{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:22:07Z","timestamp":1775445727485,"version":"3.50.1"},"reference-count":163,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"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":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","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":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","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":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","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":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","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>Proteins and peptides are potential therapeutic agents, but their physiochemical properties make their use as drug substances challenging. Hydrogels are hydrophilic polymeric networks that can swell and retain high amounts of water or biological fluids without being dissolved. Due to their biocompatibility, their porous structure, which enables the transport of various peptides and proteins, and their protective effect against degradation, hydrogels have gained prominence as ideal carriers for these molecules\u2019 delivery. Particularly, stimuli-responsive hydrogels exhibit physicochemical transitions in response to subtle modifications in the surrounding environment, leading to the controlled release of entrapped proteins or peptides. This review is focused on the application of these hydrogels in protein and peptide delivery, including a brief overview of therapeutic proteins and types of stimuli-responsive polymers.<\/jats:p>","DOI":"10.3390\/gels9100802","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:49:29Z","timestamp":1696578569000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Stimuli-Responsive Hydrogels for Protein Delivery"],"prefix":"10.3390","volume":"9","author":[{"given":"Rafaela","family":"Malta","sequence":"first","affiliation":[{"name":"CeNTI\u2014Centre for Nanotechnology and Smart Materials, Rua Fernando Mesquita, 2785, 4760-034 Vila Nova de Famalic\u00e3o, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1247-6738","authenticated-orcid":false,"given":"Ana Camila","family":"Marques","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-3398","authenticated-orcid":false,"given":"Paulo Cardoso da","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, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 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, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.csbj.2019.09.004","article-title":"Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery","volume":"17","author":"Bajracharya","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/nbt.4305","article-title":"Biopharmaceutical benchmarks 2018","volume":"36","author":"Walsh","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13346-020-00746-z","article-title":"Advanced trends in protein and peptide drug delivery: A special emphasis on aquasomes and microneedles techniques","volume":"11","author":"Asfour","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_4","unstructured":"Florence, A.T., and Attwood, D. (2015). Physicochemical Principles of Pharmacy: In Manufacture, Formulation and Clinical Use, Pharmaceutical Press. [6th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"661","DOI":"10.2174\/138920009789895499","article-title":"Pharmacokinetics of biotech drugs: Peptides, proteins and monoclonal antibodies","volume":"10","author":"Lin","year":"2009","journal-title":"Curr. Drug Metab."},{"key":"ref_6","first-page":"166","article-title":"Non-invasive strategies for protein drug delivery: Oral, transdermal, and pulmonary","volume":"10","author":"Irianti","year":"2020","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1021\/cr200157d","article-title":"Hydrogels for protein delivery","volume":"112","author":"Vermonden","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1039\/C6BM00330C","article-title":"Emerging hydrogel designs for controlled protein delivery","volume":"4","author":"Bae","year":"2016","journal-title":"Biomater. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Narayanaswamy, R., and Torchilin, V.P. (2019). Hydrogels and Their Applications in Targeted Drug Delivery. Molecules, 24.","DOI":"10.3390\/molecules24030603"},{"key":"ref_10","unstructured":"L\u0103cr\u0103mioara, P., Mihaela Violeta, G., and Cristina-Elena, D.-P. (2018). Hydrogels, IntechOpen. Chapter 2."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vasudevan, D., Sreekumari, S., and Vaidyanathan, K. (2017). Textbook of Biochemistry for Medical Students, Jaypee Brothers Medical Publishers.","DOI":"10.5005\/jp\/books\/13014_49"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2013006955","article-title":"Peptide and protein delivery using new drug delivery systems","volume":"30","author":"Jain","year":"2013","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"ref_13","unstructured":"Tekade, R.K. (2019). Basic Fundamentals of Drug Delivery, Academic Press."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"de la Torre, B.G., and Albericio, F. (2020). The Pharmaceutical Industry in 2019. An Analysis of FDA Drug Approvals from the Perspective of Molecules. Molecules, 25.","DOI":"10.3390\/molecules25030745"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/d41573-020-00001-7","article-title":"2019 FDA drug approvals","volume":"19","author":"Mullard","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/d41573-021-00002-0","article-title":"2020 FDA drug approvals","volume":"20","author":"Mullard","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Martins, A.C., Albericio, F., and de la Torre, B.G. (2023). FDA Approvals of Biologics in 2022. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051434"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.yexcr.2011.02.013","article-title":"Introduction to current and future protein therapeutics: A protein engineering perspective","volume":"317","author":"Carter","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"de la Torre, B.G., and Albericio, F. (2022). The Pharmaceutical Industry in 2021. An Analysis of FDA Drug Approvals from the Perspective of Molecules. Molecules, 27.","DOI":"10.3390\/molecules27031075"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrd2399","article-title":"Protein therapeutics: A summary and pharmacological classification","volume":"7","author":"Leader","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Timofeev, V., and Samygina, V. (2023). Protein Crystallography: Achievements and Challenges. Crystals, 13.","DOI":"10.3390\/cryst13010071"},{"key":"ref_22","unstructured":"Voet, D., and Voet, J.G. (2010). Biochemistry, John Wiley & Sons. [4th ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liang, W., Pan, H.W., Vllasaliu, D., and Lam, J.K.W. (2020). Pulmonary Delivery of Biological Drugs. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111025"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Awwad, S., and Angkawinitwong, U. (2018). Overview of antibody drug delivery. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030083"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1124\/dmd.119.086488","article-title":"Mechanisms Influencing the Pharmacokinetics and Disposition of Monoclonal Antibodies and Peptides","volume":"47","year":"2019","journal-title":"Drug Metab. Dispos."},{"key":"ref_26","unstructured":"Mitra, A.K., Cholkar, K., and Mandal, A. (2017). Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices, Elsevier."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nrd1067","article-title":"Challenges for the oral delivery of macromolecules","volume":"2","author":"Goldberg","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","unstructured":"Ali Demir, S. (2016). Smart Drug Delivery System, IntechOpen. Chapter 8."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijpharm.2013.02.030","article-title":"Approaches for enhancing oral bioavailability of peptides and proteins","volume":"447","author":"Renukuntla","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4331\/wjbc.v3.i4.73","article-title":"Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges","volume":"3","author":"Vugmeyster","year":"2012","journal-title":"World J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1080\/03639045.2019.1628770","article-title":"A review on parenteral delivery of peptides and proteins","volume":"45","author":"Jain","year":"2019","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ibeanu, N., Egbu, R., Onyekuru, L., Javaheri, H., Khaw, P.T., Williams, G.R., Brocchini, S., and Awwad, S. (2020). Injectables and Depots to Prolong Drug Action of Proteins and Peptides. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12100999"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1007\/s12325-019-01101-6","article-title":"Subcutaneous Injection of Drugs: Literature Review of Factors Influencing Pain Sensation at the Injection Site","volume":"36","author":"Usach","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/jphp.12731","article-title":"Challenges for the pharmaceutical technical development of protein coformulations","volume":"70","author":"Mueller","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1055\/s-0034-1368173","article-title":"Subcutaneous Administration of Monoclonal Antibodies in Oncology","volume":"74","author":"Jackisch","year":"2014","journal-title":"Geburtshilfe Frauenheilkd"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/19420862.2015.1128606","article-title":"Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development","volume":"8","author":"Tomar","year":"2016","journal-title":"MAbs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1124\/dmd.111.043604","article-title":"Lymphatic transport and catabolism of therapeutic proteins after subcutaneous administration to rats and dogs","volume":"40","author":"Wang","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1016\/j.xphs.2017.05.030","article-title":"Perspectives on Subcutaneous Route of Administration as an Immunogenicity Risk Factor for Therapeutic Proteins","volume":"106","author":"Hamuro","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1023\/A:1015880819328","article-title":"Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration","volume":"7","author":"Supersaxo","year":"1990","journal-title":"Pharm. Res."},{"key":"ref_40","unstructured":"(2023, August 23). FDA: Novel Drug Approvals for 2017, Available online: https:\/\/www.fda.gov\/drugs\/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products\/novel-drug-approvals-2017."},{"key":"ref_41","unstructured":"(2023, August 23). FDA: Novel Drug Approvals for 2018, Available online: https:\/\/www.fda.gov\/drugs\/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products\/novel-drug-approvals-2018."},{"key":"ref_42","unstructured":"(2023, August 23). FDA: Novel Drug Approvals for 2019, Available online: https:\/\/www.fda.gov\/drugs\/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products\/novel-drug-approvals-2019."},{"key":"ref_43","unstructured":"(2023, August 23). FDA: Novel Drugs Approvals for 2020, Available online: https:\/\/www.fda.gov\/drugs\/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products\/novel-drug-approvals-2020."},{"key":"ref_44","unstructured":"(2023, August 23). FDA: Novel Drug Approvals for 2021, Available online: https:\/\/www.fda.gov\/drugs\/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products\/novel-drug-approvals-2021."},{"key":"ref_45","unstructured":"(2023, August 23). FDA: Novel Drug Approvals for 2022, Available online: https:\/\/www.fda.gov\/drugs\/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products\/novel-drug-approvals-2022."},{"key":"ref_46","unstructured":"(2023, August 23). FDA: Novel Drug Approvals for 2023, Available online: https:\/\/www.fda.gov\/drugs\/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products\/novel-drug-approvals-2023."},{"key":"ref_47","unstructured":"Tekade, R.K. (2018). Dosage Form Design Consideration, Academic Press."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.apsb.2019.01.004","article-title":"Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides\/proteins","volume":"9","author":"Han","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ejpb.2016.11.034","article-title":"Food, gastrointestinal pH, and models of oral drug absorption","volume":"112","author":"Abuhelwa","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"119488","DOI":"10.1016\/j.ijpharm.2020.119488","article-title":"Oral delivery of protein-based therapeutics: Gastroprotective strategies, physiological barriers and in vitro permeability prediction","volume":"585","author":"Wright","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41578-019-0156-6","article-title":"Materials for oral delivery of proteins and peptides","volume":"5","author":"Brown","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1002\/jps.21961","article-title":"Paracellular porosity and pore size of the human intestinal epithelium in tissue and cell culture models","volume":"99","author":"Linnankoski","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1016\/j.apsb.2021.04.001","article-title":"Oral delivery of proteins and peptides: Challenges, status quo and future perspectives","volume":"11","author":"Zhu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/17425247.2016.1206074","article-title":"Emerging delivery platforms for mucosal administration of biopharmaceuticals: A critical update on nasal, pulmonary and oral routes","volume":"14","author":"Thwala","year":"2017","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrd.2018.183","article-title":"Non-invasive delivery strategies for biologics","volume":"18","author":"Anselmo","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_57","unstructured":"Balc\u00e3o, V., and Moutinho, C. (2013). Encyclopedia of Pharmaceutical Science and Technology, Informa Healthcare."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1208\/s12249-020-01675-3","article-title":"Relationship Between Geometric and Aerodynamic Particle Size Distributions in the Formulation of Solution and Suspension Metered-Dose Inhalers","volume":"21","author":"Yoshida","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1089\/jamp.2010.0836","article-title":"The particle has landed\u2014Characterizing the fate of inhaled pharmaceuticals","volume":"23","author":"Patton","year":"2010","journal-title":"J. Aerosol. Med. Pulm. Drug Deliv."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Matthews, A.A., Ee, P.L.R., and Ge, R. (2020). Developing inhaled protein therapeutics for lung diseases. Mol. Biomed., 1.","DOI":"10.1186\/s43556-020-00014-z"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.xphs.2015.10.025","article-title":"Pulmonary Delivery of the Kv1.3-Blocking Peptide HsTX1[R14A] for the Treatment of Autoimmune Diseases","volume":"105","author":"Jin","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1513\/pats.200409-049TA","article-title":"The lungs as a portal of entry for systemic drug delivery","volume":"1","author":"Patton","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/j.drudis.2019.05.006","article-title":"Therapeutic implications of nanomedicine for ocular drug delivery","volume":"24","author":"Meng","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Bachu, R.D., Chowdhury, P., Al-Saedi, Z.H.F., Karla, P.K., and Boddu, S.H.S. (2018). Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10010028"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5497\/wjp.v2.i2.47","article-title":"Ocular drug delivery systems: An overview","volume":"2","author":"Patel","year":"2013","journal-title":"World J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4103\/ijo.IJO_646_17","article-title":"Anatomy of cornea and ocular surface","volume":"66","author":"Sridhar","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"27835","DOI":"10.1039\/D0RA04971A","article-title":"Nanocarriers for ocular drug delivery: Current status and translational opportunity","volume":"10","author":"Gorantla","year":"2020","journal-title":"RSC Adv."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1080\/21691401.2018.1430695","article-title":"Passive delivery of protein drugs through transdermal route","volume":"46","author":"Chaulagain","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.4155\/tde.15.60","article-title":"Transdermal delivery of biopharmaceuticals: Dream or reality?","volume":"6","author":"Katikaneni","year":"2015","journal-title":"Ther. Deliv."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1461-5347(00)00295-9","article-title":"Transdermal drug delivery: Overcoming the skin\u2019s barrier function","volume":"3","author":"Naik","year":"2000","journal-title":"Pharm. Sci. Technol. Today"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1208\/s12248-017-0054-z","article-title":"Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes","volume":"19","author":"Morales","year":"2017","journal-title":"AAPS J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e202214795","DOI":"10.1002\/anie.202214795","article-title":"Recent Advances in Oral and Transdermal Protein Delivery Systems","volume":"62","author":"Yang","year":"2023","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_73","unstructured":"Koussoroplis, S.-J., and Vanbever, R. (2013). Encyclopedia of Pharmaceutical Science and Technology, Taylor and Francis. [4th ed.]."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.addr.2018.01.008","article-title":"Ocular delivery of proteins and peptides: Challenges and novel formulation approaches","volume":"126","author":"Mandal","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_75","unstructured":"(2023, August 23). FDA: FDA Approves First Drug for Neurotrophic Keratitis, a Rare Eye Disease, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-drug-neurotrophic-keratitis-rare-eye-disease."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1177\/193229681000400302","article-title":"Evolution of diabetes insulin delivery devices","volume":"4","author":"Selam","year":"2010","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wells, C.M., Harris, M., Choi, L., Murali, V.P., Guerra, F.D., and Jennings, J.A. (2019). Stimuli-Responsive Drug Release from Smart Polymers. J. Funct. Biomater., 10.","DOI":"10.3390\/jfb10030034"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Raza, F., Zafar, H., Zhu, Y., Ren, Y., Ullah, A., Khan, A.U., He, X., Han, H., Aquib, M., and Boakye-Yiadom, K.O. (2018). A Review on Recent Advances in Stabilizing Peptides\/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10010016"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Luna, V.H., and Gonz\u00e1lez-Reynoso, O. (2018). Encapsulation of Biological Agents in Hydrogels for Therapeutic Applications. Gels, 4.","DOI":"10.3390\/gels4030061"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Shymborska, Y., Budkowski, A., Raczkowska, J., Donchak, V., Melnyk, Y., Vasiichuk, V., and Stetsyshyn, Y. (2023). Switching it Up: The Promise of Stimuli-Responsive Polymer Systems in Biomedical Science. Chem. Rec., e202300217.","DOI":"10.1002\/tcr.202300217"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Mahlumba, P., Choonara, Y.E., Kumar, P., du Toit, L.C., and Pillay, V. (2016). Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery. Molecules, 21.","DOI":"10.3390\/molecules21081002"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Chatterjee, S., and Chi-Leung Hui, P. (2019). Review of Stimuli-Responsive Polymers in Drug Delivery and Textile Application. Molecules, 24.","DOI":"10.3390\/molecules24142547"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Elnashar, M. (2010). Biopolymers, IntechOpen. Chapter 3.","DOI":"10.5772\/286"},{"key":"ref_84","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_85","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1248\/cpb.c17-00068","article-title":"Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics","volume":"65","author":"Hatakeyama","year":"2017","journal-title":"Chem. Pharm. Bull."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fmats.2020.00073","article-title":"Hybrid Thermo-Responsive Polymer Systems and Their Biomedical Applications","volume":"7","author":"Sarwan","year":"2020","journal-title":"Front. Mater."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.ijpharm.2014.06.029","article-title":"Thermoresponsive polymers: Insights into decisive hydrogel characteristics, mechanisms of gelation, and promising biomedical applications","volume":"472","author":"Kristl","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_88","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_89","doi-asserted-by":"crossref","unstructured":"Chatterjee, S., and Hui, P.C. (2021). Review of Applications and Future Prospects of Stimuli-Responsive Hydrogel Based on Thermo-Responsive Biopolymers in Drug Delivery Systems. Polymers, 13.","DOI":"10.3390\/polym13132086"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.apsb.2014.02.005","article-title":"Smart polymers for the controlled delivery of drugs\u2014A concise overview","volume":"4","author":"Rijo","year":"2014","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1016\/j.ddtec.2012.05.001","article-title":"Smart polymers for peptide and protein parenteral sustained delivery","volume":"9","author":"Oak","year":"2012","journal-title":"Drug Discov. Today Technol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1177\/0391398818765323","article-title":"Biopolymer-based strategies in the design of smart medical devices and artificial organs","volume":"41","author":"Altomare","year":"2018","journal-title":"Int. J. Artif. Organs"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"032004","DOI":"10.1088\/2515-7639\/ab1af5","article-title":"Bio-responsive smart polymers and biomedical applications","volume":"2","author":"Zhang","year":"2019","journal-title":"J. Phys. Mater."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5908","DOI":"10.1039\/c0sm01307b","article-title":"Stimulus responsive nanogels for drug delivery","volume":"7","author":"Zha","year":"2011","journal-title":"Soft Matter"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Andrade, F., Roca-Melendres, M.M., Dur\u00e1n-Lara, E.F., Rafael, D., and Schwartz, S. (2021). Stimuli-Responsive Hydrogels for Cancer Treatment: The Role of pH, Light, Ionic Strength and Magnetic Field. Cancers, 13.","DOI":"10.3390\/cancers13051164"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Rizwan, M., Yahya, R., Hassan, A., Yar, M., Azzahari, A.D., Selvanathan, V., Sonsudin, F., and Abouloula, C.N. (2017). pH Sensitive Hydrogels in Drug Delivery: Brief History, Properties, Swelling, and Release Mechanism, Material Selection and Applications. Polymers, 9.","DOI":"10.3390\/polym9040137"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1517\/17425247.2013.821978","article-title":"pH- and ion-sensitive polymers for drug delivery","volume":"10","author":"Yoshida","year":"2013","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Lynch, C.R., Kondiah, P.P.D., Choonara, Y.E., du Toit, L.C., Ally, N., and Pillay, V. (2020). Hydrogel Biomaterials for Application in Ocular Drug Delivery. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00228"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.eurpolymj.2017.12.004","article-title":"Recent advances in smart hydrogels for biomedical applications: From self-assembly to functional approaches","volume":"99","author":"Ferreira","year":"2018","journal-title":"Eur. Polym. J."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"El-Husseiny, H.M., Mady, E.A., El-Dakroury, W.A., Doghish, A.S., and Tanaka, R. (2023). Stimuli-responsive hydrogels: Smart state of-the-art platforms for cardiac tissue engineering. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1174075"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"11723","DOI":"10.1039\/c2sm26572a","article-title":"The Effect of Ionic Strength on the Mechanical, Structural and Transport Properties of Peptide Hydrogels","volume":"8","author":"Feng","year":"2012","journal-title":"Soft Matter"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rudko, M., Urbaniak, T., and Musia\u0142, W. (2021). Recent Developments in Ion-Sensitive Systems for Pharmaceutical Applications. Polymers, 13.","DOI":"10.3390\/polym13101641"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1002\/jbm.a.37255","article-title":"Alginate hydrogels functionalized with \u03b2-cyclodextrin as a local paclitaxel delivery system","volume":"109","author":"Omtvedt","year":"2021","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Zhang, H., Cheng, J., and Ao, Q. (2021). Preparation of Alginate-Based Biomaterials and Their Applications in Biomedicine. Mar. Drugs, 19.","DOI":"10.3390\/md19050264"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1700801","DOI":"10.1002\/adhm.201700801","article-title":"Biomolecule-Responsive Hydrogels in Medicine","volume":"6","author":"Sharifzadeh","year":"2017","journal-title":"Adv. Healthc. Mater."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Cao, J., Yuan, P., Wu, B., Liu, Y., and Hu, C. (2023). Advances in the Research and Application of Smart-Responsive Hydrogels in Disease Treatment. Gels, 9.","DOI":"10.3390\/gels9080662"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Zhao, L., Wang, L., Zhang, Y., Xiao, S., Bi, F., Zhao, J., Gai, G., and Ding, J. (2017). Glucose Oxidase-Based Glucose-Sensitive Drug Delivery for Diabetes Treatment. Polymers, 9.","DOI":"10.3390\/polym9070255"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Mantha, S., Pillai, S., Khayambashi, P., Upadhyay, A., Zhang, Y., Tao, O., Pham, H.M., and Tran, S.D. (2019). Smart Hydrogels in Tissue Engineering and Regenerative Medicine. Materials, 12.","DOI":"10.3390\/ma12203323"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2147\/IJN.S284357","article-title":"Bioresponsive Functional Phenylboronic Acid-Based Delivery System as an Emerging Platform for Diabetic Therapy","volume":"16","author":"Ma","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Morariu, S. (2023). Advances in the Design of Phenylboronic Acid-Based Glucose-Sensitive Hydrogels. Polymers, 15.","DOI":"10.3390\/polym15030582"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"122578","DOI":"10.1016\/j.matchemphys.2019.122578","article-title":"Synthesis of poly(acrylamide)-based hydrogel for bio-sensing of hepatitis B core antigen","volume":"243","author":"Lim","year":"2020","journal-title":"Mater. Chem. Phys."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Li, X., Duan, L., Kong, M., Wen, X., Guan, F., and Ma, S. (2022). Applications and Mechanisms of Stimuli-Responsive Hydrogels in Traumatic Brain Injury. Gels, 8.","DOI":"10.3390\/gels8080482"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0169-409X(01)00203-4","article-title":"Environment-sensitive hydrogels for drug delivery","volume":"53","author":"Qiu","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3389\/fmed.2020.00456","article-title":"Design, Bioanalytical, and Biomedical Applications of Aptamer-Based Hydrogels","volume":"7","author":"Di","year":"2020","journal-title":"Front. Med."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Chang, D., Ma, Y., Xu, X., Xie, J., and Ju, S. (2021). Stimuli-Responsive Polymeric Nanoplatforms for Cancer Therapy. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.707319"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Ran, B., Xie, X., Gu, W., Ye, X., and Liao, J. (2022). Developments on the Smart Hydrogel-Based Drug Delivery System for Oral Tumor Therapy. Gels, 8.","DOI":"10.3390\/gels8110741"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1177\/1535370216647186","article-title":"Enzyme-responsive polymer hydrogels for therapeutic delivery","volume":"241","author":"Chandrawati","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1039\/C2BM00041E","article-title":"Enzyme responsive materials: Design strategies and future developments","volume":"1","author":"Zelzer","year":"2013","journal-title":"Biomater. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3390\/polym3020779","article-title":"Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems","volume":"3","author":"Bonacucina","year":"2011","journal-title":"Polymers"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"121298","DOI":"10.1016\/j.carbpol.2023.121298","article-title":"Recent advances in 3D printed cellulose-based wound dressings: A review on in vitro and in vivo achievements","volume":"321","author":"Concheiro","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives and Nutrient Sources Added to Food (ANS), Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Dusemund, B., Filipi\u010d, M., Frutos, M.J., Galtier, P., and Gundert-Remy, U. (2018). Safety of low-substituted hydroxypropyl cellulose (L-HPC) to be used as a food additive in food supplements in tablet form. EFSA J., 16, e05062.","DOI":"10.2903\/j.efsa.2018.5062"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Piqu\u00e9, N., G\u00f3mez-Guill\u00e9n, M.D.C., and Montero, M.P. (2018). Xyloglucan, a Plant Polymer with Barrier Protective Properties over the Mucous Membranes: An Overview. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030673"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1016\/j.fct.2007.07.011","article-title":"Safety assessment of hydroxypropyl methylcellulose as a food ingredient","volume":"45","author":"Burdock","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Yang, L., Fan, X., Zhang, J., and Ju, J. (2020). Preparation and Characterization of Thermoresponsive Poly(N-Isopropylacrylamide) for Cell Culture Applications. Polymers, 12.","DOI":"10.3390\/polym12020389"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Iglesias, N., Galbis, E., Romero-Azogil, L., Benito, E., Lucas, R., Garc\u00eda-Mart\u00edn, M.G., and de-Paz, M.V. (2020). In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070636"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Mathaba, M., and Daramola, M.O. (2020). Effect of Chitosan\u2019s Degree of Deacetylation on the Performance of PES Membrane Infused with Chitosan during AMD Treatment. Membranes, 10.","DOI":"10.3390\/membranes10030052"},{"key":"ref_127","first-page":"1058","article-title":"Phthaloylation of cellulose acetate in acetic acid and acetone Media","volume":"14","author":"Olaru","year":"2005","journal-title":"Iran. Polym. J."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1021\/acs.molpharmaceut.1c00474","article-title":"Advanced Delivery Systems Based on Lysine or Lysine Polymers","volume":"18","author":"Manouchehri","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/macp.201000773","article-title":"Free Radical Polymerization Kinetics of Vinylsulfonic Acid and Highly Acidic Properties of its Polymer","volume":"212","author":"Okayasu","year":"2011","journal-title":"Macromol. Chem. Phys."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.progpolymsci.2008.05.002","article-title":"Exploration of polymethacrylate structure-property correlations: Advances towards combinatorial and high-throughput methods for biomaterials discovery","volume":"33","author":"Holmes","year":"2008","journal-title":"Prog. Polym. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ijpharm.2014.03.038","article-title":"Application of gellan gum in pharmacy and medicine","volume":"466","author":"Froelich","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Jadav, M., Pooja, D., Adams, D.J., and Kulhari, H. (2023). Advances in Xanthan Gum-Based Systems for the Delivery of Therapeutic Agents. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020402"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Torres, M.D., Fl\u00f3rez-Fern\u00e1ndez, N., and Dom\u00ednguez, H. (2019). Integral Utilization of Red Seaweed for Bioactive Production. Mar. Drugs, 17.","DOI":"10.3390\/md17060314"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Chandel, V., Biswas, D., Roy, S., Vaidya, D., Verma, A., and Gupta, A. (2022). Current Advancements in Pectin: Extraction, Properties and Multifunctional Applications. Foods, 11.","DOI":"10.3390\/foods11172683"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/1475-2859-10-99","article-title":"Microbial production of hyaluronic acid: Current state, challenges, and perspectives","volume":"10","author":"Liu","year":"2011","journal-title":"Microb. Cell Fact."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"31203","DOI":"10.1021\/acsomega.1c04856","article-title":"Factorial Design to Optimize Dextran Production by the Native Strain Leuconostoc mesenteroides SF3","volume":"6","author":"Guarin","year":"2021","journal-title":"ACS Omega"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.polymer.2016.10.015","article-title":"Synthesis of heterobifunctional polyethylene glycols: Polymerization from functional initiators","volume":"105","author":"Vojkovsky","year":"2016","journal-title":"Polymer"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Jurko, L., Bra\u010di\u010d, M., Hribernik, S., Makuc, D., Plavec, J., Jerenec, F., \u017dabkar, S., Gubeljak, N., \u0160tern, A., and Kargl, R. (2021). Succinylation of Polyallylamine: Influence on Biological Efficacy and the Formation of Electrospun Fibers. Polymers, 13.","DOI":"10.3390\/polym13172840"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Municoy, S., \u00c1lvarez Echaz\u00fa, M.I., Antezana, P.E., Galdop\u00f3rpora, J.M., Olivetti, C., Mebert, A.M., Foglia, M.L., Tuttolomondo, M.V., Alvarez, G.S., and Hardy, J.G. (2020). Stimuli-Responsive Materials for Tissue Engineering and Drug Delivery. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134724"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/j.chempr.2018.07.002","article-title":"Multi-Stimuli-Responsive Polymer Particles, Films, and Hydrogels for Drug Delivery","volume":"4","author":"Fu","year":"2018","journal-title":"Chem"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1016\/j.biomaterials.2013.01.084","article-title":"Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery","volume":"34","author":"Cheng","year":"2013","journal-title":"Biomaterials"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Pham, S.H., Choi, Y., and Choi, J. (2020). Stimuli-Responsive Nanomaterials for Application in Antitumor Therapy and Drug Delivery. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070630"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.molliq.2018.04.002","article-title":"pH-responsive alginate-based hydrogels for protein delivery","volume":"262","author":"Lima","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.polymer.2016.12.039","article-title":"Temperature and pH-sensitive injectable hydrogels based on poly(sulfamethazine carbonate urethane) for sustained delivery of cationic proteins","volume":"109","author":"Phan","year":"2017","journal-title":"Polymer"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ijbiomac.2020.02.179","article-title":"Protein nanocomposites: Special inferences to lysozyme based nanomaterials","volume":"151","author":"Sarkar","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1080\/10717544.2017.1333173","article-title":"Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus","volume":"24","author":"Xu","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"17531","DOI":"10.1021\/acsomega.0c02009","article-title":"In Situ Forming Injectable Thermoresponsive Hydrogels for Controlled Delivery of Biomacromolecules","volume":"5","author":"Dutta","year":"2020","journal-title":"ACS Omega"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"8147","DOI":"10.1021\/acs.iecr.1c01277","article-title":"Injectable Temperature\/Glucose Dual-Responsive Hydrogels for Controlled Release of Insulin","volume":"60","author":"Hu","year":"2021","journal-title":"Ind. Eng. Chem. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13098-019-0469-z","article-title":"Evaluation of sexual dysfunction and female sexual dysfunction indicators in women with type 2 diabetes: A systematic review and meta-analysis","volume":"11","author":"Rahmanian","year":"2019","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.actbio.2021.01.007","article-title":"Glucose-responsive hydrogel enhances the preventive effect of insulin and liraglutide on diabetic nephropathy of rats","volume":"122","author":"Tong","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1021\/acs.biomac.5b00193","article-title":"Anisamide-Decorated pH-Sensitive Degradable Chimaeric Polymersomes Mediate Potent and Targeted Protein Delivery to Lung Cancer Cells","volume":"16","author":"Lu","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_152","first-page":"1361","article-title":"Granzyme B-induced apoptosis in cancer cells and its regulation (review)","volume":"37","author":"Rousalova","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.2147\/IJN.S253990","article-title":"Engineering Thermo-pH Dual Responsive Hydrogel for Enhanced Tumor Accumulation, Penetration, and Chemo-Protein Combination Therapy","volume":"15","author":"Pang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"eaau5480","DOI":"10.1126\/science.aau5480","article-title":"Antimicrobial peptides: Application informed by evolution","volume":"368","author":"Lazzaro","year":"2020","journal-title":"Science"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Mahlapuu, M., H\u00e5kansson, J., Ringstad, L., and Bj\u00f6rn, C. (2016). Antimicrobial Peptides: An Emerging Category of Therapeutic Agents. Front. Cell Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00194"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.ijbiomac.2020.07.011","article-title":"Antimicrobial peptides-loaded smart chitosan hydrogel: Release behavior and antibacterial potential against antibiotic resistant clinical isolates","volume":"164","author":"Rezaei","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Nie, L., Chang, P., Sun, M., Huo, H., Zhang, C., Ji, C., Wei, X., Zhou, Q., Guo, P., and Yuan, H. (2018). Composite Hydrogels with the Simultaneous Release of VEGF and MCP-1 for Enhancing Angiogenesis for Bone Tissue Engineering Applications. Appl. Sci., 8.","DOI":"10.3390\/app8122438"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1021\/acsbiomaterials.8b00646","article-title":"Dual Stimuli-Responsive Nanoparticle-Incorporated Hydrogels as an Oral Insulin Carrier for Intestine-Targeted Delivery and Enhanced Paracellular Permeation","volume":"4","author":"Liu","year":"2018","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s10965-019-1953-8","article-title":"pH-responsive hydrogels based on the self-assembly of short polypeptides for controlled release of peptide and protein drugs","volume":"26","author":"Bao","year":"2019","journal-title":"J. Polym. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.actbio.2017.01.016","article-title":"pH-sensitive peptide hydrogel for glucose-responsive insulin delivery","volume":"51","author":"Li","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1089\/ten.tea.2020.0124","article-title":"Degradation-Dependent Protein Release from Enzyme Sensitive Injectable Glycol Chitosan Hydrogel","volume":"27","author":"Gohil","year":"2021","journal-title":"Tissue Eng. Part A"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1021\/ar900035f","article-title":"Soluble Polymer Carriers for the Treatment of Cancer: The Importance of Molecular Architecture","volume":"42","author":"Fox","year":"2009","journal-title":"Acc. Chem. Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"154201","DOI":"10.1016\/j.apsusc.2022.154201","article-title":"Protein corona of SiO2 nanoparticles with grafted thermoresponsive copolymers: Calorimetric insights on factors affecting entropy vs. enthalpy-driven associations","volume":"601","author":"Nastyshyn","year":"2022","journal-title":"Appl. Surf. Sci."}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/9\/10\/802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:02:03Z","timestamp":1760130123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/9\/10\/802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,6]]},"references-count":163,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["gels9100802"],"URL":"https:\/\/doi.org\/10.3390\/gels9100802","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,6]]}}}