{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T03:59:36Z","timestamp":1776830376574,"version":"3.51.2"},"reference-count":72,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2020.06766.BD"],"award-info":[{"award-number":["2020.06766.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["2020.06766.BD"],"award-info":[{"award-number":["2020.06766.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle\u2013hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 \u00b0C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol\u2013gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe\u2013needle systems with acceptable force (2.2\u201313.4 N) and work (49.5\u2013317.7 N\u00b7mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 \u00b0C and underwent rapid gelation at 37 \u00b0C. However, their sterilized counterparts gelled at 1\u20132 \u00b0C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.<\/jats:p>","DOI":"10.3390\/gels10050307","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T03:30:49Z","timestamp":1714534249000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Rheological and Injectability Evaluation of Sterilized Poloxamer-407-Based Hydrogels Containing Docetaxel-Loaded Lipid Nanoparticles"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1247-6738","authenticated-orcid":false,"given":"Ana Camila","family":"Marques","sequence":"first","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-3398","authenticated-orcid":false,"given":"Paulo C.","family":"Costa","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-8234","authenticated-orcid":false,"given":"S\u00e9rgia","family":"Velho","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-3366","authenticated-orcid":false,"given":"Maria Helena","family":"Amaral","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Carvalho, F.V., Ribeiro, L.N.M., Moura, L.D., Rodrigues da Silva, G.H., Mitsutake, H., Mendon\u00e7a, T.C., Geronimo, G., Breitkreitz, M.C., and de Paula, E. (2022). Docetaxel Loaded in Copaiba Oil-Nanostructured Lipid Carriers as a Promising DDS for Breast Cancer Treatment. Molecules, 27.","DOI":"10.3390\/molecules27248838"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1136779","DOI":"10.3389\/fphar.2023.1136779","article-title":"Biosynthesis of anticancer phytochemical compounds and their chemistry","volume":"14","author":"Dogra","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Razak, S.A., Mohd Gazzali, A., Fisol, F.A.M., Abdulbaqi, I., Parumasivam, T., Mohtar, N.A., and Wahab, H. (2021). Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: An Overview. Cancers, 13.","DOI":"10.3390\/cancers13030400"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"964076","DOI":"10.3389\/fphar.2022.964076","article-title":"A novel form of docetaxel polymeric micelles demonstrates anti-tumor and ascites-inhibitory activities in animal models as monotherapy or in combination with anti-angiogenic agents","volume":"13","author":"Guo","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jurczyk, M., Kasperczyk, J., Wrze\u015bniok, D., Beberok, A., and Jelonek, K. (2022). Nanoparticles Loaded with Docetaxel and Resveratrol as an Advanced Tool for Cancer Therapy. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051187"},{"key":"ref_6","first-page":"e29059","article-title":"The Application of Nanotechnology and Nanomaterials in Cancer Diagnosis and Treatment: A Review","volume":"14","author":"Kher","year":"2022","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Marques, A.C., Costa, P.C., Velho, S., and Amaral, M.H. (2023). Lipid Nanoparticles Functionalized with Antibodies for Anticancer Drug Therapy. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010216"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16014","DOI":"10.1038\/natrevmats.2016.14","article-title":"Analysis of nanoparticle delivery to tumours","volume":"1","author":"Wilhelm","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1021\/acsnano.9b08142","article-title":"Meta-Analysis of Nanoparticle Delivery to Tumors Using a Physiologically Based Pharmacokinetic Modeling and Simulation Approach","volume":"14","author":"Cheng","year":"2020","journal-title":"ACS Nano"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"114708","DOI":"10.1016\/j.addr.2023.114708","article-title":"Nanoparticle biodistribution coefficients: A quantitative approach for understanding the tissue distribution of nanoparticles","volume":"194","author":"Kumar","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yun, W.S., Kim, J., Lim, D.K., Kim, D.H., Jeon, S.I., and Kim, K. (2023). Recent Studies and Progress in the Intratumoral Administration of Nano-Sized Drug Delivery Systems. Nanomaterials, 13.","DOI":"10.3390\/nano13152225"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7409","DOI":"10.2147\/IJN.S178585","article-title":"Peritumoral implantation of hydrogel-containing nanoparticles and losartan for enhanced nanoparticle penetration and antitumor effect","volume":"13","author":"Shen","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"23838","DOI":"10.1039\/D0NR05053A","article-title":"Intratumoral injection of hydrogel-embedded nanoparticles enhances retention in glioblastoma","volume":"12","author":"Brachi","year":"2020","journal-title":"Nanoscale"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7435","DOI":"10.1039\/D3TB00187C","article-title":"Development of cationic peptide-based hydrogels loaded with iopamidol for CEST-MRI detection","volume":"11","author":"Rosa","year":"2023","journal-title":"J. Mater. Chem. B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1039\/D3BM01840G","article-title":"Injectable hydrogels as emerging drug-delivery platforms for tumor therapy","volume":"12","author":"Cheng","year":"2024","journal-title":"Biomater. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41565-020-00843-7","article-title":"Immunostimulant hydrogel for the inhibition of malignant glioma relapse post-resection","volume":"16","author":"Zhang","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, X., Guo, X., Wu, Y., and Gao, J. (2021). Locally Injectable Hydrogels for Tumor Immunotherapy. Gels, 7.","DOI":"10.3390\/gels7040224"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.actbio.2023.01.015","article-title":"A guide to preclinical evaluation of hydrogel-based devices for treatment of cartilage lesions","volume":"158","author":"Karami","year":"2023","journal-title":"Acta Biomater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/j.drudis.2021.04.012","article-title":"Stimuli-responsive hydrogels for intratumoral drug delivery","volume":"26","author":"Marques","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jconrel.2017.08.006","article-title":"Injectable hydrogels for sustained release of therapeutic agents","volume":"267","author":"Thambi","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tanga, S., Aucamp, M., and Ramburrun, P. (2023). Injectable Thermoresponsive Hydrogels for Cancer Therapy: Challenges and Prospects. Gels, 9.","DOI":"10.3390\/gels9050418"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fan, R., Cheng, Y., Wang, R., Zhang, T., Zhang, H., Li, J., Song, S., and Zheng, A. (2022). Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy. Polymers, 14.","DOI":"10.3390\/polym14122379"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, I.C., Su, C.Y., Chen, P.Y., Hoang, T.C., Tsou, Y.S., and Fang, H.W. (2022). Investigation and Characterization of Factors Affecting Rheological Properties of Poloxamer-Based Thermo-Sensitive Hydrogel. Polymers, 14.","DOI":"10.3390\/polym14245353"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, Y., Lee, J.H., Meng, M., Cui, N., Dai, C.Y., Jia, Q., Lee, E.S., and Jiang, H.B. (2021). An Overview on Thermosensitive Oral Gel Based on Poloxamer 407. Materials, 14.","DOI":"10.3390\/ma14164522"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Giuliano, E., Paolino, D., Fresta, M., and Cosco, D. (2018). Drug-Loaded Biocompatible Nanocarriers Embedded in Poloxamer 407 Hydrogels as Therapeutic Formulations. Medicines, 6.","DOI":"10.3390\/medicines6010007"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Giuliano, E., Paolino, D., Fresta, M., and Cosco, D. (2018). Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030159"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.canlet.2018.11.011","article-title":"Intratumoral injection of gels containing losartan microspheres and (PLG-g-mPEG)-cisplatin nanoparticles improves drug penetration, retention and anti-tumor activity","volume":"442","author":"Yu","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jconrel.2013.10.026","article-title":"Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity","volume":"174","author":"Lin","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.colsurfb.2015.12.057","article-title":"Evaluation of TPGS-modified thermo-sensitive Pluronic PF127 hydrogel as a potential carrier to reverse the resistance of P-gp-overexpressing SMMC-7721 cell lines","volume":"140","author":"Gao","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.2217\/nnm.14.211","article-title":"Novel injectable thermosensitive hydrogels for delivering hyaluronic acid-doxorubicin nanocomplexes to locally treat tumors","volume":"10","author":"Jhan","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ejpb.2012.12.019","article-title":"Administration of the optimized \u03b2-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model","volume":"84","author":"Seoane","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1002\/jbm.b.34048","article-title":"Sterilization of hydrogels for biomedical applications: A review","volume":"106","author":"Galante","year":"2018","journal-title":"J. Biomed. Mater. Res. Part B"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"122671","DOI":"10.1016\/j.ijpharm.2023.122671","article-title":"A review of conventional and emerging technologies for hydrogels sterilization","volume":"634","author":"Bento","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jddst.2016.04.010","article-title":"Development of mucoadhesive and thermosensitive eyedrops to improve the ophthalmic bioavailability of ibuprofen","volume":"35","author":"Almeida","year":"2016","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zheng, Q., Su, H., Huang, Z., and Wang, G. (2023). Synthesis and Characteristics of a pH-Sensitive Sol-Gel Transition Colloid for Coal Fire Extinguishing. Gels, 9.","DOI":"10.3390\/gels9010069"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/eye.2017.267","article-title":"What is rheology?","volume":"32","author":"Wilson","year":"2018","journal-title":"Eye"},{"key":"ref_37","first-page":"52081","article-title":"Thermogelation Analysis Of F127-Water Mixtures By Physical Chemistry Techniques","volume":"20","author":"Gentile","year":"2019","journal-title":"Appl. Rheol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/marc.201400586","article-title":"Chitosan-PEG hydrogel with sol-gel transition triggerable by multiple external stimuli. Macromol","volume":"36","author":"Tsao","year":"2015","journal-title":"Rapid Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16668","DOI":"10.1039\/C7RA00552K","article-title":"Nanostructured lipid carrier (NLC)-based novel hydrogels as potential carriers for nepafenac applied after cataract surgery for the treatment of inflammation: Design, characterization and in vitro cellular inhibition and uptake studies","volume":"7","author":"Yu","year":"2017","journal-title":"RSC Adv."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Calixto, G.M.F., Muniz, B.V., Castro, S.R., de Araujo, J.S.M., de Souza Amorim, K., Ribeiro, L.N.M., Ferreira, L.E.N., de Ara\u00fajo, D.R., de Paula, E., and Franz-Montan, M. (2021). Mucoadhesive, Thermoreversible Hydrogel, Containing Tetracaine-Loaded Nanostructured Lipid Carriers for Topical, Intranasal Needle-Free Anesthesia. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111760"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/jbm.b.34703","article-title":"Autoclaving of Poloxamer 407 hydrogel and its use as a drug delivery vehicle","volume":"109","author":"Beard","year":"2021","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ferreira, I., Marques, A.C., Costa, P.C., and Amaral, M.H. (2023). Effects of Steam Sterilization on the Properties of Stimuli-Responsive Polymer-Based Hydrogels. Gels, 9.","DOI":"10.3390\/gels9050385"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13027","DOI":"10.1007\/s10853-022-07468-2","article-title":"Injectability study and rheological evaluation of Pluronic-derived thermosensitive hydrogels containing mesoporous bioactive glass nanoparticles for bone regeneration","volume":"57","author":"Queiroz","year":"2022","journal-title":"J. Mater. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16071","DOI":"10.1038\/natrevmats.2016.71","article-title":"Designing hydrogels for controlled drug delivery","volume":"1","author":"Li","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"eaaz0868","DOI":"10.1126\/science.aaz0868","article-title":"Physical traits of cancer","volume":"370","author":"Nia","year":"2020","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1021\/acs.langmuir.1c01587","article-title":"Cubic and Hexagonal Mesophases for Protein Encapsulation: Structural Effects of Insulin Confinement","volume":"37","author":"Astolfi","year":"2021","journal-title":"Langmuir"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20530","DOI":"10.1021\/acsami.5b06043","article-title":"Preparation of a Thermosensitive Gel Composed of a mPEG-PLGA-PLL-cRGD Nanodrug Delivery System for Pancreatic Tumor Therapy","volume":"7","author":"Shen","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Marques, A.C., Costa, P.C., Velho, S., and Amaral, M.H. (2023). Injectable Poloxamer Hydrogels for Local Cancer Therapy. Gels, 9.","DOI":"10.3390\/gels9070593"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Abdeltawab, H., Svirskis, D., Hill, A.G., and Sharma, M. (2022). Increasing the Hydrophobic Component of Poloxamers and the Inclusion of Salt Extend the Release of Bupivacaine from Injectable In Situ Gels, While Common Polymer Additives Have Little Effect. Gels, 8.","DOI":"10.3390\/gels8080484"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1208\/s12249-018-0963-x","article-title":"Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated Biopharmaceuticals: Assessment of Injectability via Measurement of Total Work Done \u201cW(T)\u201d","volume":"19","author":"Zhang","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Casiraghi, A., Gennari, C.G., Musazzi, U.M., Ortenzi, M.A., Bordignon, S., and Minghetti, P. (2020). Mucoadhesive Budesonide Formulation for the Treatment of Eosinophilic Esophagitis. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030211"},{"key":"ref_52","first-page":"Cd010720","article-title":"Needle size for vaccination procedures in children and adolescents","volume":"8","author":"Beirne","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ry\u0142, A., and Owczarz, P. (2021). Influence of Injection Application on the Sol-Gel Phase Transition Conditions of Polysaccharide-Based Hydrogels. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413208"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1021\/acsbiomaterials.7b00734","article-title":"Methods To Assess Shear-Thinning Hydrogels for Application As Injectable Biomaterials","volume":"3","author":"Chen","year":"2017","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gou, S., Porcello, A., All\u00e9mann, E., Salomon, D., Micheels, P., Jordan, O., and Kalia, Y.N. (2023). Injectable Hyaluronan-Based Thermoresponsive Hydrogels for Dermatological Applications. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061708"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ejps.2008.12.003","article-title":"Injectability of biodegradable in situ forming microparticle systems (ISM)","volume":"36","author":"Rungseevijitprapa","year":"2009","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ry\u0142, A., and Owczarz, P. (2020). Injectability of Thermosensitive, Low-Concentrated Chitosan Colloids as Flow Phenomenon through the Capillary under High Shear Rate Conditions. Polymers, 12.","DOI":"10.3390\/polym12102260"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s10973-017-6139-1","article-title":"Pluronic F127 as a suitable carrier for preparing the imatinib base solid dispersions and its potential in development of a modified release dosage forms","volume":"130","author":"Karolewicz","year":"2017","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ali, A., Madni, A., Shah, H., Jamshaid, T., Jan, N., Khan, S., Khan, M.M., and Mahmood, M.A. (2023). Solid lipid-based nanoparticulate system for sustained release and enhanced in-vitro cytotoxic effect of 5-fluorouracil on skin Melanoma and squamous cell carcinoma. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0281004"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"751321","DOI":"10.3389\/fphar.2021.751321","article-title":"Encapsulated Escitalopram and Paroxetine Intranasal Co-Administration: In Vitro\/In Vivo Evaluation","volume":"12","author":"Silva","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejpb.2020.04.011","article-title":"QbD-driven development of intranasal lipid nanoparticles for depression treatment","volume":"153","author":"Vitorino","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ajps.2018.08.001","article-title":"Extended tacrolimus release via the combination of lipid-based solid dispersion and HPMC hydrogel matrix tablets","volume":"14","author":"Xu","year":"2019","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., Rubio-P\u00e9rez, G., Bach, A., Mu\u00f1oz-Rujas, N., Aguilar, F., and Worlitschek, J. (2020). Consistent DSC and TGA Methodology as Basis for the Measurement and Comparison of Thermo-Physical Properties of Phase Change Materials. Materials, 13.","DOI":"10.3390\/ma13204486"},{"key":"ref_64","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_65","first-page":"471","article-title":"Impact of sterilisation conditions on the rheological properties of thermoresponsive pluronic F-127-based gels for the ophthalmic use","volume":"75","author":"Burak","year":"2018","journal-title":"Acta Pol. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Stojkov, G., Niyazov, Z., Picchioni, F., and Bose, R.K. (2021). Relationship between Structure and Rheology of Hydrogels for Various Applications. Gels, 7.","DOI":"10.3390\/gels7040255"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Panyamao, P., Ruksiriwanich, W., Sirisa-Ard, P., and Charumanee, S. (2020). Injectable Thermosensitive Chitosan\/Pullulan-Based Hydrogels with Improved Mechanical Properties and Swelling Capacity. Polymers, 12.","DOI":"10.3390\/polym12112514"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1208\/s12249-011-9625-y","article-title":"Injectability evaluation: An open issue","volume":"12","author":"Cilurzo","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"122486","DOI":"10.1016\/j.ijpharm.2022.122486","article-title":"Understanding syringeability and injectability of high molecular weight PEO solution through time-dependent force-distance profiles","volume":"631","author":"Feng","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pires, T., Oliveira, A.S., Marques, A.C., Salema-Oom, M., Figueiredo-Pina, C.G., Silva, D., and Serro, A.P. (2022). Effects of Non-Conventional Sterilisation Methods on PBO-Reinforced PVA Hydrogels for Cartilage Replacement. Gels, 8.","DOI":"10.3390\/gels8100640"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/jbm.a.36794","article-title":"Sterilized chitosan-based composite hydrogels: Physicochemical characterization and in vitro cytotoxicity","volume":"108","author":"Knauth","year":"2020","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Oliveira, A.S., Silva, J.C., Loureiro, M.V., Marques, A.C., Kotov, N.A., Cola\u00e7o, R., and Serro, A.P. (2023). Super-Strong Hydrogel Composites Reinforced with PBO Nanofibers for Cartilage Replacement. Macromol. Biosci., 23.","DOI":"10.1002\/mabi.202200240"}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/10\/5\/307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:37:56Z","timestamp":1760107076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/10\/5\/307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,1]]},"references-count":72,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["gels10050307"],"URL":"https:\/\/doi.org\/10.3390\/gels10050307","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,1]]}}}