{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:39:43Z","timestamp":1785577183403,"version":"3.56.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"US Department of Agriculture","doi-asserted-by":"crossref","award":["2021-67015-35675"],"award-info":[{"award-number":["2021-67015-35675"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007756","name":"University of Arkansas","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007756","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Programa de Apoyo Institucional Para la Formaci\u00f3n en Estudios de Posgrados en Maestr\u00edas y Doctorados de La Universidad del Atl\u00e1ntico, Colombia"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of the microneedle patch. Results regarding the physical characteristics, chemical composition, and mechanical properties confirmed that rheological properties of the chitosan solution, present significant differences over time, demonstrating that reusing the solution on the fourth day results in failure patches. Morphological characteristics and chemical composition studies revealed that the process of sterilization (ethylene oxide gas) needed for implanting the patches into the skin did not affect the properties of microneedle patches. In-vitro studies showed that approximately 33.02 \u00b1 3.88% of the meloxicam was released over 7 days. A full penetration of the microneedles into the skin can be obtained by applying approximately 3.2 N. In-vivo studies demonstrated that microneedle patches were capable of swelling and dissolving, exhibiting a dissolution percentage of more than 50% of the original height of microneedle after 7 days. No abnormal tissue, swelling, or inflammation was observed in the implanted area. The results of this work show that chitosan biodegradable microneedle patches may be useful to deliver meloxicam to improve pain management of cattle with positive effects for commercial manufacturing.<\/jats:p>","DOI":"10.1371\/journal.pone.0272169","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T19:01:26Z","timestamp":1659466886000},"page":"e0272169","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Biodegradable microneedle patch for delivery of meloxicam for managing pain in cattle"],"prefix":"10.1371","volume":"17","author":[{"given":"David A.","family":"Castilla-Casadiego","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Miranda-Mun\u0303oz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse L.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7035-1100","authenticated-orcid":true,"given":"Anne D.","family":"Crowell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-6888","authenticated-orcid":true,"given":"David","family":"Gonzalez-Nino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipankar","family":"Choudhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank O.","family":"Aparicio-Solis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3075-5423","authenticated-orcid":true,"given":"Shannon L.","family":"Servoss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianne M.","family":"Rosales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-3214","authenticated-orcid":true,"given":"Gary","family":"Prinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuntao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann F.","family":"Coetzee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren F.","family":"Greenlee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-3878","authenticated-orcid":true,"given":"Jorge","family":"Almodovar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"pone.0272169.ref001","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.applanim.2015.08.023","article-title":"Pain evaluation in dairy cattle","volume":"171","author":"K.B. Gleerup","year":"2015","journal-title":"Applied Animal Behaviour Science"},{"key":"pone.0272169.ref002","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1136\/vr.159.20.662","article-title":"Current attitudes of cattle practitioners to pain and the use of analgesics in cattle","volume":"159","author":"J.N. Huxley","year":"2006","journal-title":"Veterinary Record"},{"key":"pone.0272169.ref003","doi-asserted-by":"crossref","first-page":"755","DOI":"10.2460\/javma.238.6.755","article-title":"Analgesic drug administration and attitudes about analgesia in cattle among bovine practitioners in the United States","volume":"238","author":"V.R. Fajt","year":"2011","journal-title":"J Am Vet Med Assoc"},{"key":"pone.0272169.ref004","doi-asserted-by":"crossref","first-page":"77","DOI":"10.15232\/aas.2020-02106","article-title":"INVITED REVIEW: On-farm pain management of food production animals","volume":"37","author":"M.D. Kleinhenz","year":"2021","journal-title":"Applied Animal Science"},{"key":"pone.0272169.ref005","first-page":"47","article-title":"Behavioral responses of cattle to pain and implications for diagnosis, management, and animal welfare","volume":"29","author":"S.T. Millman","year":"2013","journal-title":"Veterinary Clinics: Food Animal Practice"},{"key":"pone.0272169.ref006","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.cvfa.2017.02.009","article-title":"An Update on the Assessment and Management of Pain Associated with Lameness in Cattle","volume":"33","author":"J.F. Coetzee","year":"2017","journal-title":"Veterinary Clinics of North America\u2014Food Animal Practice"},{"key":"pone.0272169.ref007","unstructured":"American Veterinary Medical Association, Welfare Implications of Castration of Cattle, (2021). https:\/\/www.avma.org\/KB\/Resources\/LiteratureReviews\/Pages\/castrationcattle-bgnd.aspx (accessed July 13, 2021)."},{"key":"pone.0272169.ref008","unstructured":"Farm animal care manual version 4.0, (2020). https:\/\/nationaldairyfarm.com\/wp-content\/uploads\/2020\/02\/Animal-Care-V4-Manual-Print-Friendly.pdf (accessed July 19, 2021)."},{"key":"pone.0272169.ref009","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3390\/ani8010004","article-title":"Private animal welfare standards\u2014opportunities and risks","volume":"8","author":"F. Lundmark","year":"2018","journal-title":"Animals"},{"key":"pone.0272169.ref010","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/j.1439-0310.2008.01557.x","article-title":"The science of animal suffering","volume":"114","author":"M.S. Dawkins","year":"2008","journal-title":"Ethology"},{"key":"pone.0272169.ref011","doi-asserted-by":"crossref","first-page":"8518","DOI":"10.3168\/jds.2020-18337","article-title":"Behavioral changes in calves 11 days after cautery disbudding: Effect of local anesthesia","volume":"103","author":"S.J.J. Adcock","year":"2020","journal-title":"Journal of Dairy Science"},{"key":"pone.0272169.ref012","first-page":"1993","article-title":"Effects of transdermal flunixin meglumine on pain biomarkers at dehorning in calves1","volume":"95","author":"M.D. Kleinhenz","year":"2017","journal-title":"Journal of Animal Science"},{"key":"pone.0272169.ref013","first-page":"157","article-title":"Prevention and Management of Surgical Pain in Cattle","volume":"29","author":"D.E. Anderson","year":"2013","journal-title":"Veterinary Clinics: Food Animal Practice"},{"key":"pone.0272169.ref014","doi-asserted-by":"crossref","first-page":"10277","DOI":"10.3168\/jds.2019-16630","article-title":"Meloxicam affects the inflammatory responses of bovine mammary epithelial cells","volume":"109","author":"O.W. M. O. Caldeira","year":"2019","journal-title":"J Dairy Sci"},{"key":"pone.0272169.ref015","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.rvsc.2013.01.018","article-title":"A study to compare circulating flunixin, meloxicam and gabapentin concentrations with prostaglandin E2 levels in calves undergoing dehorning","volume":"95","author":"E. Fraccaro","year":"2013","journal-title":"Res Vet Sci"},{"key":"pone.0272169.ref016","first-page":"730","article-title":"Pharmacokinetics and bioequivalence of 2 meloxicam oral dosage formulations in healthy adult horses","volume":"56","author":"M. Vivancos","year":"2015","journal-title":"The Canadian Veterinary Journal"},{"key":"pone.0272169.ref017","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.addr.2018.01.015","article-title":"Polymeric Microneedles for Transdermal Protein Delivery","volume":"127","author":"Y. Ye","year":"2018","journal-title":"Adv. Drug Deliv. Rev"},{"key":"pone.0272169.ref018","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jconrel.2012.01.042","article-title":"Microneedle technologies for (trans)dermal drug and vaccine delivery","volume":"161","author":"K. van der Maaden","year":"2012","journal-title":"Journal of Controlled Release"},{"key":"pone.0272169.ref019","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.biopha.2017.07.019","article-title":"Dissolving microneedles for transdermal drug delivery: Advances and challenges","volume":"93","author":"K. Ita","year":"2017","journal-title":"Biomedicine and Pharmacotherapy"},{"key":"pone.0272169.ref020","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.addr.2012.04.005","article-title":"Microneedles for drug and vaccine delivery","volume":"64","author":"Y.C. Kim","year":"2012","journal-title":"Advanced Drug Delivery Reviews"},{"key":"pone.0272169.ref021","doi-asserted-by":"crossref","first-page":"111544","DOI":"10.1016\/j.msec.2020.111544","article-title":"Design, characterization, and modeling of a chitosan microneedle patch for transdermal delivery of meloxicam as a pain management strategy for use in cattle","volume":"118","author":"D.A. Castilla-Casadiego","year":"2021","journal-title":"Materials Science and Engineering C"},{"key":"pone.0272169.ref022","first-page":"539","article-title":"Pharmacokinetics of single-dose subcutaneous meloxicam injections in black-tailed prairie dogs (cynomys ludovicianus)","volume":"56","author":"T.L. Wright","year":"2017","journal-title":"Journal of the American Association for Laboratory Animal Science"},{"key":"pone.0272169.ref023","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/jvp.12756","article-title":"Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in meat goats","volume":"42","author":"E.J. Reppert","year":"2019","journal-title":"Journal of Veterinary Pharmacology and Therapeutics"},{"key":"pone.0272169.ref024","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0144-8617(00)00288-5","article-title":"Acid hydrolysis of chitosans","volume":"46","author":"K.M. Varum","year":"2001","journal-title":"Carbohydrate Polymers"},{"key":"pone.0272169.ref025","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3390\/md19050236","article-title":"The Kinetics of Chitosan Degradation in Organic Acid Solutions","volume":"19","author":"D. Sikorski","year":"2021","journal-title":"Marine Drugs"},{"key":"pone.0272169.ref026","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1134\/S156009040609017X","article-title":"Degradation of chitosan in solutions in the presence of a redox system","volume":"48","author":"E.N. Fedoseeva","year":"2006","journal-title":"Polymer Science\u2014Series B"},{"key":"pone.0272169.ref027","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1016\/S0032-3861(00)00713-8","article-title":"An infrared investigation in relation with chitin and chitosan characterization","volume":"42","author":"J. Brugnerotto","year":"2001","journal-title":"Polymer (Guildf)"},{"key":"pone.0272169.ref028","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.carbpol.2011.04.038","article-title":"Synthesis, characterization and biological safety of O-carboxymethyl chitosan used to treat Sarcoma 180 tumor","volume":"86","author":"M. Zheng","year":"2011","journal-title":"Carbohydrate Polymers"},{"key":"pone.0272169.ref029","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3390\/polym8090338","article-title":"Preparation of a Novel Chitosan Based Biopolymer Dye and Application in Wood Dyeing","volume":"8","author":"X. Wang","year":"2016","journal-title":"Polymers (Basel)"},{"key":"pone.0272169.ref030","doi-asserted-by":"crossref","first-page":"710","DOI":"10.4103\/0250-474X.84579","article-title":"Effect of Different Carriers on in vitro Permeation of Meloxicam through Rat Skin","volume":"72","author":"M.A. Saleem","year":"2010","journal-title":"Indian J Pharm Sci"},{"key":"pone.0272169.ref031","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1021\/bm301293d","article-title":"Chitosan Microneedle Patches for Sustained Transdermal Delivery of Macromolecules","volume":"13","author":"M.-C. Chen","year":"2012","journal-title":"Biomacromolecules"},{"key":"pone.0272169.ref032","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s12034-012-0313-7","article-title":"PLGA 50:50 nanoparticles of paclitaxel: Development, in vitro anti-tumor activity in BT-549 cells and in vivo evaluation","volume":"35","author":"R.K. Averineni","year":"2012","journal-title":"Bulletin of Materials Science"},{"key":"pone.0272169.ref033","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.biopha.2018.10.078","article-title":"Microneedles: A smart approach and increasing potential for transdermal drug delivery system","volume":"109","author":"T. Waghule","year":"2019","journal-title":"Biomedicine and Pharmacotherapy"},{"key":"pone.0272169.ref034","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0144-8617(99)00127-7","article-title":"Enzymatic degradation of \u03b2-chitin: Susceptibility and the influence of deacetylation","volume":"42","author":"K. Kurita","year":"2000","journal-title":"Carbohydrate Polymers"},{"key":"pone.0272169.ref035","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.3390\/md13041819","article-title":"Stability of chitosan\u2014a challenge for pharmaceutical and biomedical applications","volume":"13","author":"E. Szyma\u0144ska","year":"2015","journal-title":"Mar Drugs"},{"key":"pone.0272169.ref036","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2009.09.004","article-title":"Biodegradation, biodistribution and toxicity of chitosan","volume":"62","author":"T. Kean","year":"2010","journal-title":"Adv Drug Deliv Rev"},{"key":"pone.0272169.ref037","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3390\/vetsci6030073","article-title":"A Comparative Pharmacokinetic Analysis of Oral and Subcutaneous Meloxicam Administered to Postpartum Dairy Cows","volume":"6","author":"D. Shock","year":"2019","journal-title":"Veterinary Sciences"},{"key":"pone.0272169.ref038","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1039\/C4TB01555J","article-title":"Fabrication of a novel partially dissolving polymer microneedle patch for transdermal drug delivery","volume":"3","author":"I.C. Lee","year":"2015","journal-title":"Journal of Materials Chemistry B"},{"key":"pone.0272169.ref039","unstructured":"National Center for Biotechnology Information. PubChem Database, Meloxicam, CID = 54677470, (2020). https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Meloxicam (accessed July 13, 2021)."},{"key":"pone.0272169.ref040","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ejps.2017.04.001","article-title":"Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis","volume":"104","author":"S. Amodwala","year":"2017","journal-title":"European Journal of Pharmaceutical Sciences"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0272169","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T19:02:00Z","timestamp":1659466920000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0272169"}},"subtitle":[],"editor":[{"given":"H\u00e9lder A.","family":"Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0272169","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]}}}