{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:13:20Z","timestamp":1788322400001,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMR-1727015"],"award-info":[{"award-number":["DMR-1727015"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1919722"],"award-info":[{"award-number":["1919722"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R25GM054939"],"award-info":[{"award-number":["5R25GM054939"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>A self-assembled co-hydrogel system with sol-gel two-phase coexistence and mucoadhesive properties was developed based on the combined properties of fluoroalkyl double-ended poly(ethylene glycol) (Rf-PEG-Rf) and poly(acrylic acid) (PAA), respectively. We have synthesized an Rf-PEG-g-PAA (where g denotes grafted) copolymer and integrated it into the Rf-PEG-Rf physically cross-linked micellar network to form a co-hydrogel system. Tensile strengths between the co-hydrogel surfaces and two different sets of mucosal surfaces were acquired. One mucosal surface was made of porcine stomach mucin Type II, while the other one is a pig small intestine. The experimental results show that the largest maximum detachment stresses (MDSs) were obtained when the Rf-PEG-g-PAA\u2019s weight percent in the dehydrated polymer mixture is ~15%. Tensile experiments also found that MDSs are greater in acidic conditions (pH = 4\u20135) (123.3 g\/cm2 for the artificial mucus, and 43.0 g\/cm2 for pig small intestine) and basic conditions (pH = 10.6) (126.9 g\/cm2, and 44.6 g.cm2, respectively) than in neutral pH (45.4 g\/cm2, and 30.7 g.cm2, respectively). Results of the rheological analyses using shear strain amplitude sweep and frequency sweep reveal that the Rf-PEG-g-PAA was physically integrated into the Rf-PEG-Rf micellar network, and the co-hydrogels remain physically cross-linked in three-dimensional micellar networks with long-term physical dispersion stability. Therefore, the co-hydrogel system is promising for drug delivery applications on mucosal surfaces.<\/jats:p>","DOI":"10.3390\/polym13121956","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T22:25:46Z","timestamp":1623709546000},"page":"1956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mucoadhesive and Rheological Studies on the Co-Hydrogel Systems of Poly(Ethylene Glycol) Copolymers with Fluoroalkyl and Poly(Acrylic Acid)"],"prefix":"10.3390","volume":"13","author":[{"given":"Yang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, Los Angeles, CA 90032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4916-5645","authenticated-orcid":false,"given":"Adiel F.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, Los Angeles, CA 90032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8456-1918","authenticated-orcid":false,"given":"Ivy L.","family":"Cardoza","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, Los Angeles, CA 90032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Baluyot-Reyes","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, Los Angeles, CA 90032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ba","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, Los Angeles, CA 90032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wise, D.L., Brannon-Peppas, L., Klibanov, A.M., Langer, R.L., Mikos, A.G., Peppas, N.A., Trantolo, D.J., Wnek, G.E., and Yaszemski, M.J. (2000). Bioadhesive controlled release systems. Handbook of Pharmaceutical Controlled Release Technology, Dekker.","DOI":"10.1201\/9781482289985-42"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/1520-6017(200007)89:7<850::AID-JPS2>3.0.CO;2-G","article-title":"Bioadhesive-based dosage forms: The next generation","volume":"89","author":"Robinson","year":"2000","journal-title":"J. Pharm. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0939-6411(00)00090-4","article-title":"Hydrogels in pharmaceutical formulations","volume":"50","author":"Peppas","year":"2000","journal-title":"Eur J. Pharm. Biopharm."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Harris, J.M. (1992). Ploy(ethylene glycol) Chemistry. Biotechnical and Biomedical Applications, Plenum Press.","DOI":"10.1007\/978-1-4899-0703-5"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1021\/bc00032a002","article-title":"Functionalized Poly(ethylene glycol) for Preparation of Biologically Relevant Conjugates","volume":"6","author":"Zalipsky","year":"1995","journal-title":"Bioconjugate Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/bjc.1996.99","article-title":"Polyethylene glycol modification of a galactosylated streptavidin clearing agent: Effects on immunogenicity and clearance of a biotinylated anti-tumour antibody","volume":"73","author":"Marshall","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nrd1033","article-title":"Effect of pegylation on pharmaceuticals","volume":"2","author":"Harris","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5084","DOI":"10.1021\/acs.macromol.6b01085","article-title":"Precision Self-Assembly of Amphiphilic Random Copolymers into Uniform and Self-Sorting Nanocompartments in Water","volume":"49","author":"Hirai","year":"2016","journal-title":"Macromolecules"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0168-3659(85)90032-X","article-title":"Physico-chemical properties of water insoluble polymers important to mucin\/epithelial adhesion","volume":"2","author":"Park","year":"1985","journal-title":"J. Control Release"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1023\/A:1016467219657","article-title":"Mechanisms of mucoadhesion of poly(acrylic acid) hydrogels","volume":"4","author":"Park","year":"1987","journal-title":"Pharm. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/jps.2600740407","article-title":"Bioadhesive polymers as platforms for oral controlled drug delivery. II. Synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers","volume":"74","author":"Park","year":"1985","journal-title":"J. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1081\/DDC-100101318","article-title":"Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: A review","volume":"26","author":"Singla","year":"2000","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3109\/03639049709148498","article-title":"Mucoadhesive drug delivery systems","volume":"23","author":"Ahuja","year":"1997","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejpb.2005.10.011","article-title":"Design of poly(ethylene glycol)-tethered copolymers as novel mucoadhesive drug delivery systems","volume":"63","author":"Serra","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.ijbiomac.2018.11.252","article-title":"pH-Thermosensitive hydrogel based on polyvinyl alcohol\/sodium alginate\/N-isopropyl acrylamide composite for treating re-infected wounds","volume":"124","author":"Montaser","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","unstructured":"(1981). Structure and Function of Gastrointestinal Mucus, Raven Press. [1st ed.]. Allen, A., Ed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1021\/bm025767t","article-title":"The gel matrix of gastric mucus is maintained by a complex interplay of transient and nontransient associations","volume":"4","author":"Taylor","year":"2003","journal-title":"Biomacromolecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.ijbiomac.2019.04.065","article-title":"Wound dressing properties of cationized cotton fabric treated with carrageenan\/cyclodextrin hydrogel loaded with honey bee propolis extract","volume":"133","author":"Sharaf","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1021\/acs.macromol.9b02595","article-title":"Blended Assemblies of Amphiphilic Random and Block Copolymers for Tunable Encapsulation and Release of Hydrophobic Guest Molecules","volume":"53","author":"Jiang","year":"2020","journal-title":"Macromolecules"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1039\/b925218p","article-title":"Hydrogel nanocomposites: A review of applications as remote controlled biomaterials","volume":"6","author":"Satarkar","year":"2021","journal-title":"Soft Matter"},{"key":"ref_21","first-page":"112","article-title":"Preparation methods and properties of hydrogel: A review","volume":"5","author":"Das","year":"2013","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.jsps.2015.03.022","article-title":"Methods of synthesis of hydrogels \u2026 A review","volume":"24","author":"Akhtar","year":"2016","journal-title":"Saudi Pharm. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1021\/ma0107511","article-title":"Hydrogels with Controlled, Surface Erosion Characteristics from Self-Assembly of Fluoroalkyl-Ended Poly(ethylene glycol)","volume":"34","author":"Tae","year":"2001","journal-title":"Macromolecules"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1021\/ma011809e","article-title":"Ordering Transitions of Fluoroalkyl-Ended Poly(ethylene glycol): Rheology and SANS","volume":"35","author":"Tae","year":"2002","journal-title":"Macromolecules"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5259","DOI":"10.1016\/j.biomaterials.2005.01.042","article-title":"Sustained release of human growth hormone from in situ forming hydrogels using self-assembly of fluoroalkyl-ended poly(ethylene glycol)","volume":"26","author":"Taea","year":"2005","journal-title":"Biomaterials"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0168-3659(85)90050-1","article-title":"Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues","volume":"2","author":"Peppas","year":"1985","journal-title":"J. Control Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/actp.1983.010340210","article-title":"Adhesion between polymers","volume":"34","author":"Kammer","year":"1983","journal-title":"Acta Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0168-3659(87)90004-6","article-title":"Bioadhesive analysis of controlled release systems. I. Fracture and interpenetration analysis in poly(acrylic acid)-containing systems","volume":"5","author":"Ponchel","year":"1987","journal-title":"J. Control Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1021\/bm990017d","article-title":"Structural and Rheological Properties of Methacrylamide Modified Gelatin Hydrogels","volume":"1","author":"Bulcke","year":"2000","journal-title":"Biomacromolecules"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1021\/bm700762w","article-title":"Rheological Study of Genipin Cross-Linked Chitosan Hydrogels","volume":"8","author":"Moura","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.foodhyd.2018.09.040","article-title":"On relating rheology and oral tribology to sensory properties in hydrogels","volume":"88","author":"Krop","year":"2019","journal-title":"Food Hydrocoll."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.lwt.2015.03.024","article-title":"The rheology of gelatin hydrogels modified by k-carrageenan","volume":"63","author":"Derkach","year":"2015","journal-title":"LWT\u2013Food Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.carbpol.2017.03.068","article-title":"Rheology of Laponite-scleroglucan hydrogels","volume":"168","author":"Lapasin","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1039\/c0sm00573h","article-title":"Cosolvent-regulated time\u2013composition rheological equivalence in block copolymer solutions","volume":"6","author":"Krishnan","year":"2010","journal-title":"Soft Matter"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1021\/ma502111p","article-title":"Rheology of Poly(N-isopropylacrylamide)\u2212Clay Nanocomposite Hydrogels","volume":"48","author":"Gersappe","year":"2015","journal-title":"Macromolecules"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10971-007-1659-y","article-title":"Study the property of double-ended fluoroalkyl poly(ethylene glycol) hydrogel as a depot for hydrophobic drug delivery using electron paramagnetic resonance technique and cell proliferation assay","volume":"45","author":"Liu","year":"2008","journal-title":"J. Sol-Gel. Sci. Techn."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1021\/la701833w","article-title":"A Model of Drug-Loaded Fluorocarbon-based Micelles Studied by Electron-Spin Induced 19F Relaxation NMR and Molecular Dynamics Modeling","volume":"24","author":"Mathias","year":"2008","journal-title":"Langmuir"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1007\/s00396-010-2304-9","article-title":"Properties of Small Molecular Drug Loading and Diffusion in a Fluorinated PEG Hydrogel Studied by 1H Diffuion NMR and 19F Spin Diffusion NMR","volume":"288","author":"Mathias","year":"2010","journal-title":"Colloid Polym. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1021\/la960799l","article-title":"Synthesis, Characterization, and Rheological Behavior of Polyethylene Glycols End-Capped with Fluorocarbon Hydrophobes","volume":"13","author":"Xu","year":"1997","journal-title":"Langmuir"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1193A","DOI":"10.1021\/ac00024a716","article-title":"Matrix-assisted laser desorption\/ionization mass spectrometry of biopolymers","volume":"63","author":"Hillenkamp","year":"1991","journal-title":"Anal. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1021\/ma100599n","article-title":"MALDI-TOF Mass Spectral Characterization of Polymers Containing an Azide Group: Evidence of Metastable Ions","volume":"43","author":"Li","year":"2010","journal-title":"Macromolecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.colsurfb.2011.12.020","article-title":"Comparison of in vitro methods of measuring mucoadhesion: Ellipsometry, tensile strength and rheological measurements","volume":"92","author":"Ivarsson","year":"2012","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ijpharm.2004.05.030","article-title":"Bioadhesive properties and rheology of polyether-modified poly(acrylic acid) hydrogels","volume":"282","author":"Bromberg","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/nature04162","article-title":"Interfaces and the driving force of hydrophobic assembly","volume":"437","author":"Chandler","year":"2005","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s12154-013-0094-5","article-title":"Fluorescent labeling and modification of proteins","volume":"6","author":"Toseland","year":"2013","journal-title":"J. Chem. Biol."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/13\/12\/1956\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:13:37Z","timestamp":1760163217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/13\/12\/1956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,12]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["polym13121956"],"URL":"https:\/\/doi.org\/10.3390\/polym13121956","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,12]]}}}