterials interfaces","volume":"40","author":"Chou","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8928","DOI":"10.1016\/j.biomaterials.2012.09.011","article-title":"Synchronizing nonfouling and antimicrobial properties in a zwitterionic hydrogels","volume":"33","author":"Mi","year":"2012","journal-title":"Biomaterials"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.chroma.2019.06.026","article-title":"Evaluation of superficially porous particle based zwitterionic chiral ion exchangers against fully porous particles benchmarks for enantioselective ultra-high performance liquid chromatography","volume":"1603","author":"Geibel","year":"2019","journal-title":"J. Chromat. A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"58223","DOI":"10.1021\/acsami.0c17427","article-title":"Stimuli-responsive zwitterionic core-shell microgels for antifouling surface coatings","volume":"12","author":"Saha","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.jcis.2004.08.157","article-title":"Resistance of zwitterionic telomers accumulated on metal surfaces against nonspecific adsorption of proteins","volume":"282","author":"Kitano","year":"2005","journal-title":"J. Colloid. Interface Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s00289-015-1586-y","article-title":"Synthesis and characterization of monodisperse-porous zwitterionic microbeads","volume":"73","author":"Kibar","year":"2016","journal-title":"Polym. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22018","DOI":"10.1021\/acsami.6b06343","article-title":"Synthesis of zwitterionic polymer particles via combined distillation precipitation polymerization and click chemistry for high efficient enrichment of glycopeptide","volume":"8","author":"Liu","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.cej.2010.07.002","article-title":"Adsorption studies of some inorganic and organic salts on new zwitterionic ion exchangers with carboxybetaine moieties","volume":"162","author":"Neagu","year":"2010","journal-title":"Chem. Eng. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104997","DOI":"10.1016\/j.reactfunctpolym.2021.104997","article-title":"Design of multifunctional composite materials based on acrylic ion exchangers and CaCO3 as sorbents for small organic molecules","volume":"166","author":"Zaharia","year":"2021","journal-title":"React. Funct. Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"135383","DOI":"10.1016\/j.chemosphere.2022.135383","article-title":"Stable and reusable acrylic ion-exchangers. From HMIs highly polluted tailing pond to safe and clean water","volume":"304","author":"Zaharia","year":"2022","journal-title":"Chemosphere"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125225","DOI":"10.1016\/j.matchemphys.2021.125225","article-title":"Multifunctional composites of zwitterionic resins and silver nanoparticles for point-of-demand antimicrobial applications","volume":"275","author":"Zaharia","year":"2022","journal-title":"Mater. Chem. Phys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2016015798","article-title":"Overview on therapeutic applications of microparticulate drug delivery systems","volume":"33","author":"Bale","year":"2016","journal-title":"Crit. Rev. Therapeut. Drug Carr. Syst."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lengyel, M., Kallai-Szabo, N., Antal, V., Laki, A.J., and Antal, I. (2019). Micropaticles, microspheres and microxapsules for advanced drug delivery. Sci. Pharm., 87.","DOI":"10.3390\/scipharm87030020"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Racovita, S., Trofin, M.-A., Loghin, D.F., Zaharia, M.-M., Bucatariu, F., Mihai, M., and Vasiliu, S. (2021). Polybetaines in biomedical applications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179321"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"55874","DOI":"10.1039\/C7RA11093F","article-title":"Post-polymerization modification reactions of poly(glycidyl methacrylate)s","volume":"7","author":"Muzammil","year":"2017","journal-title":"RSC Adv."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cardil, A., Palenzuela, M., Vega, J.F., and Mosquera, M.E.G. (2022). Rheology of poly(glycidyl methacrylate) macromolecular nanoassemblies. Polymers, 14.","DOI":"10.3390\/polym14030455"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.carbpol.2006.10.008","article-title":"Synthesis, characterization and antibacterial activity of poly(N-vinylimidazole) grafted chitosan","volume":"69","author":"Caner","year":"2007","journal-title":"Carbohydr. Polym."},{"key":"ref_36","first-page":"333","article-title":"Solution properties of three polyzwitterions based on poly(N-vinylimidazole)","volume":"19","author":"Racovita","year":"2010","journal-title":"Iran Polym. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cemconres.2013.11.008","article-title":"A study of the water vapor sorption isotherms of hardebed cement pastes: Possible pore structure changes at low relative humidity and the impact of temperature on isotherms","volume":"56","author":"Wu","year":"2014","journal-title":"Cem. Concr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.micromeso.2018.06.026","article-title":"Insights into the S-shaped sorption isotherms and their dimensionless forms","volume":"272","author":"Inglezakis","year":"2018","journal-title":"Microporous Mesoporous Mater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.eng.2018.06.001","article-title":"Progress in the physisorption characterization of nanoporous gas storage materials","volume":"4","author":"Cychosz","year":"2018","journal-title":"Engineering"},{"key":"ref_40","first-page":"395","article-title":"Spectroscopic characterization of chloramphenicol and tetracycline: An impact of biofield treatment","volume":"6","author":"Trivedi","year":"2015","journal-title":"Pharmaceut. Anal. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2165\/00137696-200402010-00003","article-title":"Factors affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery system","volume":"2","author":"Varma","year":"2004","journal-title":"Am. J. Drug Deliv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/jps.2600560302","article-title":"Diffusional models useful in biopharmaceutics. Drug release rate processes","volume":"56","author":"Higuchi","year":"1967","journal-title":"J. Pharm. Sci."},{"key":"ref_43","first-page":"217","article-title":"Kinetic modeling on drug release from controlled drug delivery systems","volume":"67","author":"Dash","year":"2010","journal-title":"Acta Pol. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0378-5173(83)90064-9","article-title":"Mechanisms of solute release from porous hydrophilic polymers","volume":"15","author":"Korsmeyer","year":"1983","journal-title":"Int. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"16167","DOI":"10.1039\/C9RA01068H","article-title":"Preparation and in vitro release kinetics of nitrendipine-loaded PLLA-PEG-PLLA microparticles by supercritical solution impregnation process","volume":"9","author":"Zhan","year":"2019","journal-title":"RSC Adv."},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1177\/2211068211428189","article-title":"Reservoir-based polymer drug delivery systems","volume":"17","author":"Yang","year":"2012","journal-title":"J. Lab. Autom."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"430","DOI":"10.4028\/www.scientific.net\/MSF.729.430","article-title":"Evaluation methods of antimicrobial activity of plastics","volume":"729","author":"Kun","year":"2013","journal-title":"Mater. Sci. Forum"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.micromeso.2005.06.015","article-title":"Storage and release of ibuprofen drug molecules in hollow mesoporous silica spheres with modified pore surface","volume":"85","author":"Zhu","year":"2005","journal-title":"Microporous Mesoporous Mater."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14999\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:01Z","timestamp":1760146201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,30]]},"references-count":49,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314999"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314999","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,11,30]]}}}