{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:25:17Z","timestamp":1786465517778,"version":"build-2736575974"},"reference-count":30,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001797","name":"Pharmaceutical Research and Manufacturers of America Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016204","name":"Ministry of Higher Education, Science, Research and Innovation, Thailand","doi-asserted-by":"publisher","award":["50DE004"],"award-info":[{"award-number":["50DE004"]}],"id":[{"id":"10.13039\/501100016204","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Curcumin exhibits antimicrobial activity against Gram-negative bacteria but is limited by rapid hydrolytic degradation at near-neutral pH. We hypothesized that chitosan, a cationic polymer that independently destabilizes the Gram-negative outer membrane, could simultaneously stabilize curcumin and potentiate its antibacterial activity. Curcumin degradation kinetics in cation-adjusted Mueller\u2013Hinton broth (35\u201385 \u00b0C) revealed a concentration-dependent transition in chitosan-mediated stabilization: low chitosan ratios (1:0.5\u20131:1) reduced degradation rates without altering activation energy (\u223c33\u201335 kJ\/mol), consistent with kinetic shielding, whereas higher ratios (1:2\u20131:3) increased activation energy to 39.0\u201345.8 kJ\/mol, indicating formation of a protective curcumin\u2013chitosan complex. Complementary microplate kinetic spectroscopy at 35 \u00b0C across pH 6.6, 7.2, and 7.4 confirmed that chitosan-mediated stabilization is itself pH-dependent, extending curcumin\u2019s half-life by up to 10.8-fold at pH 7.2 (1:2 ratio) and 5.9-fold at pH 6.6 (1:3 ratio). Checkerboard synergy assays against six Pseudomonas aeruginosa isolates revealed pH-dependent potentiation consistent with synergy (Bliss Independence model), with mean Bliss \u0394 shifting from +0.112 at pH 6.6 to \u22120.019 at pH 7.4, tracking the ionization of chitosan\u2019s amine groups (pKa 6.2\u20136.5). At a 24-h end point, the 1:2 combination produced greater nucleic acid and protein leakage than either agent alone; however, a complementary short-duration kinetic assay (0\u2013120 min) across three pH values indicated that this enhancement reflects chitosan-mediated stabilization extending curcumin\u2019s effective exposure duration rather than direct mechanistic synergy at the membrane. Together, these results identify a composite mechanism in which chitosan protects curcumin from hydrolysis while both agents contribute pH-dependent membrane disruption, with maximal antibacterial potentiation in the pH range characteristic of the cystic fibrosis airway.<\/jats:p>","DOI":"10.1021\/acsomega.6c02415","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:10:15Z","timestamp":1785849015000},"page":"46088-46104","source":"Crossref","is-referenced-by-count":0,"title":["Chitosan Stabilizes\nCurcumin against Hydrolysis and\nPotentiates Antimicrobial Activity against\n                    <i>Pseudomonas aeruginosa<\/i>\n                    in a pH-Dependent Manner"],"prefix":"10.1021","volume":"11","author":[{"given":"Bhanuz","family":"Dechayont","sequence":"first","affiliation":[{"name":"University of Michigan , , 1007 E. Huron St , , ,","place":["Ann Arbor, Michigan, United States, 48104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-5427","authenticated-orcid":true,"given":"Ashlee D.","family":"Brunaugh","sequence":"additional","affiliation":[{"name":"University of Michigan , , 1007 E. Huron St , , ,","place":["Ann Arbor, Michigan, United States, 48104"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"4","key":"2026081110184362500_cit1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1128\/MMBR.67.4.593-656.2003","article-title":"Molecular\nBasis of Bacterial Outer Membrane Permeability Revisited","volume":"67","author":"Nikaido","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"issue":"2","key":"2026081110184362500_cit2","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1017\/S0033583500001797","article-title":"Phase transitions\nand fluidity characteristics of lipids and cell membranes","volume":"8","author":"Chapman","year":"1975","journal-title":"Q. Rev. Biophys."},{"issue":"1","key":"2026081110184362500_cit3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/S0163-7827(01)00020-0","article-title":"Cholesterol interactions\nwith phospholipids in membranes","volume":"41","author":"Ohvo-Rekila\u0308","year":"2002","journal-title":"Prog. Lipid\nRes."},{"issue":"36","key":"2026081110184362500_cit4","doi-asserted-by":"publisher","first-page":"10384","DOI":"10.1021\/bi701013n","article-title":"Curcumin\nis a modulator of bilayer\nmaterial properties","volume":"46","author":"Ingolfsson","year":"2007","journal-title":"Biochemistry"},{"issue":"8","key":"2026081110184362500_cit5","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1021\/acs.jpcb.7b10566","article-title":"Characterization\nof Interactions between Curcumin and Different Types of Lipid Bilayers\nby Molecular Dynamics Simulation","volume":"122","author":"Lyu","year":"2018","journal-title":"J. Phys. Chem.\nB"},{"issue":"5","key":"2026081110184362500_cit6","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1021\/jf104402t","article-title":"Curcumin Nanoparticles:\nPreparation,\nCharacterization, and Antimicrobial Study","volume":"59","author":"Bhawana","year":"2011","journal-title":"J.\nAgric. Food Chem."},{"issue":"2","key":"2026081110184362500_cit7","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1177\/0748233713498458","article-title":"Antibacterial effects\nof curcumin: An in vitro minimum\ninhibitory concentration study","volume":"32","author":"Gunes","year":"2016","journal-title":"Toxicol. Ind.\nHealth"},{"issue":"41","key":"2026081110184362500_cit8","doi-asserted-by":"publisher","first-page":"9677","DOI":"10.1021\/ja991446m","article-title":"H-Atom\nTransfer\nIs A Preferred Antioxidant Mechanism of Curcumin","volume":"121","author":"Jovanovic","year":"1999","journal-title":"J. Am. Chem. Soc."},{"issue":"105","key":"2026081110184362500_cit9","doi-asserted-by":"publisher","first-page":"103275","DOI":"10.1039\/C6RA24256A","article-title":"Effect of pH and temperature\non conformational equilibria and aggregation\nbehaviour of curcumin in aqueous binary mixtures of ethanol","volume":"6","author":"Bhatia","year":"2016","journal-title":"RSC Adv."},{"issue":"18","key":"2026081110184362500_cit10","doi-asserted-by":"publisher","DOI":"10.1063\/1.4895539","article-title":"Hydrophobic\nhydration driven self-assembly of curcumin\nin water: Similarities to nucleation and growth under large metastability,\nand an analysis of water dynamics at heterogeneous surfaces","volume":"141","author":"Hazra","year":"2014","journal-title":"J. Chem. Phys."},{"issue":"5","key":"2026081110184362500_cit11","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/S1386-1425(03)00342-1","article-title":"Determination\nof acidity constants of curcumin in aqueous solution and apparent\nrate constant of its decomposition","volume":"60","author":"Bernabe\u0301-Pineda","year":"2004","journal-title":"Spectrochim.\nActa, Part A"},{"issue":"12","key":"2026081110184362500_cit12","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1016\/S0731-7085(96)02024-9","article-title":"Stability of curcumin in buffer solutions\nand characterization of its degradation products","volume":"15","author":"Wang","year":"1997","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"3","key":"2026081110184362500_cit13","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1039\/C6FO01770C","article-title":"Potential roles of\nchemical degradation in the biological activities of curcumin","volume":"8","author":"Zhu","year":"2017","journal-title":"Food Funct."},{"issue":"11","key":"2026081110184362500_cit14","doi-asserted-by":"publisher","first-page":"5672","DOI":"10.1021\/la800780w","article-title":"Encapsulation of Curcumin in Cationic\nMicelles Suppresses Alkaline Hydrolysis","volume":"24","author":"Leung","year":"2008","journal-title":"Langmuir"},{"issue":"10","key":"2026081110184362500_cit15","doi-asserted-by":"publisher","first-page":"5773","DOI":"10.1021\/la804215v","article-title":"Effective\nStabilization of Curcumin by Association\nto Plasma Proteins: Human Serum Albumin and Fibrinogen","volume":"25","author":"Leung","year":"2009","journal-title":"Langmuir"},{"issue":"22","key":"2026081110184362500_cit16","doi-asserted-by":"publisher","first-page":"23082","DOI":"10.1021\/acsomega.5c01178","article-title":"Stability\nof Curcumin on Amphiphilic Chitosan","volume":"10","author":"Poli","year":"2025","journal-title":"ACS Omega"},{"issue":"1","key":"2026081110184362500_cit17","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.tca.2004.03.012","article-title":"A thermodynamic investigation on chitosan\u2013divalent\ncation interactions","volume":"421","author":"Lima","year":"2004","journal-title":"Thermochim. 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U.S.A."},{"issue":"5","key":"2026081110184362500_cit21","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1562\/0031-8655(2000)0720625EOSOTE2.0.CO2","article-title":"Effect of\nSolvent on the Excited-state Photophysical Properties of Curcumin","volume":"72","author":"Khopde","year":"2000","journal-title":"Photochem. Photobiol."},{"key":"2026081110184362500_cit22","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jphotochemrev.2009.05.001","article-title":"Photophysics,\nphotochemistry and photobiology of curcumin: Studies from organic\nsolutions, bio-mimetics and living cells","volume":"10","author":"Priyadarsini","year":"2009","journal-title":"J.\nPhotochem. 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Chemother."},{"issue":"3","key":"2026081110184362500_cit25","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1021\/bm015531","article-title":"Relation between the\ndegree of acetylation and the electrostatic properties of chitin and\nchitosan","volume":"2","author":"Sorlier","year":"2001","journal-title":"Biomacromolecules"},{"issue":"5","key":"2026081110184362500_cit26","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1128\/JCM.42.5.1915-1922.2004","article-title":"Clinically feasible\nbiofilm susceptibility assay for isolates of Pseudomonas aeruginosa\nfrom patients with cystic fibrosis","volume":"42","author":"Moskowitz","year":"2004","journal-title":"J. Clin.\nMicrobiol."},{"issue":"5444","key":"2026081110184362500_cit27","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1126\/science.286.5444.1561","article-title":"Specific\nlipopolysaccharide found\nin cystic fibrosis airway Pseudomonas aeruginosa","volume":"286","author":"Ernst","year":"1999","journal-title":"Science"},{"issue":"1","key":"2026081110184362500_cit28","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-025-01031-w","article-title":"Curcumin-loaded chitosan nanoparticles: a promising\napproach to liver fibrosis prevention","volume":"26","author":"Hasanzade","year":"2025","journal-title":"BMC Pharmacol.\nToxicol."},{"issue":"6272","key":"2026081110184362500_cit29","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1126\/science.aad5589","article-title":"Airway acidification\ninitiates host defense\nabnormalities in cystic fibrosis mice","volume":"351","author":"Shah","year":"2016","journal-title":"Science"},{"issue":"3","key":"2026081110184362500_cit30","doi-asserted-by":"publisher","DOI":"10.3390\/polym10030267","article-title":"Chitosan\nand Its Derivatives for Application in Mucoadhesive Drug Delivery\nSystems","volume":"10","author":"M Ways","year":"2018","journal-title":"Polymers"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c02415","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/31\/46088\/66287340\/acsomega.6c02415.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/31\/46088\/66287340\/acsomega.6c02415.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:01:50Z","timestamp":1786460510000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/31\/46088\/5234385\/Chitosan-Stabilizes-Curcumin-against-Hydrolysis"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":30,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2026,7,27]]},"published-print":{"date-parts":[[2026,8,11]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c02415","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}