{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:41:16Z","timestamp":1791218476421,"version":"4.1.0"},"reference-count":140,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T00:00:00Z","timestamp":1762560000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T00:00:00Z","timestamp":1762560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Protein J"],"DOI":"10.1007\/s10930-025-10302-8","type":"journal-article","created":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T16:56:35Z","timestamp":1762620995000},"page":"8-21","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Strategic Approaches for Overcoming Peptide and Protein Drug Limitations"],"prefix":"10.1007","volume":"45","author":[{"given":"Mahsa","family":"Cheshomi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikta","family":"Shobeiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amineh Sadat","family":"Tajani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahman","family":"Khameneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,8]]},"reference":[{"issue":"1","key":"10302_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.56808\/3027-7922.2165","volume":"34","author":"BS Sekhon","year":"2010","unstructured":"Sekhon BS (2010) Biopharmaceuticals: an overview. Thai J Pharm Sci 34(1):1\u201319","journal-title":"Thai J Pharm Sci"},{"key":"10302_CR2","first-page":"1","volume":"20","author":"KB Liew","year":"2023","unstructured":"Liew KB, Lee SK, Ming LC, Uddin AH, Sarker ZI, Chew YL, Kee PE (2023) Biopharmaceuticals: a review of their development and contribution to healthcare. Biomed Biopharm Res 20:1\u201325","journal-title":"Biomed Biopharm Res"},{"issue":"4","key":"10302_CR3","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nrd1695","volume":"4","author":"S Frokjaer","year":"2005","unstructured":"Frokjaer S, Otzen DE (2005) Protein drug stability: a formulation challenge. Nat Rev Drug Discov 4(4):298\u2013306","journal-title":"Nat Rev Drug Discov"},{"issue":"8","key":"10302_CR4","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1517\/17425247.2014.917077","volume":"11","author":"AL Smart","year":"2014","unstructured":"Smart AL, Gaisford S, Basit AW (2014) Oral peptide and protein delivery: intestinal obstacles and commercial prospects. Expert Opin Drug Deliv 11(8):1323\u20131335","journal-title":"Expert Opin Drug Deliv"},{"issue":"6","key":"10302_CR5","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3109\/10717544.2013.819611","volume":"20","author":"S Gupta","year":"2013","unstructured":"Gupta S, Jain A, Chakraborty M, Sahni JK, Ali J, Dang S (2013) Oral delivery of therapeutic proteins and peptides: a review on recent developments. Drug Deliv 20(6):237\u2013246","journal-title":"Drug Deliv"},{"issue":"1","key":"10302_CR6","first-page":"1","volume":"12","author":"L Andrew","year":"2022","unstructured":"Andrew L (2022) Lewis, Nicholas McEntee, Justin Holland, and Asma Patel, development and approval of rybelsus (oral semaglutide): ushering in a new era in peptide delivery. Drug Deliv Transl Res 12(1):1\u20136","journal-title":"Drug Deliv Transl Res"},{"issue":"1","key":"10302_CR7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/pharmaceutics16010047","volume":"16","author":"D Asano","year":"2023","unstructured":"Asano D, Takakusa H, Nakai D (2023) Oral absorption of middle-to-large molecules and its improvement, with a focus on new modality drugs. Pharmaceutics 16(1):47","journal-title":"Pharmaceutics"},{"issue":"1","key":"10302_CR8","first-page":"130","volume":"5","author":"\u6d69 \u677f\u6771","year":"2022","unstructured":"\u677f\u6771\u6d69 (2022) Effective oral formulation of semaglutide (Rybelsus) for diabetes and obesity due to absorption enhancer development. Int J Endocrinol Diabetes 5(1):130","journal-title":"Int J Endocrinol Diabetes"},{"issue":"3","key":"10302_CR9","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nrd1033","volume":"2","author":"JM Harris","year":"2003","unstructured":"Harris JM, Chess RB (2003) Effect of PEGylation on pharmaceuticals. Nature rev Drug discov 2(3):214\u2013221","journal-title":"Nature rev Drug discov"},{"issue":"3","key":"10302_CR10","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/S0168-3659(03)00194-9","volume":"90","author":"VR Sinha","year":"2003","unstructured":"Sinha VR, Trehan A (2003) Biodegradable microspheres for protein delivery. J Control Release 90(3):261\u2013280","journal-title":"J Control Release"},{"issue":"Pt B","key":"10302_CR11","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.addr.2016.04.001","volume":"106","author":"Z Niu","year":"2016","unstructured":"Niu Z, Conejos-S\u00e1nchez I, Griffin BT, O\u2019Driscoll CM, Alonso MJ (2016) Lipid-based nanocarriers for oral peptide delivery. Adv Drug Deliv Rev 106(Pt B):337\u2013354","journal-title":"Adv Drug Deliv Rev"},{"issue":"1","key":"10302_CR12","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.peptides.2009.10.002","volume":"31","author":"ML Tan","year":"2010","unstructured":"Tan ML, Choong PF, Dass CR (2010) Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery. Peptides 31(1):184\u2013193","journal-title":"Peptides"},{"issue":"2","key":"10302_CR13","doi-asserted-by":"publisher","first-page":"107","DOI":"10.4161\/mabs.3.2.14785","volume":"3","author":"A Beck","year":"2011","unstructured":"Beck A (2011) Biosimilar, biobetter and next generation therapeutic antibodies. MAbs 3(2):107\u2013110","journal-title":"MAbs"},{"issue":"1","key":"10302_CR14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.2165\/11530550-000000000-00000","volume":"24","author":"RJ Sol\u00e1","year":"2010","unstructured":"Sol\u00e1 RJ, Griebenow K (2010) Glycosylation of therapeutic proteins: an effective strategy to optimize efficacy. BioDrugs 24(1):9\u201321","journal-title":"BioDrugs"},{"key":"10302_CR15","unstructured":"Available from: protein therapeutics market size, share, competitive landscape and trend analysis report by product and application: global opportunity analysis and industry forecast, 2021\u20132030. Retrieved from https:\/\/www.alliedmarketresearch.com\/protein-therapeutics-market"},{"key":"10302_CR16","unstructured":"Global peptide therapeutics market outlook 2031. 2022; Available from: https:\/\/www.transparencymarketresearch.com\/peptide-therapeutics-market.html"},{"key":"10302_CR17","unstructured":"Peptide therapeutics market size, share & trends-2033 2021; Available from: https:\/\/www.futuremarketinsights.com\/reports\/peptide-therapeutics-market"},{"issue":"1","key":"10302_CR18","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/cbdd.12055","volume":"81","author":"JC David","year":"2013","unstructured":"David JC, David PF, Spiros L, David P (2013) The future of peptide-based drugs. Chem Biol Drug Des 81(1):136\u2013147","journal-title":"Chem Biol Drug Des"},{"issue":"20","key":"10302_CR19","doi-asserted-by":"publisher","first-page":"7165","DOI":"10.3390\/molecules28207165","volume":"28","author":"G Rossino","year":"2023","unstructured":"Rossino G, Marchese E, Galli G, Verde F, Finizio M, Serra M, Linciano P, Collina S (2023) Peptides as therapeutic agents: challenges and opportunities in the green transition era. Molecules 28(20):7165","journal-title":"Molecules"},{"issue":"1\u20133","key":"10302_CR20","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0169-409X(00)00144-7","volume":"46","author":"T Arakawa","year":"2001","unstructured":"Arakawa T, Prestrelski SJ, Kenney WC, Carpenter JF (2001) Factors affecting short-term and long-term stabilities of proteins. Adv Drug Deliv Rev 46(1\u20133):307\u2013326","journal-title":"Adv Drug Deliv Rev"},{"issue":"2","key":"10302_CR21","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1080\/08916930601165180","volume":"40","author":"HA Doyle","year":"2007","unstructured":"Doyle HA, Gee RJ, Mamula MJ (2007) Altered immunogenicity of isoaspartate containing proteins. Autoimmunity 40(2):131\u2013137","journal-title":"Autoimmunity"},{"issue":"6","key":"10302_CR22","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1111\/j.1399-3011.1987.tb03390.x","volume":"30","author":"S Clarke","year":"1987","unstructured":"Clarke S (1987) Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins. Int J Pept Protein Res 30(6):808\u2013821","journal-title":"Int J Pept Protein Res"},{"issue":"12","key":"10302_CR23","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1002\/jps.1165","volume":"90","author":"LP Stratton","year":"2001","unstructured":"Stratton LP, Kelly RM, Rowe J, Shively JE, Smith DD, Carpenter JF, Manning MC (2001) Controlling deamidation rates in a model peptide: effects of temperature, peptide concentration, and additives. J Pharm Sci 90(12):2141\u20132148","journal-title":"J Pharm Sci"},{"issue":"8\u20139","key":"10302_CR24","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/S0141-0229(01)00428-8","volume":"29","author":"M Miroliaei","year":"2001","unstructured":"Miroliaei M, Nemat-Gorgani M (2001) Sugars protect native and apo yeast alcohol dehydrogenase against irreversible thermoinactivation. Enzyme Microb Technol 29(8\u20139):554\u2013559","journal-title":"Enzyme Microb Technol"},{"issue":"10","key":"10302_CR25","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/nrendo.2016.105","volume":"12","author":"P Zimmet","year":"2016","unstructured":"Zimmet P, Alberti KG, Magliano DJ, Bennett PH (2016) Diabetes mellitus statistics on prevalence and mortality: facts and fallacies. Nat Rev Endocrinol 12(10):616\u2013622","journal-title":"Nat Rev Endocrinol"},{"issue":"2","key":"10302_CR26","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bbapap.2004.08.007","volume":"1703","author":"MJ Davies","year":"2005","unstructured":"Davies MJ (2005) The oxidative environment and protein damage. Biochim Biophys Acta 1703(2):93\u2013109","journal-title":"Biochim Biophys Acta"},{"issue":"9","key":"10302_CR27","doi-asserted-by":"publisher","first-page":"3117","DOI":"10.1002\/jps.21617","volume":"98","author":"P Qi","year":"2009","unstructured":"Qi P, Volkin DB, Zhao H, Nedved ML, Hughes R, Bass R, Yi SC, Panek ME, Wang D, Dalmonte P, Bond MD (2009) Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form. J Pharm Sci 98(9):3117\u20133130","journal-title":"J Pharm Sci"},{"issue":"4","key":"10302_CR28","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1007\/s11095-009-0045-6","volume":"27","author":"MC Manning","year":"2010","unstructured":"Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS (2010) Stability of protein pharmaceuticals: an update. Pharm Res 27(4):544\u2013575","journal-title":"Pharm Res"},{"issue":"6","key":"10302_CR29","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jps.20815","volume":"96","author":"BA Kerwin","year":"2007","unstructured":"Kerwin BA, Remmele RL Jr. (2007) Protect from light: photodegradation and protein biologics. J Pharm Sci 96(6):1468\u20131479","journal-title":"J Pharm Sci"},{"issue":"1","key":"10302_CR30","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1021\/js980221r","volume":"88","author":"BA Kerwin","year":"1999","unstructured":"Kerwin BA, Akers MJ, Apostol I, Moore-Einsel C, Etter JE, Hess E, Lippincott J, Levine J, Mathews AJ, Revilla-Sharp P, Schubert R, Looker DL (1999) Acute and long-term stability studies of deoxy hemoglobin and characterization of ascorbate-induced modifications. J Pharm Sci 88(1):79\u201388","journal-title":"J Pharm Sci"},{"issue":"8","key":"10302_CR31","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1021\/js9504550","volume":"85","author":"S Li","year":"1996","unstructured":"Li S, Patapoff TW, Nguyen TH, Borchardt RT (1996) Inhibitory effect of sugars and polyols on the metal-catalyzed oxidation of human relaxin. J Pharm Sci 85(8):868\u2013872","journal-title":"J Pharm Sci"},{"issue":"12","key":"10302_CR32","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1007\/s11095-004-7692-4","volume":"21","author":"J Yin","year":"2004","unstructured":"Yin J, Chu JW, Ricci MS, Brems DN, Wang DI, Trout BL (2004) Effects of antioxidants on the hydrogen peroxide-mediated oxidation of methionine residues in granulocyte colony-stimulating factor and human parathyroid hormone fragment 13\u201334. Pharm Res 21(12):2377\u20132383","journal-title":"Pharm Res"},{"issue":"11","key":"10302_CR33","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1021\/js970143s","volume":"86","author":"XM Lam","year":"1997","unstructured":"Lam XM, Yang JY, Cleland JL (1997) Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J Pharm Sci 86(11):1250\u20131255","journal-title":"J Pharm Sci"},{"issue":"2","key":"10302_CR34","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1081\/PDT-120030247","volume":"9","author":"J Hong","year":"2004","unstructured":"Hong J, Lee E, Carter JC, Masse JA, Oksanen DA (2004) Antioxidant-accelerated oxidative degradation: a case study of transition metal ion catalyzed oxidation in formulation. Pharm Dev Technol 9(2):171\u2013179","journal-title":"Pharm Dev Technol"},{"issue":"1\u20132","key":"10302_CR35","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.ijpharm.2004.01.006","volume":"273","author":"AB Joshi","year":"2004","unstructured":"Joshi AB, Kirsch LE (2004) The estimation of glutaminyl deamidation and aspartyl cleavage rates in glucagon. Int J Pharm 273(1\u20132):213\u2013219","journal-title":"Int J Pharm"},{"issue":"6","key":"10302_CR36","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1046\/j.1399-3011.2003.00089.x","volume":"62","author":"E Tarelli","year":"2003","unstructured":"Tarelli E, Corran PH (2003) Ammonia cleaves polypeptides at asparagine proline bonds. J Pept Res 62(6):245\u2013251","journal-title":"J Pept Res"},{"issue":"2","key":"10302_CR37","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.ab.2009.03.027","volume":"389","author":"D Ouellette","year":"2009","unstructured":"Ouellette D, Alessandri L, Piparia R, Aikhoje A, Chin A, Radziejewski C, Correia I (2009) Elevated cleavage of human immunoglobulin gamma molecules containing a lambda light chain mediated by iron and histidine. Anal Biochem 389(2):107\u2013117","journal-title":"Anal Biochem"},{"issue":"1","key":"10302_CR38","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/0003-2697(70)90345-3","volume":"36","author":"M Ledvina","year":"1970","unstructured":"Ledvina M, LaBella FS (1970) Fluorescent substances in protein hydrolyzates. I. Acid, \u201chydrolyzates\u201d of individual amino acids. Anal Biochem 36(1):174\u2013181","journal-title":"Anal Biochem"},{"key":"10302_CR39","doi-asserted-by":"crossref","unstructured":"Manning MC, Evans GJ, and Payne RW (2010) Protein stability during bioprocessing. Formul. Process Dev. Strateg. Manuf. Biopharm., John Wiley & Sons, Inc: 605\u2013624","DOI":"10.1002\/9780470595886.ch25"},{"issue":"3","key":"10302_CR40","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1080\/10837450701247350","volume":"12","author":"A Hawe","year":"2007","unstructured":"Hawe A, Friess W (2007) Formulation development for hydrophobic therapeutic proteins. Pharm Dev Technol 12(3):223\u2013237","journal-title":"Pharm Dev Technol"},{"issue":"4","key":"10302_CR41","doi-asserted-by":"publisher","first-page":"348","DOI":"10.2174\/138920109788488932","volume":"10","author":"JS Philo","year":"2009","unstructured":"Philo JS, Arakawa T (2009) Mechanisms of protein aggregation. Curr Pharm Biotechnol 10(4):348\u2013351","journal-title":"Curr Pharm Biotechnol"},{"issue":"3","key":"10302_CR42","doi-asserted-by":"publisher","first-page":"E572","DOI":"10.1208\/aapsj080366","volume":"8","author":"ME Cromwell","year":"2006","unstructured":"Cromwell ME, Hilario E, Jacobson F (2006) Protein aggregation and bioprocessing. AAPS J 8(3):E572\u2013E579","journal-title":"AAPS J"},{"issue":"1\u20132","key":"10302_CR43","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0168-3659(96)01353-3","volume":"41","author":"BJ Aungst","year":"1996","unstructured":"Aungst BJ, Saitoh H, Burcham DL, Huang SM, Mousa SA, Hussain MA (1996) Enhancement of the intestinal absorption of peptides and nonpeptides. J Controll Release 41(1\u20132):19\u201331","journal-title":"J Controll Release"},{"issue":"2\u20133","key":"10302_CR44","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S0169-409X(97)00045-8","volume":"27","author":"GM Pauletti","year":"1997","unstructured":"Pauletti GM, Gangwar S, Siahaan TJ, Aub\u00e9 J, Borchardt RT (1997) Improvement of oral peptide bioavailability: peptidomimetics and prodrug strategies. Advanced Drug Deliv Rev 27(2\u20133):235\u2013256","journal-title":"Advanced Drug Deliv Rev"},{"issue":"3","key":"10302_CR45","doi-asserted-by":"publisher","first-page":"207","DOI":"10.52711\/2231-5713.2023.00037","volume":"13","author":"SD Mankar","year":"2023","unstructured":"Mankar SD, Jadhav BS, Kale AN (2023) Basics and recent advances in peptide and protein drug delivery. Asian J Pharm Technol 13(3):207\u2013212","journal-title":"Asian J Pharm Technol"},{"issue":"9","key":"10302_CR46","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1002\/jps.20125","volume":"93","author":"L Tang","year":"2004","unstructured":"Tang L, Persky AM, Hochhaus G, Meibohm B (2004) Pharmacokinetic aspects of biotechnology products. J Pharm Sci 93(9):2184\u20132204","journal-title":"J Pharm Sci"},{"key":"10302_CR47","first-page":"96","volume":"20","author":"K Tryggvason","year":"2005","unstructured":"Tryggvason K, Wartiovaara J (2005) How does the kidney filter plasma? Physiology (Bethesda) 20:96\u2013101","journal-title":"Physiology (Bethesda)"},{"key":"10302_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-61779-921-1_1","volume":"899","author":"DS Dimitrov","year":"2012","unstructured":"Dimitrov DS (2012) Therapeutic proteins. Methods Mol Biol 899:1\u201326","journal-title":"Methods Mol Biol"},{"key":"10302_CR49","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S1387-2656(08)00007-0","volume":"14","author":"H Schellekens","year":"2008","unstructured":"Schellekens H (2008) How to predict and prevent the immunogenicity of therapeutic proteins. Biotechnol Annu Rev 14:191\u2013202","journal-title":"Biotechnol Annu Rev"},{"key":"10302_CR50","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S0065-3233(08)60656-7","volume":"51","author":"SN Timasheff","year":"1998","unstructured":"Timasheff SN (1998) Control of protein stability and reactions by weakly interacting cosolvents: the simplicity of the complicated. Adv Protein Chem 51:355\u2013432","journal-title":"Adv Protein Chem"},{"issue":"4","key":"10302_CR51","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.jab.2016.06.002","volume":"14","author":"B Khameneh","year":"2016","unstructured":"Khameneh B, Saberi MR, Hassanzadeh-Khayyat M, Mohammadpanah H, Ghandadi M, Iranshahi M, Baratian A, Jaafari MR (2016) Evaluation of physicochemical and stability properties of human growth hormone upon enzymatic PEGylation. J Appl Biomed 14(4):257\u2013264","journal-title":"J Appl Biomed"},{"key":"10302_CR52","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1007\/s11095-009-0045-6","volume":"27","author":"MC Manning","year":"2010","unstructured":"Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS (2010) Stability of protein pharmaceuticals: an update. Pharm Res 27:544\u2013575","journal-title":"Pharm Res"},{"issue":"6","key":"10302_CR53","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.addr.2012.10.007","volume":"65","author":"Y Yun","year":"2013","unstructured":"Yun Y, Cho YW, Park K (2013) Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliv Rev 65(6):822\u2013832","journal-title":"Adv Drug Deliv Rev"},{"issue":"16","key":"10302_CR54","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.4155\/fmc.14.125","volume":"6","author":"C Ginn","year":"2014","unstructured":"Ginn C, Khalili H, Lever R, Brocchini S (2014) PEGylation and its impact on the design of new protein-based medicines. Future Med Chem 6(16):1829\u20131846","journal-title":"Future Med Chem"},{"key":"10302_CR55","unstructured":"PEGylated Proteins Market Size to Hit Around US$ 4.9 Bn by 2032 2023; Available from: https:\/\/www.precedenceresearch.com\/pegylated-proteins-market"},{"key":"10302_CR56","unstructured":"Mordor Intelligence. PEGylated proteins market\u2013growth, trends, covid-19 impact, and forecasts (2023); Available from: https:\/\/www.mordorintelligence.com\/industry-reports\/"},{"key":"10302_CR57","unstructured":"American cancer society. Key statistics for prostate cancer (2022); Available from: https:\/\/www.cancer.org\/cancer\/prostate-cancer\/about\/key-statistics.html"},{"issue":"3","key":"10302_CR58","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nrd1033","volume":"2","author":"JM Harris","year":"2003","unstructured":"Harris JM, Chess RB (2003) Effect of PEGylation on pharmaceuticals. Nat Rev Drug Discov 2(3):214\u2013221","journal-title":"Nat Rev Drug Discov"},{"issue":"1\u20132","key":"10302_CR59","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.ijpharm.2017.01.040","volume":"519","author":"J Morgenstern","year":"2017","unstructured":"Morgenstern J, Baumann P, Brunner C, Hubbuch J (2017) Effect of PEG molecular weight and PEGylation degree on the physical stability of PEGylated lysozyme. Int J Pharm 519(1\u20132):408\u2013417","journal-title":"Int J Pharm"},{"issue":"6","key":"10302_CR60","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1124\/mol.111.074997","volume":"80","author":"D Narasimhan","year":"2011","unstructured":"Narasimhan D, Collins GT, Nance MR, Nichols J, Edwald E, Chan J, Ko MC, Woods JH, Tesmer JJ, Sunahara RK (2011) Subunit stabilization and polyethylene glycolation of cocaine esterase improves in vivo residence time. Mol Pharmacol 80(6):1056\u20131065","journal-title":"Mol Pharmacol"},{"issue":"2","key":"10302_CR61","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.jconrel.2011.10.037","volume":"161","author":"G Pasut","year":"2012","unstructured":"Pasut G, Veronese FM (2012) State of the art in PEGylation: the great versatility achieved after forty years of research. J Control Release 161(2):461\u2013472","journal-title":"J Control Release"},{"issue":"5","key":"10302_CR62","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/S1359-6446(03)02610-2","volume":"8","author":"SA Marshall","year":"2003","unstructured":"Marshall SA, Lazar GA, Chirino AJ, Desjarlais JR (2003) Rational design and engineering of therapeutic proteins. Drug Discov Today 8(5):212\u2013221","journal-title":"Drug Discov Today"},{"issue":"2","key":"10302_CR63","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1517\/14728210902907847","volume":"14","author":"JS Kang","year":"2009","unstructured":"Kang JS, Deluca PP, Lee KC (2009) Emerging PEGylated drugs. Expert Opin Emerg Drugs 14(2):363\u2013380","journal-title":"Expert Opin Emerg Drugs"},{"issue":"1","key":"10302_CR64","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/biot.200900218","volume":"5","author":"S Jevsevar","year":"2010","unstructured":"Jevsevar S, Kunstelj M, Porekar VG (2010) PEGylation of therapeutic proteins. Biotechnol J 5(1):113\u2013128","journal-title":"Biotechnol J"},{"issue":"1","key":"10302_CR65","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/S1046-5928(03)00055-X","volume":"30","author":"S Foser","year":"2003","unstructured":"Foser S, Schacher A, Weyer KA, Brugger D, Dietel E, Marti S, Schreitm\u00fcller T (2003) Isolation, structural characterization, and antiviral activity of positional isomers of monopegylated interferon alpha-2a (PEGASYS). Protein Expr Purif 30(1):78\u201387","journal-title":"Protein Expr Purif"},{"issue":"10","key":"10302_CR66","doi-asserted-by":"publisher","first-page":"25831","DOI":"10.3390\/ijms161025831","volume":"16","author":"JK Dozier","year":"2015","unstructured":"Dozier JK, Distefano MD (2015) Site-specific PEGylation of therapeutic proteins. Int J Mol Sci 16(10):25831\u201325864","journal-title":"Int J Mol Sci"},{"issue":"4","key":"10302_CR67","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/S0169-409X(02)00027-3","volume":"54","author":"YS Wang","year":"2002","unstructured":"Wang YS, Youngster S, Grace M, Bausch J, Bordens R, Wyss DF (2002) Structural and biological characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications. Adv Drug Deliv Rev 54(4):547\u2013570","journal-title":"Adv Drug Deliv Rev"},{"issue":"10","key":"10302_CR68","doi-asserted-by":"publisher","first-page":"4167","DOI":"10.1002\/jps.21278","volume":"97","author":"CS Fishburn","year":"2008","unstructured":"Fishburn CS (2008) The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics. J Pharm Sci 97(10):4167\u20134183","journal-title":"J Pharm Sci"},{"key":"10302_CR69","unstructured":"Robert C Thompson, Michael T Brewer, and Tadahiko Kohno, (2003) PEGylation reagents and compounds formed therewith. Google Patents"},{"issue":"2","key":"10302_CR70","doi-asserted-by":"publisher","first-page":"31","DOI":"10.15415\/jtmge.2013.42006","volume":"4","author":"A Brem","year":"2013","unstructured":"Brem A, Ivens B (2013) Do frugal and reverse innovation foster sustainability? introduction of a conceptual framework. J Technol Manag Grow Econ 4(2):31\u201350","journal-title":"J Technol Manag Grow Econ"},{"key":"10302_CR71","first-page":"95","volume":"I","author":"G Pasut","year":"2006","unstructured":"Pasut G, Veronese FM (2006) PEGylation of proteins as tailored chemistry for optimized bioconjugates. Polymer Ther I:95\u2013134","journal-title":"Polymer Ther"},{"issue":"7","key":"10302_CR72","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1177\/0192623315591171","volume":"43","author":"IA Ivens","year":"2015","unstructured":"Ivens IA, Achanzar W, Baumann A, Br\u00e4ndli-Baiocco A, Cavagnaro J, Dempster M, Depelchin BO, Rovira AR, Dill-Morton L, Lane JH, Reipert BM, Salcedo T, Schweighardt B, Tsuruda LS, Turecek PL, Sims J (2015) PEGylated biopharmaceuticals: current experience and considerations for nonclinical development. Toxicol Pathol 43(7):959\u2013983","journal-title":"Toxicol Pathol"},{"issue":"5","key":"10302_CR73","first-page":"590","volume":"8","author":"DE Szymkowski","year":"2005","unstructured":"Szymkowski DE (2005) Creating the next generation of protein therapeutics through rational drug design. Curr Opin Drug Discov And Dev 8(5):590","journal-title":"Curr Opin Drug Discov And Dev"},{"issue":"9","key":"10302_CR74","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1080\/17425247.2016.1182485","volume":"13","author":"AA D\u2019Souza","year":"2016","unstructured":"D\u2019Souza AA, Shegokar R (2016) Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications. Expert Opin Drug Deliv 13(9):1257\u20131275","journal-title":"Expert Opin Drug Deliv"},{"issue":"1","key":"10302_CR75","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.addr.2007.04.017","volume":"60","author":"DM Piedmonte","year":"2008","unstructured":"Piedmonte DM, Treuheit MJ (2008) Formulation of Neulasta (pegfilgrastim). Adv Drug Deliv Rev 60(1):50\u201358","journal-title":"Adv Drug Deliv Rev"},{"key":"10302_CR76","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13036-019-0166-3","volume":"13","author":"AM Saleh","year":"2019","unstructured":"Saleh AM, Wilding KM, Calve S, Bundy BC, Kinzer-Ursem TL (2019) Non-canonical amino acid labeling in proteomics and biotechnology. J Biol Eng 13:43","journal-title":"J Biol Eng"},{"issue":"7","key":"10302_CR77","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1021\/bc2006847","volume":"23","author":"B Unterweger","year":"2012","unstructured":"Unterweger B, Stoisser T, Leitgeb S, Birner-Gr\u00fcnberger R, Nidetzky B (2012) Engineering of Aerococcus viridans L-lactate oxidase for site-specific PEGylation: characterization and selective bioorthogonal modification of a S218C mutant. Bioconjug Chem 23(7):1406\u20131414","journal-title":"Bioconjug Chem"},{"issue":"11","key":"10302_CR78","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1021\/bc300265n","volume":"23","author":"TH Kim","year":"2012","unstructured":"Kim TH, Jiang HH, Lim SM, Youn YS, Choi KY, Lee S, Chen X, Byun Y, Lee KC (2012) Site-specific PEGylated Exendin-4 modified with a high molecular weight trimeric PEG reduces steric hindrance and increases type 2 antidiabetic therapeutic effects. Bioconjug Chem 23(11):2214\u20132220","journal-title":"Bioconjug Chem"},{"issue":"5","key":"10302_CR79","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1002\/jps.22401","volume":"100","author":"C Mueller","year":"2011","unstructured":"Mueller C, Capelle MA, Arvinte T, Seyrek E, Borchard G (2011) Noncovalent pegylation by dansyl-poly (ethylene glycol) s as a new means against aggregation of salmon calcitonin. J Pharm Sci 100(5):1648\u20131662","journal-title":"J Pharm Sci"},{"issue":"1","key":"10302_CR80","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/jps.10270","volume":"92","author":"H Lee","year":"2003","unstructured":"Lee H, Park TG (2003) A novel method for identifying PEGylation sites of protein using biotinylated PEG derivatives. J Pharm Sci 92(1):97\u2013103","journal-title":"J Pharm Sci"},{"issue":"11","key":"10302_CR81","doi-asserted-by":"publisher","first-page":"3880","DOI":"10.1021\/bm2007967","volume":"12","author":"S Khondee","year":"2011","unstructured":"Khondee S, Olsen CM, Zeng Y, Middaugh CR, Berkland C (2011) Noncovalent PEGylation by polyanion complexation as a means to stabilize keratinocyte growth factor-2 (KGF-2). Biomacromol 12(11):3880\u20133894","journal-title":"Biomacromol"},{"issue":"2","key":"10302_CR82","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/jps.24217","volume":"104","author":"T Kurinomaru","year":"2015","unstructured":"Kurinomaru T, Shiraki K (2015) Noncovalent PEGylation of L-asparaginase using PEGylated polyelectrolyte. J Pharm Sci 104(2):587\u2013592","journal-title":"J Pharm Sci"},{"issue":"5849","key":"10302_CR83","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1126\/science.1147241","volume":"318","author":"H Lee","year":"2007","unstructured":"Lee H, Dellatore SM, Miller WM, Messersmith PB (2007) Mussel-inspired surface chemistry for multifunctional coatings. Science 318(5849):426\u2013430","journal-title":"Science"},{"key":"10302_CR84","unstructured":"U.S. Food and drug administration, YORVIPATH (PALOPEGTERIPARATIDE), ASCENDIS PHARMA BONE company. (2024). New drug application (NDA): 216490. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/216490s000lbl.pdf"},{"key":"10302_CR85","unstructured":"U.S. Food and drug administration, IZERVAY (AVACINCAPTAD PEGOL SODIUM), ASTELLAS company. (2023). New drug application (NDA): 217225. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/217225s000lbl.pdf"},{"key":"10302_CR86","unstructured":"U.S. Food and drug administration, STIMUFEND (PEGFILGRASTIM-FPGK), FRESENIUS KABI USA company. (2022).Biologic license application (BLA): 761173. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761173Orig1s000correctedlbl.pdf"},{"key":"10302_CR87","unstructured":"U.S. Food and drug administration, SYFOVRE (PEGCETACOPLAN), APELLIS PHARMS company. (2023).New drug application (NDA): 217171. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/217171s000lbl.pdf"},{"key":"10302_CR88","unstructured":"U.S. Food and drug administration, FYLNETRA (PEGFILGRASTIM-PBBK), KASHIV BIOSCIENCES LLC company. (2022). Biologic license application (BLA): 761084. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761084s000lbl.pdf"},{"key":"10302_CR89","unstructured":"U.S. Food and drug administration, BESREMI (ROPEGINTERFERON ALFA-2B-NJFT), PHARMAESSENTIA CORP company. (2021). Biologic license application (BLA): 761166. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/761166s000lbl.pdf"},{"key":"10302_CR90","unstructured":"U.S. Food and drug administration, EMPAVELI (PEGCETACOPLAN), APELLIS PHARMS company. (2021). New drug application (NDA): 215014. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/215014s000lbl.pdf"},{"key":"10302_CR91","unstructured":"U.S. Food and drug administration, NYVEPRIA (PEGFILGRASTIM-APGF), HOSPIRA INC. (2020). Biologic license application (BLA): 761111. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/761111lbl.pdf"},{"key":"10302_CR92","unstructured":"U.S. Food and drug administration, ZIEXTENZO (PEGFILGRASTIM-BMEZ), SANDOZ INC. (2019). Biologic license application (BLA): 761045. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/761045lbl.pdf"},{"key":"10302_CR93","unstructured":"U.S. Food and drug administration, UDENYCA (PEGFILGRASTIM-CBQV), COHERUS BIOSCIENCES INC. (2018). Biologic license application (BLA): 761039. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/761039s000lbl.pdf"},{"key":"10302_CR94","unstructured":"U.S. Food and drug administration, PALYNZIQ (PEGVALIASE-PQPZ), BIOMARIN PHARM company. (2018). Biologic license application (BLA): 761079. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/761079s000lbl.pdf"},{"key":"10302_CR95","unstructured":"U.S. Food and drug administration, REVCOVI (ELAPEGADEMASE-LVLR), CHIESI USA INC. (2018). Biologic license application (BLA): 761092. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/761092s000lbl.pdf"},{"key":"10302_CR96","unstructured":"U.S. Food and drug administration, FULPHILA (PEGFILGRASTIM-JMDB), MYLAN GMBH company. (2018). Biologic license application (BLA): 761075. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/761075s000lbl.pdf"},{"key":"10302_CR97","unstructured":"U.S. Food and drug administration, ASPARLAS (CALASPARGASE PEGOL-MKNL), SERVIER PHARMA LLC company. (2018). Biologic license application (BLA): 761102. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/761102s000lbl.pdf"},{"key":"10302_CR98","unstructured":"U.S. Food and drug administration, OMONTYS (PEGINESATIDE ACETATE), TAKEDA PHARMS USA company. (2012). New drug application (NDA): 202799. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2012\/202799s000lbl.pdf"},{"key":"10302_CR99","unstructured":"U.S. Food and drug administration, PEGINTRON (PEGINTERFERON ALFA-2B), SCHERING company. (2001). Biologic license application (BLA): 103949. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2001\/pegsche011901LB.PDF"},{"key":"10302_CR100","unstructured":"U.S. Food and drug administration, KRYSTEXXA (PEGLOTICASE), HORIZON PHARMA. (2010). Biologic license application (BLA): 125293. http:\/\/accessdata.fda.gov\/drugsatfda_docs\/label\/2010\/125293s0000lbl.pdf"},{"key":"10302_CR101","unstructured":"U.S. Food and drug administration, CIMZIA (CERTOLIZUMAB PEGOL), UCB INC. (2008). Biologic license application (BLA): 125160. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2008\/125160s000lbl.pdf"},{"key":"10302_CR102","unstructured":"U.S. Food and drug administration, MACUGEN (PEGAPTANIB SODIUM), BAUSCH AND LOMB INC. (2004). New drug application (NDA): 021756. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2004\/021756lbl.pdf"},{"key":"10302_CR103","unstructured":"U.S. Food and drug administration, SOMAVERT (PEGVISOMANT), PHARMACIA company. (2003). Biologic license application (BLA): 021106. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2003\/21106_somavert_lbl.pdf"},{"key":"10302_CR104","unstructured":"U.S. Food and drug administration, PEGASYS (PEGINTERFERON ALFA-2A), Pharmaand GmbH company. (2002). Biologic license application (BLA): 103964. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2002\/pegihof101602LB.htm"},{"key":"10302_CR105","unstructured":"U.S. Food and drug administration, NEULASTA (PEGFILGRASTIM), AMGEN company. (2002). Biologic license application (BLA): 125031. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2002\/pegfamg013102LB.pdf"},{"key":"10302_CR106","unstructured":"U.S. Food and drug administration, ADAGEN (PEGADEMASE BOVINE), LEADIANT BIOSCI INC company. (1990). Biologic license application (BLA): 019818. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/019818s053lbl.pdf"},{"key":"10302_CR107","unstructured":"U.S. Food and drug administration, ELFABRIO (PEGUNIGALSIDASE ALFA-IWXJ), CHIESI FARMACEUTICI SPA company. (2023). Biologic license application (BLA): 761161. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761161s000lbl.pdf"},{"key":"10302_CR108","unstructured":"U.S. Food and drug administration, ROLVEDON (EFLAPEGRASTIM-XNST), SPECTRUM PHARMS company. (2022). Biologic license application (BLA): 761148. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761148Orig1s000Corrected_lbl.pdf"},{"key":"10302_CR109","unstructured":"U.S. Food and drug administration, SKYTROFA (LONAPEGSOMATROPIN-TCGD), ASCENDIS PHARMA ENCOCRINOLOGY DIV A\/S. (2021). Biologic license application (BLA): 761177. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/761177Orig1s000lbl.pdf"},{"key":"10302_CR110","unstructured":"U.S. Food and drug administration, PLEGRIDY (PEGINTERFERON BETA-1A), BIOGEN IDEC INC. (2014). Biologic license application (BLA): 125499. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/125499lbl.pdf"},{"key":"10302_CR111","unstructured":"U.S. Food and drug administration, MIRCERA (METHOXY POLYETHYLENE GLYCOL-EPOETIN BETA), HOFFMAN-LA ROCHE. (2007). Biologic license application (BLA): 125164. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2007\/125164lbl.pdf"},{"key":"10302_CR112","unstructured":"U.S. Food and drug administration, MOVANTIK (NALOXEGOL OXALATE), VALINOR Company. (2014). New drug application (NDA): 204760. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/204760s000lbl.pdf"},{"key":"10302_CR113","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/B978-0-444-64081-9.00005-X","volume-title":"Polymer-Protein Conjugates","author":"NE Elsadek","year":"2020","unstructured":"Elsadek NE, Lila ASA, Ishida T (2020) 5\u2013Immunological responses to PEGylated proteins: anti-PEG antibodies. In: Pasut G, Zalipsky S (eds) Polymer-Protein Conjugates. Elsevier, pp 103\u2013123"},{"issue":"3","key":"10302_CR114","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2013006475","volume":"30","author":"DJ Hines","year":"2013","unstructured":"Hines DJ, Kaplan DL (2013) Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights. Crit Rev Ther Drug Carrier Syst 30(3):257\u2013276","journal-title":"Crit Rev Ther Drug Carrier Syst"},{"issue":"1","key":"10302_CR115","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1208\/s12249-014-0198-4","volume":"16","author":"E Khodaverdi","year":"2015","unstructured":"Khodaverdi E, Heidari Z, Tabassi SA, Tafaghodi M, Alibolandi M, Tekie FS, Khameneh B, Hadizadeh F (2015) Injectable supramolecular hydrogel from insulin-loaded triblock PCL-PEG-PCL copolymer and gamma-cyclodextrin with sustained-release property. AAPS PharmSciTech 16(1):140\u2013149","journal-title":"AAPS PharmSciTech"},{"issue":"2","key":"10302_CR116","doi-asserted-by":"publisher","first-page":"174","DOI":"10.2174\/1567201817666200120120105","volume":"17","author":"E Khodaverdi","year":"2020","unstructured":"Khodaverdi E, Delroba K, Mohammadpour F, Khameneh B, Sajadi Tabassi SA, Tafaghodi M, Kamali H, Hadizadeh F (2020) In-vitro release evaluation of growth hormone from an injectable in-situ forming gel using PCL-PEG-PCL thermosensitive triblock. Curr Drug Deliv 17(2):174\u2013183","journal-title":"Curr Drug Deliv"},{"issue":"5","key":"10302_CR117","doi-asserted-by":"publisher","first-page":"e1600519","DOI":"10.1126\/sciadv.1600519","volume":"2","author":"MM Pakulska","year":"2016","unstructured":"Pakulska MM, Elliott Donaghue I, Obermeyer JM, Tuladhar A, McLaughlin CK, Shendruk TN, Shoichet MS (2016) Encapsulation-free controlled release: electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. Sci Adv 2(5):e1600519","journal-title":"Sci Adv"},{"key":"10302_CR118","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23051008","author":"MR Villegas","year":"2018","unstructured":"Villegas MR, Baeza A, Vallet-Reg\u00ed M (2018) Nanotechnological strategies for protein delivery. Molecules. https:\/\/doi.org\/10.3390\/molecules23051008","journal-title":"Molecules"},{"issue":"6","key":"10302_CR119","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1021\/bc050171z","volume":"16","author":"H Zhu","year":"2005","unstructured":"Zhu H, Srivastava R, Brown JQ, McShane MJ (2005) Combined physical and chemical immobilization of glucose oxidase in alginate microspheres improves stability of encapsulation and activity. Bioconjug Chem 16(6):1451\u20131458","journal-title":"Bioconjug Chem"},{"issue":"12","key":"10302_CR120","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1007\/s11095-007-9367-4","volume":"24","author":"B Sarmento","year":"2007","unstructured":"Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D (2007) Alginate\/chitosan nanoparticles are effective for oral insulin delivery. Pharm Res 24(12):2198\u20132206","journal-title":"Pharm Res"},{"key":"10302_CR121","unstructured":"Pharmaceutical factory medical research center. Global polymers drug delivery market. (2023); Available from: https:\/\/www.verifiedmarketreports.com\/product\/polymers-drug-delivery-market\/"},{"issue":"1","key":"10302_CR122","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40824-020-00190-7","volume":"24","author":"YK Sung","year":"2020","unstructured":"Sung YK, Kim SW (2020) Recent advances in polymeric drug delivery systems. Biomater Res 24(1):1\u201312","journal-title":"Biomater Res"},{"key":"10302_CR123","doi-asserted-by":"publisher","first-page":"114904","DOI":"10.1016\/j.addr.2023.114904","volume":"199","author":"M Shi","year":"2023","unstructured":"Shi M, McHugh KJ (2023) Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems. Adv Drug Deliv Rev 199:114904","journal-title":"Adv Drug Deliv Rev"},{"issue":"12","key":"10302_CR124","first-page":"307","volume":"7","author":"N Dan","year":"2020","unstructured":"Dan N, Samanta K, Almoazen H (2020) An update on pharmaceutical strategies for oral delivery of therapeutic peptides and proteins in adults and pediatrics. Children (Basel) 7(12):307","journal-title":"Children (Basel)"},{"issue":"6","key":"10302_CR125","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s40005-018-00422-y","volume":"49","author":"E Khodaverdi","year":"2019","unstructured":"Khodaverdi E, Maftouhian S, Aliabadi A, Hassanzadeh-Khayyat M, Mohammadpour F, Khameneh B, Hadizadeh F (2019) Casein-based hydrogel carrying insulin: preparation, in vitro evaluation and in vivo assessment. J Pharm Investig 49(6):635\u2013641","journal-title":"J Pharm Investig"},{"key":"10302_CR126","unstructured":"U.S. Food and drug administration, SUBLOCADE (BUPRENORPHINE) INDIVIOR company. (2017). New drug application (NDA): 209819. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/209819s000lbl.pdf"},{"key":"10302_CR127","unstructured":"U.S. Food and drug administration, ZILRETTA (TRIAMCINOLONE ACETONIDE) PACIRA PHARMS INC. (2017). New drug application (NDA): 208845. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/208845s000lbl.pdf"},{"key":"10302_CR128","unstructured":"U.S. Food and drug administration, GLIADEL (CARMUSTINE), AZURITY company. (1996). New drug application (NDA): 020637. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/96\/020637Orig1s000.pdf"},{"key":"10302_CR129","unstructured":"U.S. Food and drug administration, ELIGARD (LEUPROLIDE ACETATE), TOLMAR company. (2002). New drug application (NDA): 021343. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2002\/21343lbl.pdf"},{"key":"10302_CR130","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.actbio.2023.06.005","volume":"167","author":"F Veider","year":"2023","unstructured":"Veider F, Knoll P, J\u00f6rgensen AM, Stengel D, Bernkop-Schn\u00fcrch A (2023) Oral drug delivery: influence of mucus on cellular interactions and uptake of lipid-based nanocarriers in Caco-2 cells. Acta Biomater 167:416\u2013424","journal-title":"Acta Biomater"},{"key":"10302_CR131","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.jcis.2020.12.019","volume":"587","author":"NN Le","year":"2021","unstructured":"Le NN, Steinbring C, Le-Vinh B, Jalil A, Matuszczak B, Bernkop-Schn\u00fcrch A (2021) Polyphosphate coatings: a promising strategy to overcome the polycation dilemma. J Colloid Interface Sci 587:279\u2013289","journal-title":"J Colloid Interface Sci"},{"key":"10302_CR132","unstructured":"U.S. Food and drug administration, BRIXADI (BUPRENORPHINE), BRAEBURN company. (2023). New drug application (NDA): 210136. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/210136Orig1s000lbl.pdf"},{"key":"10302_CR133","unstructured":"U.S. Food and drug administration, DIPRIVAN (PROPOFOL), FRESENIUS KABI USA Company. 91989). New drug application (NDA): 019627. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/019627s069lbl.pdf"},{"key":"10302_CR134","unstructured":"U.S. Food and drug administration, CINVANTI (APREPITANT), HERON THERAPS INC. (2017). New drug application (NDA): 209296. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/209296s000lbl.pdf"},{"key":"10302_CR135","unstructured":"U.S. Food and drug administration, DOXIL LIPOSOMAL (DOXORUBICIN HYDROCHLORIDE), BAXTER HLTHCARE CORP company (1995). New drug application (NDA): 050718. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/050718Orig1s060lbl.pdf"},{"key":"10302_CR136","unstructured":"U.S. Food and drug administration, DAUNOXOME (DAUNORUBICIN CITRATE), GALEN (UK) company. (1996). New drug application (NDA): 050704. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/appletter\/2002\/50704s8ltr.pdf"},{"key":"10302_CR137","unstructured":"U.S. Food and drug administration, ONIVYDE (IRINOTECAN HYDROCHLORIDE), IPSEN Company. (2015). New drug application (NDA): 207793. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/207793lbl.pdf"},{"key":"10302_CR138","unstructured":"U.S. Food and drug administration, AMBISOME (AMPHOTERICIN B), ASTELLAS Company. (1997). New drug application (NDA): 050740. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/050740Orig1s037Lbl.pdf"},{"key":"10302_CR139","unstructured":"U.S. Food and drug administration, VISUDYNE (VERTEPORFIN), BAUSCH LOMB IRELAND Company. (2000). New drug application (NDA): 021119. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/021119s034lbl.pdf"},{"key":"10302_CR140","unstructured":"U.S. Food and drug administration, ONPATTRO (PATISIRAN SODIUM), ALNYLAM PHARMS INC. (2018). New drug application (NDA): 210922. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/210922s012lbl.pdf"}],"container-title":["The Protein Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10930-025-10302-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10930-025-10302-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10930-025-10302-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:25:28Z","timestamp":1772551528000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10930-025-10302-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,8]]},"references-count":140,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["10302"],"URL":"https:\/\/doi.org\/10.1007\/s10930-025-10302-8","relation":{},"ISSN":["1875-8355"],"issn-type":[{"value":"1875-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,8]]},"assertion":[{"value":"2 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}